bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bone marrow cells produce soluble factors that inhibit osteoclast activity
Authors: Ninomiya James T. , Bi Yanming , Banks Michael A. , Lavish Sandra A. , Goldberg Victor M. , Greenfield Edward M. 
Published: February 2005

AbstractCytokines that stimulate bone resorption are produced by cells found in bone marrow. However, marrow cells produce multiple factors, some of which may be inhibitors of osteoclast differentiation or activity. Thus, it is not possible to predict a priori whether the mixture of factors produced by marrow cells will have a net stimulatory or inhibitory effect on bone resorption. In this study, we showed that the net effect of whole marrow is to inhibit osteoclast activity induced by parathyroid hormone. Fractionation of the marrow revealed that the inhibitory activity was in the marrow fluid. However, conditioned media obtained from marrow cell cultures also inhibited osteoclast activity. Thus, it is likely that the inhibitory factors are produced in vivo by cells residing in the marrow. These inhibitory factors may represent a physiological regulatory process that plays an important role in maintaining the balance between bone resorption and formation. Because we have previously shown that interleukin‐6 is one of the cytokines that parathyroid hormone induces in osteoblastic cells to stimulate osteoclast activity, one potential mechanism by which the marrow‐derived inhibitory factors might act is by preventing this production of interleukin‐6. However, we found that the marrow cell‐conditioned media do not inhibit the production or activity of interleukin‐6. Thus, the inhibitory factors appear to block osteoclast activity through a mechanism that does not involve interleukin‐6. Taken together, these results demonstrate the importance of factors that inhibit bone resorption and emphasize that the presence of cytokines that stimulate bone resorption in conditions such as osteoporosis and orthopaedic implant loosening should be interpreted with caution unless evidence exists demonstrating their functional importance.
Intermittent pneumatic compression of legs increases microcirculation in distant skeletal muscle
Authors: Liu Kang , Chen Long‐En , Seaber Anthony V. , Johnson Glenn W. , Urbaniak James R. 
Published: February 2005

AbstractIntermittent pneumatic compression has been established as a method of clinically preventing deep vein thrombosis, but the mechanism has not been documented. This study observed the effects of intermittent pneumatic compression of legs on the microcirculation of distant skeletal muscle. The cremaster muscles of 80 male rats were exposed, a specially designed intermittent pneumatic‐compression device was applied to both legs for 60 minutes, and the microcirculation of the muscles was assessed by measurement of the vessel diameter in three categories (10–20, 21–40, and 41–70 μm) for 120 minutes. The results showed significant vasodilation in arterial and venous vessels during the application of intermittent pneumatic compression, which disappeared after termination of the compression. The vasodilation reached a maximum 30 minutes after initiation of the compression and could be completely blocked by an inhibitor of nitric oxide synthase, NG‐monomethyl‐L‐arginine (10 μmol/min). A 120‐minute infusion of NG‐monomethyl‐L‐arginine, beginning coincident with 60 minutes of intermittent pneumatic compression, resulted in a significant decrease in arterial diameter that remained at almost the same level after termination of the compression. The magnitude of the decrease in diameter in the group treated with intermittent pneumatic compression and NG‐monomethyl‐L‐arginine was comparable with that in the group treated with NG‐monomethyl‐L‐arginine alone. The results imply that the production of nitric oxide is involved in the positive influence of intermittent pneumatic compression on circulation. It is postulated that the rapid increase in venous velocity induced by intermittent pneumatic compression produces strong shear stress on the vascular endothelium, which stimulates an increased release of nitric oxide and thereby causes systemic vasodilation.
Effect of seeding duration on the strength of chondrocyte adhesion to articular cartilage
Authors: Schinagl Robert M. , Kurtis Melissa S. , Ellis Kristi D. , Chien Shu , Sah Robert L. 
Published: February 2005

