ISSN:0736-0266    

DOI:10.1002/jor.1100170402

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1999

数据来源: WILEY

摘要:

AbstractThe addition of insulin‐like growth factor‐I to cartilage cultures is known to stimulate the synthesis of proteoglycan and type‐II collagen in explant and monolayer studies. The purpose of this study was to determine the effects of long‐term supplementation with insulin‐like growth factor‐I in chondrocytes cultured in fibrin discs as a preliminary investigation toin vivoapplication of chondrocyte/insulin‐like growth factor‐I/fibrin grafts to articular‐cartilage repair procedures. Chondrocyte‐fibrin cultures were maintained for 14 days, with insulin‐like growth factor‐I added at varying concentrations of 0, 10, 50, or 100 ng/ml medium. Cultures supplemented with 50 or 100 ng of growth factor/ml had increased levels of aggrecan and type‐IIB procollagen mRNA, and translation to aggrecan and type‐IIB collagen was confirmed by dye‐binding assay of total proteoglycan, type‐II collagen immunohistochemistry, and determination of collagen content by highperformance liquid chromatography. Maintenance of the chondrocyte phenotype during the 14 days of culture was confirmed by round cell morphology on routine staining, expression of type‐II procollagen mRNA onin situhybridization, evidence of production of pericellular type‐II collagen on immunocytochemistry, synthesis of large‐molecular‐size aggrecan monomer on CL‐2B column chromatography, and lack of appreciable message expression for type I or IIA collagen on Northern blot hybridization. Dose‐response effects of insulin‐like growth factor‐I on the expression of chondrocyte matrix constituents were most pronounced at 50 and 100 ng of growth factor per milliliter of medium. These data confirm that (a) culture of chondrocytes for extended periods in three‐dimensional cultures of fibrin maintains the chondrocyte phenotype and (b) supplementation with increasing concentrations of insulin‐like growth factor‐I enhances chondrocyte matrix synthesis and may provide a means to enhance chondrocyte phenotypic stability an

ISSN:0736-0266    

DOI:10.1002/jor.1100170403

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1999

数据来源: WILEY

摘要:

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 con

ISSN:0736-0266    

DOI:10.1002/jor.1100170404

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1999

数据来源: WILEY

摘要:

AbstractWe evaluated the effect of low intensity‐pulsed ultrasound stimulation on rat chondrocytes in vitro using two different 1.0‐MHZultrasound 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). Thein vitroresults 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 fr

ISSN:0736-0266    

DOI:10.1002/jor.1100170405

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1999

数据来源: WILEY

摘要:

AbstractConflicting data have been reported on the spatial distribution of type X‐collagen expression in osteoarthritis, and no concise data exist on a possible correlation between type X‐collagen expression and clinical and radiological alterations. Well defined clinical and radiological data were compared with histopathological and immunohistochemical findings to investigate the expression of type‐X collagen in osteoarthritis of the hip joint. Femoral heads were obtainedin totofrom 11 patients undergoing routine hip arthroplasty for femoral neck fractures (n = 3) or osteoarthritis (n = 8) and from 13 patients (age: 12 days to 69 years) without any evidence of hip‐joint pathology. Whole coronal sections from the femoral head were decalcified for routine histology and immunohistochemical analysis with use of type‐specific monoclonal antibodies to type‐X collagen. Our results demonstrate that type‐X collagen is consistently found in osteoarthritic cartilage and is absent from normal adult cartilage (including the region of calcified cartilage). Except for the occurrence of type‐X collagen in the middle zone of articular cartilage in advanced stages of osteoarthritis, there is no specific change in the staining pattern or intensity for the collagen during osteoarthritis, particularly when the staining is related to clinical and radiological parameters. Hardly more than 20% of the extracellular matrix stained for type‐X collagen; therefore, we suggest that, in most cases, this type of collagen may not play a direct biomechanical role in the weakening of osteoarthritic cartilage but rather may contribute indirectly to a disturbance of the disc biomechanics by altering matrix‐molecule interaction. However, expression of type‐X collagen may indicate a change in chondrocyte phenotype that consistently coincides with the formation of chondrocyte clusters, one of the first alterations in osteoarthritis visible on h

ISSN:0736-0266    

DOI:10.1002/jor.1100170406

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1999

数据来源: WILEY

摘要:

AbstractLoss of or damage to the meniscus alters the pattern of loading in the knee joint and frequently leads to cartilage degeneration and osteoarthritis. The mechanical properties of articular cartilage have been shown to reflect the extent of cartilage degeneration in human osteoarthritis and in experimental models of joint disease, but there is little experimental data documenting changes in cartilage mechanics following meniscectomy. We hypothesized that the tensile properties of the surface zone of articular cartilage are altered following total medial meniscectomy. Twelve mongrel dogs underwent complete resection of the medial meniscus in the right knee, and the femoral cartilage was studied 12 weeks after the operation. We performed uniaxial, tensile stress‐relaxation tests to determine the equilibrium tensile modulus of surface‐zone cartilage. Water and glycosaminoglycan content were also measured at site‐matched locations. The tensile moduli of the cartilage decreased significantly following meniscectomy. The linear region modulus decreased by 40%, from 25.5 ± 7.7 to 15.3 ± 7.2 MPa. There was a weak (r = −0.45), but significant, correlation between the linear region modulus and the gross morphological grade for cartilage damage. Water and glycosaminoglycan content did not change following meniscectomy. Composition was not correlated with mechanical properties or morphological grade, suggesting that cartilage structure may play a more important role than composition in determining the mechanical properties. The observed decrease in cartilage material properties provides a quantitative measure of the loss of cartilage function following meniscectomy and reflects a pattern of change that is consistent with damage to the collagen‐proteoglycan so

