bluuebunny/crossref_metadata_2025_split huggingface dataset:
Initial evidence for the involvement of bone morphogenetic protein‐2 early during periosteal chondrogenesis
Authors: Sanyal Arunik , Sarkar Gobinda , Saris Daniel B. F. , Fitzsimmons James S. , Bolander Mark E. , O'Driscoll Shawn W. 
Published: February 2005

AbstractThe potential of periosteum to form cartilage makes periosteal transplantation a viable approach to repairing defects in articular cartilage, which has a limited potential for repair. However, cartilage repair, including that by periosteal chondrogenesis, is poorly understood. Consequently, a thorough understanding of its molecular mechanisms will help to achieve the quality of neocartilage required for its clinical application in damaged joints. An in vitro model was used to study the early molecular events of periosteal chondrogenesis. During the search for the expression of transforming growth factor‐β‐related mRNAs in this model system, bone morphogenetic protein‐2 mRNA expression was found to be upregulated 20‐fold within the first 12 hours of culture. This stimulation was dependent on the explants being suspended in agarose and did not occur with explants cultured in liquid medium. The upregulation of bone morphogenetic protein‐2 mRNA expression was also enhanced by exogenously added transforming growth factor‐β in the presence of fetal calf serum. The upregulation, however, was not transient; rather, it persisted over a prolonged period in both transforming growth factor‐β‐treated and untreated explants. Further data indicate that this stimulation of bone morphogenetic protein‐2 mRNA expression was regulated at the transcriptional level and that no new protein synthesis was required for this. Bone morphogenetic protein‐2 is known to influence developmental chondrogenesis; therefore, these observations direct our attention toward an important potential role of it as a regulator of the early events in cartilage repair. Furthermore, because periosteum produces fracture (cartilage) callus, these findings may be important in defining the molecular mechanisms of fracture healing.
Relationship between body mass index and activity in hip or knee arthroplasty patients
Authors: McClung Christian D. , Zahiri Christopher A. , Higa Jerilyn K. , Amstutz Harlan C. , Schmalzried Thomas P. 
Published: February 2005

AbstractThe weight of patients has not been demonstrated to have a consistent effect on the rate of polyethylene wear in clinical studies of total joint replacement. For this reason, we analyzed the relationship beetween quantitative activity, measured with a pedometer, and body mass index, a measure of obesity. Data were acquired for 209 individuals, 22‐82 years of age; all were independent community walkers. One hundred and fifty‐one had a well functioning total hip or knee replacement. Analysis of variance was used to evaluate the relationship between activity and body mass index, with adjustments for confounding variables. The 58 individuals with no total joint prosthesis averaged 7,781 steps per day, which was higher (p < 0.01) than those with a total hip (5,869 steps per day) or knee (4,597 steps per day) replacement. The subjects with no total joint prosthesis were, however, younger than the patients with a prosthesis (p < 0.01), and the body mass index of the patients with a total knee replacement was higher than that of the patients with a hip replacement and that of the subjects with no prosthesis (p < 0.01). After adjustment for differences in age, gender, and Charnley class, a higher body mass index (greater obesity) was associated with lower activity (p = 0.05). With regard to the rate of polyethylene wear, decreased ambulatory activity may counterbalance increased weight, which could, at least in part, explain why weight has not had a consistent effect on polyethylene wear in clinical studies. Wear is a function of use, not time. The effect of obesity on activity should be considered in radiographic studies of wear and other outcome assessments of total joint replacements.
Microstructural properties of the distal growth plate of the rabbit radius and ulna: Biomechanical, biochemical, and morphological studies
Authors: Fujii Toshiyuki , Takai Shinro , Arai Yoshiyuki , Kim Wookcheol , Amiel David , Hirasawa Yasusuke 
Published: February 2005