AbstractChondrocyte adhesion to cartilage may play an important role in the repair of articular defects by maintaining cells in positions where their biosynthetic products can contribute to the repair process. The objective of this in vitro study was to determine the effect of the duration of seeding time on the ability of chondrocytes to resist detachment from cartilage when subjected to mechanical perturbation (fluid‐induced shear stress). Suspensions of adult bovine articular chondrocytes were prepared from primary, high‐density monolayer cultures and infused into a parallel‐plate shear‐flow chamber where they settled onto 50‐μm‐thick sections of bovine articular cartilage at a density of approximately 20,000 cells/cm2. The chondrocytes were seeded and allowed to attach to the cartilage surface for specific durations (5‐40 minutes) in medium including 10% serum at 22°C, after which the cells were exposed to fluid flow‐induced shear stresses (6‐90 Pa). The fraction of detached cells at each shear stress was calculated from microscopic images. Shear stress was applied for 1 minute because this lenght of time was sufficient to induce steady‐state cell detachment. Increasing the duration of cell seeding led to a more firm attachment of chondrocytes to cartilage. After 9 minutes of seeding, 50% cell detachment was induced by gravitational force alone. After 40 minutes of seeding, 50% detachment required 26 Pa of shear stress. Extrapolation of the data to account for the effect of repeated applications of cell suspensions to an individual cartilage substrate indicated that for a freshly prepared cartilage section, 50% detachment was induced by gravity after 25 minutes of seeding and by 2.3 Pa of shear stress after 40 minutes of seeding. The increase in resistance to shear stress‐induced cell detachment with increasing seeding duration suggests that it may be beneficial to allow chondrocytes to stabilize in the absence of applied load for some time after chondrocyte transplantation for cartilage repair in vivo.
Callus formation and fixation rigidity: A fracture model in rats
Authors: Probst A. , Jansen H. , Ladas A. , Spiegel H. U. 
Published: February 2005

AbstractTo produce different amounts of callus in rats. we devised a procedure to fix leg fractures using intramedullary nails that differ in bending rigidity. We inserted a silicone cannula into the intact diaphysis of the tibia of rats that had already been killed and then fractured the tibia by a three‐point bending technique. The fracture was stabilised by insertion of either a stainless‐steel or polypropylene nail into the silicone cannula. Biomechanical testing showed that the initial stiffness of the fractures differed between the two nail types by a factor of 16. In vivo, 16 Wistar rats were operated on by the same technique to study the formation of callus. Four weeks after fracture, the size of the callus differed significantly between the steel‐nailed and polypropylene‐nailed fractures. In conclusion, mechanically differing internal fixation devices led to different callus responses in rats when all other factors were kept equal.
Effect of serum proteins on osteoblast adhesion to surface‐modified bioactive glass and hydroxyapatite
Authors: El‐Ghannam A. , Ducheyne P. , Shapiro I. M. 
Published: February 2005

AbstractPrevious studies indicate that modification of the surface of porous bioactive glass promotes osteoblast function. We hypothesize that bone formation on treated bioactive glass is due to the selective adsorption of serum attachment proteins. To test this hypothesis, we examined the profile of proteins adsorbed to treated bioactive glass and compared these proteins with those adsorbed to untreated bioactive glass and porous hydroxyapatite. Porous bioactive glass was treated with Tris‐buffered electrolyte solution to generate a calcium phosphate‐rich surface layer and then immersed in tissue‐culture medium containing 10% serum. Proteins adsorbed to the ceramic surfaces were analyzed by sodium dodecyl sulfate‐polyacrylamide gel electrophoresis and Western blot analysis. Porous hydroxyapatite bound a higher amount of total protein than did the other substrates. However, surface‐modified porous bioactive glass adsorbed more fibronectin than did hydroxyapatite. The effect of serum‐protein adsorption on osteoblast adhesion to bioactive glass and hydroxypatite was also evaluated. Cell adhesion to porous bioactive glass that was either surface‐modified and serum‐treated was significantly greater than to porous bioactive glass that was either surface‐modified or serum‐treated. Furthermore, cell adhesion to porous bioactive glass treated to form the dual layer of calcium phosphate and serum protein was significantly higher than adhesion to porous hydroxyapatite with adsorbed serum protein. Results of the study strongly suggest that adsorption of serum fibronectin to the surface of modified porous bioactive glass coated with calcium phosphate may be responsible for enhanced osteoblast adhesion.
Experimental acute hematogenous osteomyelitis in mice. II. Influence of Staphylococcus aureus infection on T‐cell immunity
Authors: Yoon K. S. , Fitzgerald R. H. , Sud S. , Song Z. , Wooley P. H. 
Published: February 2005

