bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatial and temporal expression of fibril‐forming minor collagen genes (types V and XI) during fracture healing
Authors: Yamazaki Masashi , Majeska Robert J. , Yoshioka Hidekatsu , Moriya Hideshige , Einhorn Thomas A.
Published: February 2005

Skeletal development involves the coordinated participation of several types of collagen, including both major and minor fibrillar collagens. Although much is known about the major fibrillar collagens, such as types I and II, less is known about the minor fibrillar collagens, and their role in the repair and regeneration of bone has not been extensively studied. To clarify the role of minor fibrillar collagens in Fracture repair, we examined the spatial and temporal expression of mRNAs for pro‐α2(V) collagen and pro‐α1(XI) collagen in healing fractures in the rat by in situ hybridization and compared their patterns of expression with those Of mRNAs for pro‐α1(I) collagen, pro‐α1(II) collagen, and osteocalcin. A strong signal for pro‐α2(V) was detected in the periosteal osteoprogenitor cells, whereas osteocalcin mRNA was strongly expressed only in the deep layers of the hard callus. The distribution of the pro‐α2(V) signal was correlated with that of pro‐α1(I) but was mutually exclusive of that of pro‐α1(II).The expression of pro‐α1(Xl) mRNA was synchronously regulated with that of pro‐α1(II) during chondrogenesis in the soft callus. In the hard callus, pro‐α1(XI) signal Was found in osteoblastic cells at the site of intramembranous and endochondral ossification. These cells simultaneously expressed pro‐α2(V), although they were negative for pro‐α1(II). These findings suggest that the, α2(V) collagen chain participates in the formation of the noncartilaginous fibrillar network in the hard callus and preferentially contributes to the initial stage of the intramembranous bone formation. Recent reports have, revealed that type‐XI collagen, which had been classified as a cartilage‐type collagen, is not necessarily specific for cartilage. The present results advanced this recognition and demonstrated a coexpression of α1(XI) mRNA and α2(V) mRNA in the noncartilaginous tissues in the fracture callus; this suggests the presence of tissue‐specific and stage‐specific heterotrimers consisting of α1(XI) and α2(V) collagen chains and the association of such hybrid trimers with the major fibrillar collagens in the process of fracture healing.
Physiological and mechanical adaptations of rabbit medial collateral ligament after anterior cruciate ligament transection
Authors: Bray R. C. , Doschak M. R. , Gross T. S. , Zernicke R. F.
Published: February 2005

Progressive physiological and mechanical changes in the medial collateral ligament of the adult rabbit were investigated for as long as 48 weeks after disruption of the anterior cruciate ligament. Eighty‐one New Zealand White rabbits were separated into experimental, sham‐operated control, and normal control groups. The experimental group underwent unilateral transection of the right anterior cruciate ligament, sham‐operated animals served as controls for comparison, and normal animals were evaluated as age‐matched, undisturbed (no surgery) controls. Blood flow to the medial collateral ligament (as a physiological measure) and mechanical function (structural and material properties) were assessed at 6, 14, and 48 weeks. The results indicated that loss of the anterior cruciate ligament leads to early mechanical deterioration of the medial collateral ligament with a corresponding loss of physiological homeostasis. Six to 14 weeks after the transection, values for cross‐sectional area of the medial collateral ligaments rapidly increased to 1.5 times control values. The ligament became twice as large as the control ligament by 48 weeks. Concomitantly, medial collateral ligament stress at failure of the medial collateral ligament complex decreased rapidly 6‐14 weeks after the transection and eventually fell to one‐half that of controls by 48 weeks. In terms of low‐load behaviour, laxity and load relaxation were significantly greater than that of controls 6 weeks after transection and were further increased by 14 weeks. By 48 weeks, laxity values had recovered somewhat and load‐relaxation measures had recovered to near control values. At both 6 and 14 weeks, a statistically significant elevation in blood flow was demonstrated compared with controls. By 48 weeks, however, blood flow was no different from that of the sham‐operated control. Thus, early after transection of the anterior cruciate ligament, both low‐load and high‐load mechanical properties of the medial collateral ligament deteriorated and the rate of blood flow was temporarily elevated. By 48 weeks, blood flow declined to near control values, with a corresponding recovery in viscoelastic behaviour. These findings suggest that, after transection of the anterior cruciate ligament, viscoelastic behaviour of the medial collateral ligament may be related to changes in blood flow and that restoration of normal flow patterns and vascular responses may be linked to tne recovery of some low‐load mechanical properties in the anterior cruciate ligament‐deficient medial collateral ligament.
Exercise of young thoroughbred horses increases impact strength of the third metacarpal bone
Authors: Reilly G. C. , Currey J. D. , Goodship A. E.
Published: February 2005