ISSN:0736-0266    

DOI:10.1002/jor.1100170407

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1999

数据来源: WILEY

摘要:

AbstractThe development of normal joints depends on mechanical functionin utero. Experimental studies have shown that the normal surface topography of diarthrodial joints fails to form in paralyzed embryos. We implemented a mathematical model for joint morphogenesis that explores the hypothesis that the stress distribution created in a functional joint may modulate the growth of the cartilage anlagen and lead to the development of congruent articular surfaces. We simulated the morphogenesis of a human finger joint (proximal interphalangeal joint) between days 55 and 70 of fetal life. A baseline biological growth rate was defined to account for the intrinsic biological influences on the growth of the articulating ends of the anlagen. We assumed this rate to be proportional to the chondrocyte density in the growing tissue. Cyclic hydrostatic stress caused by joint motion was assumed to modulate the baseline biological growth, with compression slowing it and tension accelerating it. Changes in the overall shape of the joint resulted from spatial differences in growth rates throughout the developing chondroepiphyses. When only baseline biological growth was included, the two epiphyses increased in size but retained convex incongruent joint surfaces. The inclusion of mechanobiological‐based growth modulation in the chondroepiphyses led to one convex joint surface, which articulated with a locally concave surface. The articular surfaces became more congruent, and the anlagen exhibited an asymmetric sagittal profile similar to that observed in adult phalangeal bones. These results are consistent with the hypothesis that mechanobiological influences associated with normal function play an important role in the regulation of joint morphogenesi

ISSN:0736-0266    

DOI:10.1002/jor.1100170408

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1999

数据来源: WILEY

摘要:

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

ISSN:0736-0266    

DOI:10.1002/jor.1100170409

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1999

数据来源: WILEY

摘要:

AbstractClinical and experimental evidence suggest that periprosthetic bone loss following total hip arthroplasty is caused in part by stress‐shielding. Changes in bone stress in the proximal femur following implantation can be estimated with use of composite beam theory. We hypothesized that the degree of stress‐shielding predicted by beam theory correlates with the magnitude of bone loss following cemented total hip arthroplasty. We analyzed cross sections from the proximal femur of 13 patients who had undergone unilateral cemented total hip arthroplasty. A matching implant was inserted contralaterally, and the cross‐sectional properties of the implant and bone and the bone density were determined. Bone loss was calculated on the basis of differences between contralateral (control) and ipsilateral (remodeled) sections and correlated to several beam‐theory parameters calculated from the control sections: implant rigidity, bone rigidity, ratio of implant to bone rigidity, and predicted decrease in bone stress. All parameters except implant rigidity were significantly correlated with bone loss (p<0.05). Parameters that included implant and bone properties were more strongly correlated with bone loss than were those based on bone properties alone. The predicted decrease in bone stress explained 50‐60% of the variance in bone loss. The data also indicated that patients were not likely to lose substantial amounts of bone unless the reduction in bone stress exceeded a threshold value. Although limited by a small and heterogeneous sample, these results indicate that beam‐theory predictions correlate with the degree of femoral resorption and should be investigated further as a means to identify patients at high risk fo

ISSN:0736-0266    

DOI:10.1002/jor.1100170410

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1999

数据来源: WILEY

摘要:

AbstractThe objective of this study was to provide quantitative data on hip‐joint incongruity and pressure during a simulated walking cycle and on articular‐cartilage thickness in the same set of specimens. Using a casting technique in eigth specimens of the human hip (age: 18‐75 years), we determined the width of the joint space (incongruity) required at minimal load for contact at four phases of the gait cycle. The pressure distribution, measured with pressure‐sensitive film, was determined at physiologic load magnituded on the basis ofin vivomeasurements of hip‐joint forces. Cartilage thickness was assessed with A‐mode ultrasound. At minimal loading, the average maximum width of the joint space ranged from 1.1 to 1.5 mm in the acetabular roof, with the contact areas located ventro‐superiorly and dorso‐inferiorly throughout the gait cycle. At physiological loading, the width decreased and the contact areas covered the complete articular surface during midstance and heel‐off but not during heel‐strike or toe‐off. The pressure distribution was inhomogeneous during all phases, with average maximum pressures of 7.7 ± 1.95 MPa at midstance. The cartilage thickness varied considerably throughout the joint surfaces; maxima greater than 3 mm were found ventro‐superiorly. These data can be used to generate and validate computer models to determine the loadsharing between the interstitial fluid and the solid proteoglycan‐collagen matrix of articular cartilage, the latter being relevant for the initiation of mechanically indu

ISSN:0736-0266    

DOI:10.1002/jor.1100170411

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1999

数据来源: WILEY