AbstractThe purposes of this study were to define the tensile properties of each zone of the rabbit growth plate and to correlate them with the microarchitecture and biochemical composition of the zones. The epiphysis‐growth plate‐metaphysis complex was obtained from the radius and ulna of 20 8‐week‐old rabbits. Four dye markers were placed on the growth plate. The complex was loaded to failure with a tensile testing machine, and the strain behavior was recorded simultaneously with a microscope, a charge‐coupled device camera, and a video dimension‐analyzer system. The collagenous fiber architecture of each zone was examined with a microscope, and the collagen content of each zone was also determined. The tangent modulus of the resting zone was 75% stiffer than that of the other two zones. The highest values for strain at failure and energy absorbed to failure were observed in the hypertrophic zone, and the total collagen content was highest in the proliferating zone. The collagen fibers were more randomly aligned in the resting zone than in the other two zones. The diversity observed in the microarchitecture of the rabbit growth plate correlates with the zone‐dependent differences in its mechanical properties.
Efficiency of systematic sampling in histomorphometric bone research illustrated by hydroxyapatite‐coated implants: Optimizing the stereological vertical‐section design
Authors: Overgaard SøRen , Søballe Kjeld , Gundersen Hans Jørgen G. 
Published: February 2005

AbstractThe sampling efficiency of the unbiased stereological vertical‐section method was analyzed in five hydroxyapatite‐coated implants. They were inserted into humans and harvested after 1 year. To find an optimal sampling design for histomorphometric analyses, sampling efficiency was estimated by variance analyses at different sampling levels (humans, sections, fields of view, and number of counting items) and intensities. Only minor changes in variance were observed when the initial scheme was reduced to include just one of the two possible implant sides, every third field of view, and half the density of the probe; this reduced the total workload at the microscope to less than 10% for all sections. In addition, the number of sections for analysis could be reduced to every fourth section per implant (three to four sections for evaluation) without significantly increasing variance. The study demonstrated that biological variation contributed to the majority of the total observed variance. Optimizing the sampling design could significantly reduce the workload at the hard‐tissue microtome and the microscope without reducing the quality of the data that were unbiased and that had low sampling variance as compared with the true biological variation.
Vertebral trabecular bone microscopic tissue elastic modulus and hardness do not change in ovariectomized rats
Authors: Guo X. Edward , Goldstein Steven A. 
Published: February 2005

AbstractOvariectomized rats have been used extensively and have received substantial acceptance as animal models for postmenopausal osteoporosis. However, little is known about the microscopic tissue properties of rat vertebral bone, especially during osteoporosis caused by estrogen depletion. This study applied a new nanoindentation technique to quantify the microscopic mechanical properties of vertebral trabecular bone tissue in ovariectomized rats. Seventeen‐week‐old Sprague‐Dawley rats underwent an ovariectomy. After death at 37 weeks, the fraction of the trabecular bone area of the lumbar vertebrae (L4) was measured with scanning electron microscopy and the elastic modulus and hardness were determined with the nanoindentation technique. The bone area fraction was reduced significantly after the ovariectomy. However, the elastic modulus and hardness did not change significantly at the microscopic level. The results indicate that estrogen‐dependent osteoporosis in rats manifests in a loss of bone mass whereas the elastic and hardness properties of the surviving bone tissue remain relatively unchanged.
Amelioration of disease severity by intraarticular hylan therapy in bilateral canine osteoarthritis
Authors: Marshall K. W. , Manolopoulos V. , Mancer K. , Staples J. , Damyanovich A. 
Published: February 2005