Exercise can have a profound effect on bone mass but little is known of its effect on bone's material properties. In this experiment, our hypothesis was that a large difference in the training regimen of young thoroughbreds would produce a measurable difference in the mechanical properties of their bone material. When they were about 19 months old, eight thoroughbred racehorses were given one of two exercise regimens that lasted for 19 weeks: four horses (controls) were walked for 40 minutes a day but had no other exercise, and the remaining four (exercised) were additionally trotted for 20 minutes a day and given progressively intensive exercise on a treadmill. Mechanical testing to failure was performed on longitudinal beam specimens of the mid‐diaphysis of the metacarpal. There was no difference in Young's modulus or bending strength between the two groups, although these properties varied somewhat depending on the position within the cortex from which the specimens had come. The specimensfrm the exercised horses had a slightly higher toughness, as measured by work (area under the load‐deformation curve). They had a considerably higher impact strength. The impact strength of specimens from, the outer coitex was also higher than that of those from the inner cortex in both groups. Impact strength correlated positively with the amount of micro‐cracking produced during testing. Microcracking is related to structural and microstructural features in the bone. Increased loading caused the bone to respond in a way lhat enhanced its ability to microcrack and hence its toughness.
Myoblast‐mediated gene transfer to the joint
Authors: Day Charles S. , Kasemkijwattana Channarong , Menetrey Jacques , Floyd S. Steven , Booth David , Moreland Morey S. , Fu Freddie H. , Huard Johnny
Published: February 2005

Several genetic and acquired pathologic conditions of the musculoskeletal system, such as arthritis and damage to ligament, cartilage, and meniscus, may be amenable to gene therapy. Even though ex vivo gene transfer with synovial cells has been shown to deliver genes encoding for anti‐arthritic proteins into the rabbit knee joint, its success has been limited by a transient transgene expression, In this study, data were investigated regarding the use of muscle cells as an alternative gene‐delivery vehicle to the joint in newborn rabbit and adult severe combined immunodeficiency mice. We demonstrated that myoblasts were transduced more efficiently than synovial cells with use of the same adenoviral preparation in vitro. After intra‐articular injection, the engineered muscle cells adhered to several structures in the joint, including the ligament, capsule, and synovium. In addition, myoblasts fused to form many post‐mitotic myotubes and myofibers at different locations of the joint of the newborn rabbit 5 days after the injection. In the knee of the adult mouse, myoblasts fused and expressed the reporter gene for at least 35 days after the injection. The presence of post‐mitotic myofibers in the knee joint raises the possibility of long‐term expression of the secreted protein. Currently, numerous tissues in the joint (ligament, meniscus, and cartilage) have poor intrinsic healing capacity and frequently need surgical corrections. A stable gene‐delivery vehicle to the joint producing proteins that ameliorate these different musculoskeletal conditions may change the clinical implications of these pathologies.
Evaluation of a bone's in vivo 24‐hour loading history for physical exercise compared with background loading
Authors: Koniecynski D. D. , Truty M. J. , Biewener A. A.
Published: February 2005

The present study sought to answer two research questions. First, how distinctive, as a potential osteogenic stimulus, are short‐duration bouts of treadmill exercise relative to sedentary background activity? Second, how well does daily effective strain stimulus relate the loading history for one such exercise program, in comparison with other experimental loading programs, to bone formation? In vivo cortical strains were measured in the tibiotarsus of White Leghorn chickens at a late stage of skeletal growth (14–34 weeks old) under the conditions of a previous investigation of bone formation in response to an exercise program (15 min/day, treadmill gait at 60% maximum speed while carrying 20% body mass) that included sedentary background activity. These strain data were compiled into 24‐hour loading histories of peak cyclic strain, demonstrating that strains were statistically different for exercise and background activities (p < 0.0001), with both the magnitude and number of cyclic strain events being greater during exercise (generally greater than 500 microstrain, 2,500 cycles/day) than during background activity (generally less than 500 microstrain, mean: 775 cycles/day). Strains during exercise accounted for more than 97% of the daily effective strain stimulus for bone adaptation, despite the fact that exercise comprised only 1% of the daily period (15 min/day). The levels of the daily effective strain stimulus were similar to those calculated for strains engendered by artificial loading of functionally isolated avian ulnae, which either maintained bone mass or resulted in a 15% increase of cortical cross‐sectional area in both sets of studies. These results indicate that short‐duration bouts of treadmill exercise and sedentary background activity can represent distinct osteogenic stimuli for adaptive bone modeling. They also provide experimental support for the use of a daily effective strain stimulus to quantify skeletal loading histories for differing programs of physical exercise, although the relative importance of other mechanical and nonmechanical factors requires further investigation.
Mechanical behavior of human morselized cancellous bone in triaxial compression testing
Authors: Brodt Michael D. , Swan Colby C. , Brown Thomas D.
Published: February 2005

Despite its widespread use as graft material in orthopaedic surgical procedures, morselized cancellous bone has not yet been well characterized from the standpoint of its mechanical properties. To accommodate the noncohesive nature of this loose particulate form of bone, a triaxial compression test apparatus commonly used in engineering soil mechanics was adapted for the testing of fresh‐frozen human morselized cancellous bone specimens. Triaxial compression tests were run to 30% axial strain at five different levels of confining pressure ranging from 0.276 to 0.552 MPa. The measured axial stress versus axial strain behavior was bimodal, characterized initially by relatively stiff linear behavior, then by a rapid transition to a much more compliant (but, again, approximately linear) domain until test cessation. The apparent axial moduli of both response regions were found to be nearly linear functions of the transverse confining pressure. As typically prepared surgically, the distribution of particle size was found to have approximately 80% of the bone graft, by weight, encompassed in particles 0.42–3.2 mm in size. Triaxial tests of samples segregated by size showed that particle size had no appreciable effect on apparent material properties. The nominal Young's modulus and Poisson's ratio of morselized cancellous bone were 100 MPa and 0.2, respectively.
Biomechanical characterization of osseointegration: An experimental in vivo investigation in the beagle dog
Authors: Brånemark Rickard , Öhrnell Lars‐Olof , Skalak Richard , Carlsson Lars , Brånemark Per‐Ingvar
Published: February 2005