AbstractA murine model of acute hematogenous osteomyelitis was used to study the immune response following Staphylococcus aureus infection and to examine the hypothesis that the bacteria may modify T‐cell responses due to the production of bacterial enterotoxins with mitogenic or superantigenic activity. Lymphnode T cell‐receptor expression was assessed with use of flow cytometry and reverse transcription‐polymerase chain reaction techniques, and increased apoptosis (programmed cell death) in T‐cell subsets was monitored. The expression and levels of circulating cytokines and T‐cell cytokines within tissues surrounding the damaged area of the proximal tibia were also investigated. Analysis of T‐cell receptors in experimental osteomyelitis revealed two distinct patterns of T‐cell evolution during the disease. Certain T‐cell subsets (Vβ2, Vβ3, Vβ9, and Vβ10) were activated and expanded during the first 24 hours after infection; they reached maximum levels 6 days after infection, followed by a return to pre‐infection levels. In contrast, other T‐cell subsets (Vβ11, Vβ12, Vβ13, Vβ14, and Vβ16) contracted during the first 24 hours after infection, followed by expansion to a maximum level 9 days after infection. Activation and proliferation of T‐cell subsets (notably Vβ14 T cells) was followed by apoptosis, suggesting that staphylococcal bone infection caused superantigenic‐like effects on the mouse immune system. Analysis of cytokine responses in local tissue revealed that the T‐cell cytokines interleukin‐2 and interferon‐γ showed a late and relatively short activation pattern compared with the inflammatory cytokines interleukin‐1, interleukin‐6, and tumor necrosis factor‐α. The results suggest that Staphylococcus aureus bone infection may undermine the antibacterial immune response through downregulation of T‐cell immunity and immune‐cytokine production, which could increase the severity of the systemic infection and local osseous destruction that occur with acute hematogenous osteomyelitis.
Stiffness and muscle function with age and reduced muscle use
Authors: Brown Marybeth , Fisher Jonathan S. , Salsich Gretchen 
Published: February 2005

AbstractChanges in passive muscle stiffness with age and disuse were assessed in male Fischer‐344 and Brown Norway rats. Three groups of rats were studied: young (approximately 7 months old), old (approximately 33 months old), and old that had undergone 2 weeks of hindlimb unweighting, a model of reduced muscle use. Four hindlimb muscles were examined: the soleus (postural), plantaris (locomotor), extensor digitorum longus (nonpostural), and peroneus longus (nonpostural). Supramaximal stimuli elicited peak tetanic tensions throughout the available range of motion (amount of muscle elongation before the maximal attainable contractile or tetanic tension is obtained) for each muscle, permitting the creation of length‐tension curves. Passive tension (amount encountered at each millimeter of change in muscle length) was also recorded throughout the available range of motion and was unchanged with aging and unchanged or reduced with hindlimb unweighting; muscle stiffness remained unchanged under both conditions. Passive tension, however, accounted for a greater proportion of total tension with age and particularly with hindlimb unweighting. A significant loss in muscle range of motion, resulting in a leftward shift in the length‐tension curve, occurred with aging in only the plantaris. Hindlimb unweighting resulted in a marked loss in muscle range for all four muscles studied, suggesting that the remaining muscle force was constrained to a very small arc. Significant declines in muscle mass and peak contractile tension, associated with age and hindlimb unweighting, were observed for all four muscles.
Localization and expression of cartilage oligomeric matrix protein by human rheumatoid and osteoarthritic synovium and cartilage
Authors: Cesare Paul E. Di , Fang Carrie , Leslie Michael P. , Valle Craig J. Della , Gold Julie M. , Tulli Hermina , Perris Roberto , Carlson Cathy S. 
Published: February 2005