AbstractBecause of its high molecular weight, the glycosaminoglycan molecule hyaluronan is responsible for the viscoelastic properties of normal synovial fluid. In osteoarthritis, the concentration and molecular weight of hyaluronan in synovial fluid is diminished; this impairs the ability of synovial fluid to effectively lubricate joints, absorb loads, and exert anti‐inflammatory effects. Using a bilateral anterior cruciateligament transection and partial neurectomy canine model of osteoarthritis, this study examined the effect of viscosupplementation with hylan G‐F 20 as a treatment for osteoarthritis, this study examined the effect of viscosupplementation with hylan G‐F 20 as a treatment for osteoarthritis. Twelve dogs underwent bilateral arthroscopic anterior cruciate‐ligament transections and partial neurectomy of the knee joints. Beginning 1 week after the operation, six dogs received three weekly 500‐μl injections of hylan G‐F 20 in one knee and a sham injection of saline solution in the contralateral knee (early‐treatment group). The remaining six animals underwent the same treatment 2 months following the procedure (late‐treatment group). All dogs were killed at 8 months, and both knees were evaluated for gross pathology, histology, and proteoglycan content. In addition, with use of 500‐MHz [1H] magnetic resonance spectroscopy, the synovial fluid from both knees was assessed for changes in metabolic profile. Differences in outcome were analyzed with pairedttests. Gross pathological and histological examination revealed significantly less severe changes of osteoarthritis in knees treated with hylan G‐F 20 2 months after surgery than in the contralateral untreated knees. Magnetic resonance spectroscopy of the specimens in this late‐treatment group showed significantly decreased glucose concentrations and significantly elevated isoleucine levels in the synovial fluid from knees treated with hylan G‐F 20 compared with the controls. Previous magnetic resonance spectroscopy had shown that glucose concentrations increase with the onset of osteoarthritis and eventually diminish in end‐stage osteoarthritis. The three injections of hylan were given after osteoarthritis was established, and the severity of the disease was ameliorated in the treated knees 6 months after treatment. This occurred although hylan G‐F 20 is almost certainly cleared from joints by lymphatics within 4 weeks of injection, suggesting that hylan therapy can retard the progression of osteoarthritis for periods of time extending beyond the intraarticular residence time of the injected molecules and that hylan injections given at relatively early stages of osteoarthritis may have a chondroprotective effect. No changes in outcome were noted in the animals that received hylan G‐F 20 immediately following surgery.
Pregnancy affects cellular activity, but not tissue mechanical properties, in the healing rabbit medial collateral ligament
Authors: Hart David A. , Reno Carol , Frank Cyril B. , Shrive Nigel G. 
Published: February 2005

AbstractRecently, evidence has been accumulating that ligament and joint laxity is altered in women and rabbits during pregnancy. Furthermore, many female adolescents injure ligaments through participation in athletics and other activities. Therefore, to determine whether pregnancy has different effects on the injured and uninjured medial collateral ligament of the rabbit knee, we investigated cellular changes (mRNA levels) and alterations in tissue properties (biomechanics) accompanying pregnancy in animals with the medial collateral ligament injured during adolescence and bred for their primigravid pregnancy as young adults. Assessment of mRNA levels for matrix molecules, matrix metalloproteinases and tissue inhibitor of metalloproteinase‐1, growth factors and sex hormone receptors, inflammatory cytokines, inducible nitric oxide synthase, and cyclooxygenase‐2 by semiquantitative reverse transcription‐polymerase chain reaction revealed that pregnancy had different impacts on scar and uninjured tissue for six of 15 genes assessed. A pregnancy‐associated increase in laxity of the medial collateral ligament was observed for rabbits in the uninjured primigravida group; however, no increase was observed for injured rabbits during pregnancy. The injured ligament was already significantly more lax than the normal counterpart, and pregnancy did not lead to additional laxity or prevent the normal decline in laxity as the scar matured in nonpregnant animals. These results indicate that the impact of pregnancy on laxity and cell activity of the medial collateral ligament is dependent on whether the ligament is uninjured or injured. Pregnancy had no significant effect on structural (stiffness and failure load), material (stress at failure and Young's modulus), or viscoelastic (cyclic and static relaxation) properties of tissue from uninjured or injured medial collateral ligament. Therefore, the properties of the healing ligament were not adversely affected during pregnancy in this experimental model. However, it remains to be determined if these results with an injured medial collateral ligament can be extrapolated to the injured anterior cruciate ligament.
Compressive compared with tensile loading of medial collateral ligament scar in vitro uniquely influences mRNA levels for aggrecan, collagen type II, and collagenase
Authors: Majima Tokifumi , Marchuk Linda L. , Sciore Paul , Shrive Nigel G. , Frank Cyril B. , Hart David A. 
Published: February 2005