This study reports the results of torsion tests, pull‐out tests, and lateral Ioading tests on osseointegrated commercially pure titanium fixtures. The tests were performed in vivo on six beagie dogs. Three fixtures, each with a diameter of 3.7mm, were installed bilaterally in the tibia of each animal. The mean maximal pull‐out load was 1.55 kN (n = 4) the mean maximal lateral transverse load was 0.21 kN (n = 2), the mean maximal lateral axial load was (0.18 kN (n = 2)) the mean breakpoint torque was 0.31 Nm (n = 3), and the mean maximal torque was 0.43 Nm (n = 3). The torsion test revealed an almost immediate plastic deformation of the interface between the implant and bone: this indicates that although the contact between the bone and the implant is close, there is no strong bond, at least not in shear. The major transfer of load from the implant to the surrounding bone tissue must therefore depend on the design of the implant. A histological evaluation with measurements of the amount of bone in contact with the fixtures was performed. By the use of the histological and mechanical data, it is possible to estimate shear stresses in bone tissue (pull‐out test) and in the interface (torque test), The mean maximal shear stress in bone tissue in the pull‐out tests was 100 MPa (n = 4); the mean shear stress in the interface was 4.3 MPa (n = 3) in the torsion tests at the breakpoint torque and was 6.0 MPa (n = 3) at the maximal torque. It was also possible to estimate the shear modulus of elasticity in the pull‐out and torque tests. The mean shear modulus in pull‐out was 119 MPa (n = 4), and the mean apparent shear modulus in torsion was 9 kPa (n = 3) for an assumed interface thickness of 100 nm and was 86 kPa (n = 3) for an assumed interface thickness of 1.000 nm.
Dye incorporation to enhance the laser ablation of standard and reduced‐modulus bone cements
Authors: Lee Chi L. , Litsky Alan S. , Roberts Cynthia J.
Published: February 2005

Laser ablation of acrylic bone cement is an alternative method of cement removal that can be used during revision arthroplasty of cemented implants. This study investigated the feasibility of using a continuous‐wave Argon ion laser (wavelength = 514 nm) with the addition of methylene blue or red dye no. 13 to enhance the ablation of two types of bone cements: polymethylmethacrylate and polybutylmethylmethacrylate. Six cement/dye combinations were studied while power (0.5, 0.75, and 1.0 W) and exposure times (30, 45, 60, and 90 seconds) were varied. The Argon laser was unable to ablafre undyed polymethylmethacrylate or polybutylmethylmethacrylate. However, ablation was shown for both cements with either dye. The red dye had a stronger absorption peak at 514 nm than did the blue dye. Statistically larger ablation areas were seen for red polymethylmethacrylate than for blue polymethylmethacrylate (p < 0.013) at all levels tested. Ablation areas were larger in red than in blue polybutylmethylmethacrylate cement. Blue polybutylmethylmethacrylate cement produced larger ablation areas than did blue polymethylmethacrylate cements at all energy levels tested, with smaller surrounding damage areas. Red polybutylmethylmethacrylate cement also produced larger ablation areas than did red polymethylmethacrylate cement (at 0.75 and 1.0 W), again with smaller damage areas. Damage zones were smallest in red polybutylmethylmethacrylate cements at all test levels. These results suggest that, by using dyes to selectively alter the absorption characteristics of bone cement, laser ablation can be an effective method for cement removal. Changes in the chemical structure of the cement can also influence the response to laser treatment. Furthermore, the absorption spectra of the bone cement can be altered to maximize energy absorption at a wavelength that is not absorbed by bone tissue; this potentially minimizes damage to bone during revision surgery.
Quantitative study of the quadriceps muscles and trochlear groove geometry related to instability of the patellofemoral joint
Authors: Farahmand Farzam , Sejiavongse Wongwit , Amis Andrew A.
Published: February 2005

This was a quantitative study of the major anatomical structures associated with instability of the patellofemoral joint: the quadriceps muscles and the femoral trochlear groove. The attachments of the muscles to the patella, their lines of action, and their relative sizes (physiological cross‐sectional areas) were found. On the basis of the physiological cross‐sectional areas, it was estimated that the central muscles—the rectus femoris and vastus intermedius—contributed 35% of the quadriceps strength, with 40% from the vastus lateralis and 25% from the vastus medialis. The vastus lateralis had the most variable results, with the ratio of the lateralis to the medialis ranging from 0.90 to 2.18; this may be associated with patellar instability. Both the long and oblique parts of the vastus medialis were more oblique than the corresponding parts of the vastus lateralis. Photographic “skyline” views of the trochlear groove produced data on the sulcus angle and ratio of depth to width. The data showed that the trochlear groove did not deepen in the area contacted by the patella with progressive knee flexion (p > 0.53). contrary to popular belief. These data are useful for objective analysis of patellofemoral stability and related surgical interventions.
Fatigue of bone and bones: An analysis based on stressed volume
Authors: Taylor David
Published: February 2005