AbstractSynovium and cartilage from patients with osteoarthritis or rheumatoid arthritis were analyzed for expression of cartilage oligomeric matrix protein. Immunostaining of synovium with antiserum to cartilage oligomeric matrix protein demonstrated positive staining in both diseases. In osteoarthritis, there was positive staining within the synovial cells and immediately subjacent connective tissue, with less intense staining in the deeper connective tissue. In rheumatoid arthritis, there was less intense staining within the synovial cells and marked intense staining in the deeper connective tissue. In situ hybridization performed with an antisense digoxigenin‐labeled riboprobe to human cartilage oligomeric matrix protein confirmed the presence of cartilage oligomeric matrix protein mRNA in the cells of the synovial lining in both types of synovium. Quantitative polymerase chain reaction with a cartilage oligomeric matrix protein MIMIC demonstrated increased cartilage oligomeric matrix protein mRNA in rheumatoid cartilage and synovium as compared with osteoarthritic cartilage and synovium, respectively; mRNA levels in rheumatoid synovium were similar to those from osteoarthritic chondrocytes. As a result of the high expression of cartilage oligomeric matrix protein from rheumatoid synovium, inflammatory synovium should be considered as a potential tissue source of cartilage oligomeric matrix protein in any investigation of biological markers of cartilage metabolism. The upregulated expression of cartilage oligomeric matrix protein in inflammatory tissues suggests its in vivo regulation by cytokines.
Enhanced repair of extensive articular defects by insulin‐like growth factor‐I‐laden fibrin composites
Authors: Nixon Alan J. , Fortier Lisa A. , Williams Janice , Mohammed Hussni 
Published: February 2005

AbstractStem cells indigenous to the cancellous spaces of the bone bed in an acute injury provide an important source of pluripotent cells for cartilage repair. Insulin‐like growth factor‐I facilitates chondrogenesis of bone marrow‐derived stem cells in long‐term culture and may enhance chondrogenesis in healing cartilage lesionsin vivo. This study examined the impact of insulin‐like growth factor‐I, gradually released from fibrin clots polymerizedin situ, on the recruitable stem‐cell pool in a full‐thickness critical cartilage defect model. Twelve full‐thickness 15‐mm cartilage lesions in the femoropatellar articulations of six young mature horses were repaired by an injection of autogenous fibrin containing 25 μg of human recombinant insulin‐like growth factor‐I or, in control joints, fibrin without the growth factor. All horses were killed at 6 months, and cartilage repair tissue and surrounding cartilage were assessed by histology, histochemistry, types I and II collagen immunohistochemistry, types I and II collagenin situhybridization, and matrix biochemical determinations. White tissue filled grafted and control lesions, with the growth factor‐treated defects being more completely filled and securely attached to the subchondral bone. A moderately improved chondrocyte population, more columnar cellular organization, and better attachment to the underlying bone were evident on histological evaluation of growth factor‐treated defects. Type‐II procollagen mRNA was abundantly present in the deeper half of the treated sections compared with moderate message expression in control tissues. Immunolocalization of type‐II collagen showed a preponderance of the collagen in growth factor‐treated lesions, confirming translation of type‐II message to protein. Composite histologic healing scores for treated defects were significantly improved over those for control defects. DNA content in the cartilage defects was similar in treated and control joints. Matrix proteoglycan content was similar in treated and control defects and lower in the defects than in the intact surrounding and remote cartilage of the treated and control joints. The proportion of type‐II collagen significantly increased in growth factor‐treated tissues. Fibrin polymers laden with insulin‐like growth factor‐I improved the histologic appearance and the proportion of type‐II collagen in healing, full‐thickness cartilage lesions. However, none of the biochemical or morphologic features were consistent with those of normal articular cartilage.
Low‐intensity ultrasound stimulates proteoglycan synthesis in rat chondrocytes by increasing aggrecan gene expression
Authors: Parvizi Javad , Wu Chi‐Chuan , Lewallen David G. , Greenleaf James F. , Bolander Mark E. 
Published: February 2005