AbstractTo test the hypothesis that loading conditions can be used to engineer early ligament scar behaviors, we used an in vitro system to examine the effect that cyclic hydrostatic compression and cyclic tension applied to 6‐week rabbit medial collateral ligament scars had on mRNA levels for matrix molecules, collagenase, and the proto‐oncogenes c‐fos and c‐jun. Our specific hypothesis was that tensile stress would promote more normal mRNA expression in ligament whereas compression would lead to higher levels of mRNA for cartilage‐like molecules. Femur (injured medial collateral ligament)‐tibia complexes were subjected to a hydrostatic pressure of 1 MPa or a tensile stress of 1 MPa of 0.5 Hz for 1 minute followed by 14 minutes of rest. On the basis of a preliminary optimization experiment, this 15‐minute testing cycle was repeated for 4 hours. Semiquantitative reverse transcription‐polymerase chain reaction analysis was performed for mechanically treated medial collateral ligament scars with use of rabbit specific primer sets for types I, II, and III collagen, decorin, biglycan, fibromodulin, versican, aggrecan, collagenase, c‐fos, c‐jun, and a housekeeping gene, glyceraldehyde‐3‐phosphate dehydrogenase. Cyclic hydrostatic compression resulted in a statistically significant increase in mRNA levels of type‐II collagen (171% of nonloaded values) and aggrecan (313% of nonloaded values) but statistically significant decreases in collagenase mRNA levels (35% of nonloaded values). Cyclic tension also resulted in a statistically significant decrease in collagenase mRNA levels (66% of nonloaded values) and an increase in aggrecan mRNA levels (458% of nonloaded values) but no significant change in the mRNA levels for the other molecules. The results show that it is possible to alter mRNA levels for a subset of genes in scar tissue by supplying unique mechanical stimuli in vitro and thus that further investigation of scar engineering for potential reimplantation appears feasible.
Morphometric analysis of canine skeletal muscles following experimental callus distraction according to the ilizarov method
Authors: Fink Bernd , Neuen‐Jacob Eva , Madej Marius , Lienert Arnd , Rüther Wolfgang 
Published: February 2005

AbstractMuscle fiber diameter and fiber‐type distribution were analyzed during callus distraction. The right tibia in 24 beagles was lengthened 2.5 cm by callus distraction after osteotomy and application of a ring fixator. Distraction was started at the fifth postoperative day, at a rate of two times for 0.5 mm per day. Twelve dogs that underwent limb‐lengthening and three dogs in the control group that did not undergo limb‐lengthening were killed at the end of the 25‐day distraction phase (group A). The remaining dogs (12 that underwent limb‐lengthening and three that did not) were killed after an additional consolidation period of 25 days (group B). The tibialis anterior, extensor digitorum longus, peroneus longus, and gastrocnemius muscles were removed from the right limb (which had undergone distraction) and the left control side of each animal. Crosscut cryostat sections were stained by adenosine triphosphatase at pH 4.3 and 9.4 to determine the size and distribution of types I and II fibers. Morphometric analysis of the muscle fibers was performed by a computer‐assisted two‐point technique. On the lengthened side, the muscles revealed marked atrophy affecting predominantly type‐II fiber in the dogs in group A and affecting both fiber types in dogs in group B. Fiber density increased in both groups. In addition, fiber‐type grouping indicative of reinnervation was obvious in group B. Fiber‐type distribution in the dogs in group B showed a shift toward type I in the tibialis anterior (p = 0.043) and extensor digitorum longus (p = 0.034) muscles and a shift toward type II in the gastrocnemius (p = 0.038). The data show that tension‐stress during tibial lengthening leads to atrophy of type‐II fiber, reflecting disuse of muscle fiber in the distraction period as well as neurogenic atrophy followed by the reinnervation processes. Furthermore, the data are consistent with the occurrence of histoneogenesis during limb‐lengthening resulting in an increase in fiber density.
Primary resective shortening followed by distraction osteogenesis for limb reconstruction: A comparison with simple lengthening
Authors: Meffert Rainer H. , Tis John E. , Inoue Nozomu , McCarthy Edward F. , Brug Erwin , Chao Edmund Y. S. 
Published: February 2005