The measured fatigue strength of a material can be affected by specimen size: tests using a large stressed volume may show a low fatigue strength due to the increased probability of finding weak regions. A Weibull analysis revealed an important size effect in bone and predicted this effect with an accuracy of 12%. This approach also explained apparent inconsistencies in the published data and made it possible to separate and quantify the effects of frequency, loading mode, and material source. The effect of frequency is the same for human and bovine bone, and the differences between different types of loading (tension, compression, and bending) are small (maximum: 12%). By extrapolating to the volume of whole bones, it is concluded that large bones will have a fatigue strength much lower, by a factor of 2–3, than that measured by conventional tests. Failure within 105 cycles is expected to occur at cyclic stresses of 23–30 MPa in human long bones and of 32–43 MPa in bovine bones. Repair is therefore needed to prevent failure at physiological stress levels.
Effect of cooling on cutaneous microvascular adrenoceptors in vivo in the rabbit ear
Authors: Li Zhongyu , Koman L. Andrew , Rosencrance Eileen , Pollock David C. , Smith Beth P. , Strandhoy Jack W. , Smith Thomas L.
Published: February 2005

Previous studies have suggested that moderate cooling increases the responsiveness of vascular α2‐adrenoceptors. However, limited information is available documenting the influence of temperature changes on adrenoceptor responses in the microvasculature of thermoregulatory organs (e.g., the human digit and the rabbit ear) subjected to a wide range of temperatures. In the present study, the effect of local cooling (24°C) on cutaneous microvascular adrenoceptors in the ear was observed in vivo in male New Zealand White rabbits (total: 66 ears). The rabbit ear was studied in a temperature‐controlled tissue bath; the ear preparation was pretreated with terazosin (an α1‐adrenoceptor antagonist) (10−5 M) or a combination of terazosin (10−5 M) and propranolol (a β‐adrenoceptor antagonist) (10−6 M). The microvascular diameter responses of the ear to norepinephrine (10−l1‐10−4M) then were determined at 24 or 34°C, respectively, to determine the influences of low temperature on adrenoceptor responses to norepinephrine stimulation. The results demonstrated that low concentrations of norepinephrine induced vasodilation in arterioles and arteriovenous anastomoses. This vasodilation was followed by vasoconstriction with an increased concentration of norepinephrine in animals with α1‐adrenergic blockade at 34°C. Moderate tissue cooling increased the microvascular maximal response of the rabbit ear to norepinephrine and abolished the vasodilatation induced by a low concentration of norepinephrine. There was no significant difference in the microvascular response to norepinephrine between the two temperature conditions after simultaneous blockade of α1‐adrenoceptors and β‐adrenoceptors. Data from the present study indicate that moderate cooling does not enhance the responsiveness of α2‐adrenoceptors to norepinephrine. In contrast, cooling reduced the β‐adrenergic activity of arterioles and arteriovenous anastomoses after norepinephrine stimulation.
In vitro and In vivo study on the effect of autogenous cancellous bone and intramedullary polymethylmethacrylate on allograft construct strength
Authors: Hanson Peter D. , Warner Chad , Frassica Frank J. , Vanderby Ray , Markel Mark D.
Published: February 2005

An in vitro study was performed to compare the effects of augmenting interlocking nails of one of two diameter (5 or 6 mm) with intramedullary polymethylmethacrylate. Subsequently, an in vivo study was performed to compare the effects of augmenting the interlocking nail with five combinations of intramedullary polymethylmethacrylate and autogenous cancellous bone applied to the periosteal surface or within the medullary canal. Dogs were killed 6 months after the procedure for biomechanical evaluation of the femora in axial compression, mediolateral and craniocaudal bending, and torsion. Results from the in vitrostudy at the proximal osteotomy indicated the 6‐mm inteilocking nail with intramedullary polymethylmethacrylate had greater stiffness than the 5‐mm interlocking nail without it (p < 0.05). At the distal osteotomy, regardless of the diameter of the interlocking nail, the addition of intramedullary polymethylmethacrylate increased stiffness (p < 0.05). Results from the in vivo study indicated greater global construct stiffness with an interlocking nail alone, an interlocking nail augmented with intramedullary polymethylmethacrylate and cancellous bone at the periosteal surface, and an interlocking nail augmented with cancellous bone within the medullary canal and at the periosteal surface (p < 0.05). At the osteotomy level, the interlocking nail augmented with intramedullary polymethylmethacrylate and cancellous bone at the periosteal surface had greater stiffness than did an interlocking nail alone or an interlocking nail augmented with either intramedullary polymethylmethacrylate. cancellous bone within the medullary canal, or cancellous bone at the periosteal surface (p < 0.05) but produced the same results as an interlocking nail augmented with cancellous bone within the medullary canal and at the periosteal surface. The results suggest that augmenting interlocking nail fixation with intramedullary polymethylmethacrylate by itself offers no advantage but that acombination of intramedullary polymethylmethacrylate and cancellous bone at the periosteal surface improves structural properties at 6 months.
Actions of endothelin‐1,2, and 3 in the microvasculature of bone
Authors: Briggs Peter J. , Moran Christopher G. , Wood Michael B.
Published: February 2005