AbstractWe evaluated the effect of low intensity‐pulsed ultrasound stimulation on rat chondrocytes in vitro using two different 1.0‐MHZ ultrasound signals with spatial and temporal average intensities of 50 or 120 mW/cm2. The pulses had a duration of 200 microseconds and were repeated every millisecond, with corresponding average peak‐pressure amplitudes of 230 or 360 kPa, respectively. Cells were stimulated one, three, or five times for 10 minutes each day starting the third day after plating. One group of cells was exposed to sham ultrasound as a control. The cultures were evaluated for cell proliferation (by [3H]thymidine incorporation and DNA measurement), steady‐state mRNA levels of α1(I) and α1(II) procollagens and aggrecan (by Northern blotting), and proteoglycan synthesis (by [35S]sulfate incorporation). The results revealed that ultrasound causes increases in the level of aggrecan mRNA (p < 0.05) and in proteoglycan synthesis (p < 0.03) after three and five treatments. Expression of mRNA for α1(II) procollagen increased over time, but ultrasound had no stimulatory effect. Expression of mRNA for α1(I) procollagen was initially low and remained unchanged with time. Although cell proliferation increased with time in both groups, there was no statistically significant difference between the cultures treated with ultrasound and the controls (p = 0.1). The in vitro results support our previous in vivo findings that low‐intensity ultrasound stimulates aggrecan mRNA expression and proteoglycan synthesis by chondrocytes, which may explain the role of ultrasound in advancing endochondral ossification, increasing the mechanical strength of fractures, and facilitating fracture repair.
Mechanical modulation of growth for the correction of vertebral wedge deformities
Authors: Mente Peter L. , Aronsson David D. , Stokes Ian A. F. , Iatridis James C. 
Published: February 2005

AbstractThis study tested the following hypotheses: (a) a vertebral wedge deformity created by chronic static asymmetrical loading will be corrected by reversal of the load asymmetry; (b) a vertebral wedge deformity created by chronic static asymmetrical loading will remain if the load is simply removed; and (c) vertebral longitudinal growth rates, altered by chronic static loading, will return to normal after removal of the load. An external fixator was used to impose an angular deformity (Cobb angle of 30°) and an axial compression force (60% body weight) on the ninth caudal (apical) vertebra in two groups of 125‐week‐old Sprague Dawley rats. This asymmetrical loading was applied to all rats for 4 weeks to create an initial wedge deformity in the apical vertebra. The rats from group I (load reversal) then underwent 1 week of distraction loading followed by 4 weeks of asymmetrical compressive loading with the imposed 30° Cobb angle reversed. The rats from group II (load removal) had the apparatus removed and were followed for 5 weeks with no external loading. Weekly radiographs were obtained and serial fluorochrome labels were administered to follow vertebral wedging. After the initial 4‐week loading period, the combined average wedge deformity that developed in the apical vertebra of the animals in both groups was 10.7 ± 4.4°. The group that underwent load reversal showed significant correction of the deformity with the wedging of the apical vertebra decreasing to, on average, 0.1 ± 1.4° during the 4 weeks of load reversal. Wedging of the apical vertebra in the group that underwent load removal significantly decreased to 7.3 ± 3.9° during the first week after removal of the load, but no significant changes in wedging occurred after that week. This indicated a return to a normal growth pattern following the removal of the asymmetrically applied loading. The longitudinal growth rate of the apical vertebra also returned to normal following removal of the load. Vertebrae maintained under a load of 60% body weight grew at a rate that was 59.4 ± 17.0% lower than that of the control vertebrae, whereas after vertebrae were unloaded their growth averaged 102.4 ± 31.8%. These findings show that a vertebral wedge deformity can be corrected by reversing the load used to create it and that vertebral growth is not permanently affected by applied loading.