AbstractResective distraction osteogenesis is a new approach to treat segmental diaphyseal bone defects by primary limb shortening and secondary distraction osteogenesis from the same site. A rabbit model was introduced to compare the bone‐regeneration characteristics of this technique with those of simple lengthening procedures. Twenty‐four skeletally mature New Zealand White rabbits were divided into two equal groups. In the test group, limbs were lengthened after a 10‐mm segmental diaphyseal bone resection and limb shortening. In the control group, a simple subperiosteal osteotomy for limb lengthening was performed without resection. New bone formation was evaluated mechanically, radiologically, histomorphometrically, and densitometrically. Bone bridging occurred in all animals. Normalized mechanical values for the newly reconstructed tibiae demonstrated similar torsional stiffness (71 ± 3.3 compared with 71 ± 8.2%; p = 0.95) and strength (64 ± 5.3 compared with 68 ± 7.3%; p = 0.66) in the two groups. The average normalized callus diameter was significantly greater in the test group than in the control group (p < 0.01). The remodeling index calculated from densitometry, however, showed a significantly less progressed stage of remodeling in the test group (p < 0.05). Histomorphometric analysis of the callus center supported this finding, showing significantly lower values for trabecular thickness (p < 0.05) and total bone volume (p < 0.01) in the test group. The results demonstrated the possibility of new bone formation after resection and monofocal shortening. This suggests a new therapeutic option to treat diaphyseal segmental bone defects.
Hyaluronan‐based polymers in the treatment of osteochondral defects
Authors: Solchaga Luis A. , Yoo Jung U. , Lundberg Magnus , Dennis James E. , Huibregtse Barbara A. , Goldberg Victor M. , Caplan Arnold I. 
Published: February 2005

AbstractArticular cartilage in adults has limited ability for self‐repair. Some methods devised to augment the natural healing response stimulate some regeneration, but the repair is often incomplete and lacks durability. Hyaluronan‐based polymers were tested for their ability to enhance the natural healing response. It is hypothesized that hyaluronan‐based polymers recreate an embryonic‐like milieu where host progenitor cells can regenerate the damaged articular surface and underlying bone. Osteochondral defects were made on the femoral condyles of 4‐month‐old rabbits and were left empty or filled with hyaluronan‐based polymers. The polymers tested were ACP sponge, made of crosslinked hyaluronan, and HYAFF‐11 sponge, made of benzylated hyaluronan. The rabbits were killed 4 and 12 weeks after surgery, and the condyles were processed for histology. All 12‐week defects were scored with a 29‐point scale, and the scores were compared with a Kruskall‐Wallis analysis of variance on ranks. Untreated defects filled with bone tissue up to or beyond the tidemark, and the noncalcified surface layer varied from fibrous to hyaline‐like tissue. Four weeks after surgery, defects treated with ACP exhibited bone filling to the level of the tidemark and the surface layer was composed of hyaline‐like cartilage well integrated with the adjacent cartilage. At 12 weeks, the specimens had bone beyond the tidemark that was covered with a thin layer of hyaline cartilage. Four weeks after surgery, defects treated with HYAFF‐11 contained a rim of chondrogenic cells at the interface of the implant and the host tissue. In general, the 12‐week defects exhibited good bone fill and the surface was mainly hyaline cartilage. Treated defects received significantly higher scores than untreated defects (p < 0.05), and ACP‐treated defects scored significantly higher than HYAFF‐11‐treated defects (p < 0.05). The introduction of these hyaluronan‐based polymers into defects provides an appropriate scaffolding and favorable microen‐vironment for the reparative process. Further work is required to fully assess the long‐term outcome of defects treated with these polymers.
Healing of canine articular cartilage defects treated with microfracture, a type‐II collagen matrix, or cultured autologous chondrocytes
Authors: Breinan Howard A. , Martin Scott D. , Hsu Hu‐Ping , Spector Myron 
Published: February 2005

AbstractThe effects of three different treatments on the healing of articular cartilage defects were compared with use of a previously developed canine model. In the articular surface of the trochlear grooves of 12 adult mongrel dogs, two 4‐mm‐diameter defects were made to the depth of the tidemark. Four dogs were assigned to each treatment group: (a) microfracture treatment, (b) microfracture with a type‐II collagen matrix placed in the defect, and (c) type‐II matrix seeded with cultured autologous chondrocytes. After 15 weeks, the defects were studied histologically. Data quantified on histological cross sections included areal or linear percentages of specific tissue types filling the defect, integration of reparative tissue with the calcified and the adjacent cartilage, and integrity of the subchondral plate. Total defect filling (i.e., the percentage of the cross‐sectional area of the original defect filled with any type of reparative tissue) averaged 56–86%, with the greatest amount found in the dogs in the microfracture group implanted with a type‐II collagen matrix. The profiles of tissue types for the dogs in each treatment group were similar: the tissue filling the defect was predominantly fibrocartilage, with the balance being fibrous tissue. There were no significant differences in the percentages of the various tissue types among dogs in the three groups.