Endothelins have recently been associated with hypoxia‐related vascular smooth‐muscle constriction and with the so‐called no‐reflow phenomenon following reperfusion. Their action is tissue dependent. The role of endothelins on vascular smooth muscle in bone is unknown. An ex vivo perfusion model was used to investigate the effects of the three different endothelins on the vascular resistance in the canine tibia. Endothelin‐1 and endothelin‐2 had molar potencies similar to that of norepinephrine, whereas endothelin‐3 was less potent. Tachyphylaxis to the same dose of endothelin‐1 did not occur. The calcium channel blocker, diltiazem, attenuated (45% reduction) the vasoconstrictor responses to norepinephrine (p < 0.005) but had a smaller effect (24% reduction) on the responses to endothelin (p < 0.025). Vascular smooth muscle in bone appears to have endothelin receptors that are similar to those in other organs.
Semiquantitative reverse transcription‐polymerase chain reaction analysis of mRNA for growth factors and growth factor receptors from normal and healing rabbit medial collateral ligament tissue
Authors: Sciore Paul , Boykiw Raymond , Hart David A.
Published: February 2005

Growth factors and their receptors play an essential role in the development, maturation, and response to injury of all tissues. A number of studies have explored the possibility of improving ligament healing with exogenous growth factors. However, limited data is available regarding the endogenous growth factor network in ligaments on which any exogenous growth factors must impact. The purpose of this study was to assess the endogenous growth factor network with molecular techniques. By the sensitive reverse transcription‐polymerase chain reaction technique, transcripts for a number of growth factors and receptors were detected with RNA isolated from normal and healing rabbit medial collateral ligament tissues. These include transforming growth factor‐β1, insulin‐like growth factors I and II, basic fibroblast growth factor, endothelin‐1, and the receptors for insulin and insulin‐like growth factor II. Semiquantitative reverse transcription‐polymerase chain reaction analysis of RNA from normal and scar tissues from the medial collateral ligament revealed that the levels of several transcripts were elevated in the scar tissue. It was not possible to confirm biological activity because of the hypocellularity of the tissues; however, the results, obtained indicate that the reverse transcription‐polymerase chain reaction approach to defining the endogenous growth factor‐receptor phenotype is feasible, and further definition should contribute to the development of rational approaches to exogenous therapy to improve healing.
In situ calibration of miniature sensors implanted into the anterior cruciate ligament. Part I: Strain measurements
Authors: Markolf Keith L. , Willems Matthew J. , Jackson Steven R. , Finerman Gerald A. M.
Published: February 2005

The goals of this study were to (a) evaluate the differential variable reluctance transducer as an instrument for measuring tissue strain in the anteromedial band of the anterior crudciate ligament, (b) develop a series of calibration curves (for simple states of knee loading) from which resultant force in the ligament could be estimated from measured strain levels in the anteromedial band of the ligament, and (c) study the effects of knee flexion angle and mode of applied loading on ouput from the transducer. Thirteen fresh‐frozen cadaveric knee specimens underwent mechanical isolation of a bone cap containing the tibial insertion of the anterior cruciate ligament and attachment of a load cell to measure resultant force in the ligament. The transducer (with barbed prongs) was inserted into the anteromedial band of the anterior cruciate ligament to record local elongation of the instrumented fibers as resultant force was generated in the ligament. A series of calibration curves (anteromedial bundle strain versus resultant force in the anterior cruciate ligament) were determined at selected knee flexion angles as external loads were applied to the knee. During passive knee extension, strain readings did not always follow the pattern of resultant force in the ligament; erratic strain readings were often measured beyond 20° of flexion, where the anteromedial band was slack. For anterior tibial loading, the anteromedial band was a more active contributor to resultant ligament force beyond 45° of flexion and was less active near full extension; mean resultant forces in the range of 150–200 N produced strain levels on the order of 3–4%. The anteromedial band was also active during application of internal tibial torque; mean resultant forces on the order of 180–220 N produced strains on the order of 2%. Resultant forces generated by varus moment were relatively low, and the anteromedial band was not always strained. Mean coefficients of variation for resultant force in the ligament (five repeated measurements) ranged between 0.038 and 0.111. Mean coefficients of variation for five repeated placements of the strain transducer in the same site ranged from 0.209 to 0.342. Insertion and removal of this transducer at the anteromedial band produced observable damage to the ligament. In our study, repeatable measurements were possible only if both prongs of the transducer were sutured to the ligament fibers.
Mechanical properties of wrist extensor tendons are altered by the presence of rheumatoid arthritis
Authors: Breault‐Janicki Martine J. , Small Carolyn F. , Bryant J. Timothy , Dwosh Isaac L. , Lee J. Michael , Pichora David R.
Published: February 2005

The in vitro mechanical properties of 14 wrist extensor tendons salvaged at surgery from patients with inflammatory (rheumatoid) arthritis and noninflammatory arthrosis were measured in uniaxial tension and compared. The rheumatoid tendons had higher extensibility at low stresses, lower stiffness in the linear portion of the stress‐strain curve, greater rates of stress relaxation, and lower ultimate strengths than did the nonrheumatoid tendons. Differences in tangent modulus, stress remaining at 100 seconds, and ultimate tensile strength were significant at the 95% confidence level. In vivo, mechanically, impaired tendons may play an important role in destabilization of the wrist in patients with rheumatoid arthritis.
Local tissue properties in bone healing: Influence of size and stability of the osteotomy gap
Authors: Augat Peter , Margevicius Kristen , Simon Jörg , Wolf Steffen , Suger Gebhard , Claes Lutz
Published: February 2005

To characterize the site‐specific mechanical and histological properties in fracture repair and to relate these properties to the initial mechanical situation, an experimental fracture model was used in the metatarsus of 42 sheep. the mechanical situation of a transverse osteotomy was described by three gap sizes (1,2, or 6 mm) and two amounts of strain (7 or 31 %). An external fixator that allowed a defined axial movement provided control of these settings. Nine weeks following surgery, the healing area was dissected and tensile and compressive properties were measured in subregions of the fracture gap and the periosteal callus. The central, sagittal section was used for quantitative histology. We found the quality of the tissue along the osteotomy line to be most important for regaining mechanical stability. Increasing the size of osteotomy gaps resulted in poorer mechanical and histological qualities, and the repair process was less complete. Interfragmentary strain did not significantly influence the repair process. The smaller strain levels had already stimulated the secondary repair process, and this stimulatory effect could not be further enhanced by increasing the amount of strain. Our finding that large gaps between bone segments were not as well healed as were smaller gaps suggests that it is advantageous to avoid large gaps in fracture treatment.
Effects of injurious compression on matrix turnover around individual cells in calf articular cartilage explants
Authors: Quinn Thomas M. , Grodzinsky Alan J. , Hunziker Ernst B. , Sandy John D.
Published: February 2005

The effects of mechanical injury on the metabolism of cartilage matrix are of interest for understanding the pathogenesis of osteoarthrosis and the development of strategies for cartilage repair. The purpose of the present study was to examine the effects of injury on matrix turnover in a calf articular cartilage explant system for which the effects of mechanical loading on cell activity and the cell‐mediated pathways of matrix metabolism are already well characterized. New methods of quantitative autoradiography were used in combination with established biochemical and biomechanical techniques for the analysis of cell and matrix responses to acute mechanical injury, with particular attention to the processes of localized matrix turnover in the cell‐associated matrices of individual chondrocytes. Matrix deposition and turnover around cells in control explants was spatially dependent, with the highest rates of proteoglycan deposition and tunrtover arid the lowest rates of collagen deposition (as indicated by [3H]proline autoradiography) occurring in the pericellular matrix. Injurious compression was associated with (a) an abrupt decrease in the tensile load‐carrying capacity of the collagen matrix, apparently associated with mechanical failure of the tissue, (b) a considerable but subtotal decrease in cell viability, marked by the emergence of an apparently inactive cell population interspersed within catabolically active but abnormally large cells, and (c) sustained, elevated rates of protcoglycan turnover, particularly in the cell‐associated matrices of apparently viable cells, which involved the increased release of aggregating species in addition to a spectrum of degradation fragments that were also in controls. These results may represent an in vitro model for the responses of chondrocytes and the cartilage extracellular matrix to mechanical injury.
Effect of ciprofloxacin on the proliferation of osteoblast‐like MG‐63 human osteosarcoma cells in vitro
Authors: Miclau Theodore , Edin Matthew L. , Lester Gayle E. , Lindsey Ronald W. , Dahners Laurence E.
Published: February 2005

Locally applied antibiotic therapy is gaining popularity for the treatment of infections associated with open fractures and posttraumatic osteomyelitis. With use of local techniques, ciprofloxacin levels as high as 1,300 μg/ml. or over 200 times the bone levels achieved with intravenous administration, have been reported. To study the possible effects of ciprofloxacin on bone, osteoblast‐like cells from the MG‐63 human osteosarcoma cell line were studied. The cells were grown in antibiotic‐free media and exposed to concentrations of ciprofloxacin at 0, 10, 100, 200, and 1,000 μg/ml to establish an initial dose‐response curve. Media containing the appropriate dose of ciprofloxacin were changed every 24 hours. Cell number and [3H]thymidine incorporation per cell were determined at 0, 24 and 72 hours. A second dose‐response curve was performed at concentrations of 0, 10, 20, 40, and 80 μg/ ml. Three experiments, each with four observations, were performed. The results of this study demonstrated that ciprofloxacin caused significant decreases (p < 0.05) in cell number at 40 μg/ml at 24 hours and 20 μg/ml at 72 hours. [3H]thymidine incorporation per cell decreased significantly at levels of 80 μg/ml at 24 hours and 20 μg/ml at 72 hours. The authors conclude that reported local levels of ciprofloxacin seen in vivo inhibit the proliferation of human osteoblast‐like cells in vitro.
Expression of cartilage extracellular matrix and potential regulatory genes in a new human chondrosarcoma cell line
Authors: Chansky Howard , Robbins James R. , Cha Steven , Raskind Wendy H. , Conrad Ernest U. , Sandell Linda J.
Published: February 2005

A human chondrosarcoma cell line has been established from an aggressive chondrosarcoma. The cells grow in a monolayer culture (doubling time: 2 days) and form aggregates. The aggregates consist of a rim of cells surrounding a hollow core. The cell line exhibits a unique pattern of mRNA expression with several molecules characteristic of the chondrocyte phenotype. Consistent with the chondrocyte phenotype, mRNAsencoding types IX and XI collagens were present along with an abundant expression of mRNAsencoding the core protein of the cartilage proteoglycans biglycan and aggrecan. No expression of mRNAs encoding types I or II fibrillar collagens or the proteoglycan decorin was observed. Sodium dodecyl sulfate‐polyacrylamide gel electrophoretic analysis of [35S]sulfate‐radiolabeled material confirmed the translation of proteoglycans containing glycosaminoglycan chains. The expression of molecules that contribute to cartilage development and tumorigenesis was examined. The cell line produces abundant mRNA that encodes transforming growth factor‐β1, a member of a family of cartilage and bone inductive proteins. The expression of mRNA encoding two proteins associated specifically with chondrogenesis was detected: Cart‐1, a homeobox protein involved in cartilage differentiation, and CD‐RAP, a secreted molecule restricted under normal conditions to differentiating chondrocytes and cartilage. Overexpression of p53, a tumor‐suppressor gene, was detected. DNA analysis revealed a loss of heterozygosity at the chromosomal locus encoding p53, with the deletion of one p53 allele and the mutation of the remaining allele in both the parent tumor and the cell line. The malignant chondrosarcoma phenotype may be related to the unique gene expression pattern that is characteristic in many ways of differentiating chondroblasts, as well as to the inactivation of the p53 function that could contribute to the proliferative capacity of the cell line. This cell line may serve as a biological model for further investigation of the etiology of human chondrosarcomas and for the synthesis and regulation of cartilage‐specific genes.
Deformation of femoral nails with intramedullary insertion
Authors: Krettek Christian , Mannß Jürgen , Miclau Theodore , Schandelmaier Peter , Linnemann Ina , Tscherne Harald
Published: February 2005

Current methods of distal interlocking of intramedullary femoral nails are dependent on image intensification. However, radiation exposure to the patient, the operating room staff, and the surgeon remains a concern. Proximally mounted, radiation‐free aiming systems for distal interlocking of femoral nails have reportedly failed because of nail deformation with insertion. To better understand this deformation, a threedimensional magnetic motion tracking system was used to determine the position of the distal interlocking hole following nail insertion. The amount and direction of deformation of commercially available smalldiameter implants (unslotted 9‐mm nails inserted without reaming) and large‐diameter implants (slotted 13‐mm nails inserted with reaming) from a single manufacturer were analyzed. Measurements of deformation (three translations and three angles), based on the center of the distal transverse locking hole, were performed on 10 paired intact human cadaveric femora before and after insertion. The technique produced the following results for the small and large‐diameter nails, respectively: lateral translations of 18.1 ± 10.0 mm (mean ± SD, range: 47.8 mm) and 21.5 ± 7.9 mm (range: 26.4 mm), dorsal translations of ‐3.1 ± 4.3 mm (range: 15.2 mm) and 0.4 ± 9.8 mm (range: 30.1 mm), and rotation about the longitudinal axes of −0.1 ± 0.2° (range: 0.7°) and 10.0 ±3.1° (range: 7.8°). This technique is useful for measuring insertion‐related femoral nail deformation. The data for the nails tested suggest that a simple aiming arm, mounted on the proximal end of the femoral nail alone, will not sufficiently provide accurate distal aiming.
Quadriceps load aggravates and roofplasty mitigates active impingement of anterior cruciate ligament grafts against the intercondylar roof
Authors: Goss Ben C. , Howell Stephen M. , Hull M. L.
Published: February 2005

Because of the complications of impingement of anterior cruciate ligament grafts on the intercondylar roof and because current surgical procedures locate the tibial tunnel such that impingement is avoided during passive but not active extension, the objectives of this study were to determine if (a) active extension precipitates and aggravates roof impingement, and (b) a roofplasty mitigates the effects of impingement. The tibial translation, flexion angle defining the onset of roof impingement, graft‐roof contact pressure, and graft tension were measured for six cadaveric specimens. In each specimen, two tibial tunnel positions were studied: one customized for the slope of the intercondylar roof, and the other translated 6 mm anteriorly from the customized position. For a quadriceps load of 1,500 N, the flexion angle defining the onset of impingement, the peak contact pressure, and the graft tension increased significantly for both tunnel positions. The increases occurred because of the anterior tibial translation caused by the active load. Although a roofplasty decreased the onset of the angle of impingement, the graft tension remained unaffected. Thus, to mitigate the effect of impingement during active rehabilitative knee extension exercises, the position of the tibial tunnel must be customized to the angle of the intercondylar roof and a roofplasty must be performed. The extent of bone removed must be customized as well and can be determined by removing bone from the intercondylar roof in excess of that required to freely pass a rod. the same diameter of the graft, through the tibial tunnel into the intercondylar notch with the knee in full passive extension.
Increased substance P in subacromial bursa and shoulder pain in rotator cuff diseases
Authors: Gotoh Masafumi , Hamada Kazutoshi , Yamakawa Hideyuki , Inoue Akio , Fukuda Hiroaki
Published: February 2005

The subacromial bursa is recognized as a site associated with the shoulder pain caused by rotator cuff disease in the middle‐aged and elderly. Substance P is contained in primary afferent nerves, and its quantity increases during chronic pain. The amount of substance P in the subacromial bursa of patients with rotator cuff disease was examined. Radioimmunoassay and immunohistochemistry were employed to quantify and localize substance P. The preoperative pain level was measured with a visual analogue scale with 0 as no pain. 5 as moderate, and 10 as severe. Thirty‐seven patients that had undergone operation were divided into two groups: one composed of 19 patients with subacromial bursitis and a partial‐thickness tear of the rotator cuff (nonperforated cuff) and the other composed of 18 patients with a full‐thickness tear (perforated cuff). Subacromial bursae obtained from seven fresh cadavers with no shoulder pain before death were used as controls. The visual analogue scale showed significantly greater pain in the group with the nonperforated rotator cuff than in the group with the perforated cuff. Consistent with these results, the amount of substance P in the subacromial bursa was significantly greater in the former group than in the latter. Nerve fibers immunoreactive to substance P were localized around the vessels, with a larger number of fibers in the group with the nonperforated rotator cuff. Therefore, an increased amount of substance P in the subacromial bursa appears to correlate with the pain caused by rotator cuff disease.
Osteoclasts are required for bone tumors to grow and destroy bone
Authors: Clohisy Denis R. , Ramnaraine Margaret L.
Published: February 2005

It has been hypothesized that bone resorption during tumor osteolysis is performed by osteoclasts. Data supporting this hypothesis have been provided from analysis of human biopsy specimens obtained from sites of tumor osteolysis, as well as from experimentation with in vivo animal models. Experiments in this report take this concept one step further by testing the hypothesis that osteoclasts are required for bone tumors to grow and destroy bone. To test this hypothesis, the influence of an osteolytic sarcoma tumor, NCTC clone 2472 (2472). on bone was studied in animals that are osteoclast deficient (microphthalmic, strain B6C3Fe‐a/a‐Mitfmi) but whose osteoclast deficiency can be reversed following bone marrow transplantation. Femora of these mice and unaffected wild‐type siblings were injected with 105 2472 cells, and after 14 days the femora were analyzed by radiographic and histomorphometric analysis. Macroscopic tumor, tumor‐induced osteolysis, and increased osteoclast number were noted in femora of normal mice but not in femora of osteoclast‐deficient mice (p < 0.001). Bone marrow transplantation converted osteoclast‐deficient mice to mice with femora that contained osteoclasts in 4 weeks. Femora of these mice were then injected with 105 2472 tumor cells; after 14 days, in contrast to the findings in the original osteoclast‐deficient mice, macroscopic tumor was present, tumor‐induced osteolysis was noted on roentgenograms, and osteoclast number was increased when tumor‐bearing limbs were compared with sham‐injected limbs (p < 0.001). These data prove the hypothesis that osteoclasts are required for 2472 tumor‐induced osteolysis, and they introduce the exciting possibility that osteoclasts are also required for tumors to grow in bone.
Up‐regulation of inducible nitric oxide synthase and production of nitric oxide by the swarm rat and human chondrosarcoma
Authors: Cesare Paul E. Di , Carlson Cathy S. , Attur Mukundan , Kale Ashay A. , Abramson Steven B. , Valle Craig Delia , Steiner German , Amin Ashok R.
Published: February 2005

Production of nitric oxide by solid tumors may have important ramifications regarding tumor growth and potential metastasis. This study demonstrated that the chondrosarcoma of the Swarm rat has upregulated mRNA for inducible nitric oxide synthase and produces nitric oxide. These results were confirmed by (a) the, presence of a 4.4‐kb band of mRNA detected by Northern blot using a probe for inducible nitric oxide synthase, (b) a 133‐kDa band of prothein that was detected with either a polyclonal or monoclonal antibody to the inducible nitric oxide synthase of the murine macrophage. and (c) the detection of nitrites from the culture medium of freshly cultured, isolated chondrosarcoma cells. This study showed that the expression of inducible nitric oxide synthase and the production of nitric oxide by the tumor can be increased by stimulation with endotoxin lipopolysaccharide and can be inhibited by inducible nitric oxide synthase inhibitors (L‐N(g)‐monomethyl arginine and aminoguanidine). Immunostaining confirmed the presence of inducible nitric oxide synthase within the tumor cells and appeared to localize the enzyme to the cytoplasm of the cells. A human chondrosarcoma was also shown to have an upregulated inducible nitric oxide synthase by both the detection of mRNA for inducible nitric oxide synthase and the presence of nitrites from the culture medium of the tumor in organ culture. Because the chondrosarcoma of the Swarm rat is a well differentiated solid tumor that rarely metas‐tasizes, nitric oxide may be produced by the tumor to promote local growth by effects on vascular supply.