摘要:

AbstractA 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‐

ISSN:0736-0266    

DOI:10.1002/jor.1100160502

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

年代:1998

数据来源: WILEY

摘要:

AbstractThis study examined fetal chondrocyte proliferation and function following exposure to transforming growth factor‐β and insulin‐like growth factor‐I. Fetal equine articular chondrocytes of the early third‐trimester were isolated and cultured in monolayer conditions, then exposed to 0,1,5, or 10 ng/ml transforming growth factor‐β or 0,10,50, or 100 ng/ml insulin‐like growth factor‐I for 48 hours. Proliferative responses were assessed by cell counts and [3H]thymidine uptake into precipitable DNA. Differentiated chondrocyte metabolic activity was determined by sulfated glycosaminoglycan quantitation,35[SO4] incorporation into precipitable glycosaminoglycan, and proteoglycan molecular sizing by CL‐2B column chromatography. Morphological changes seen on phase‐contrast microscopy included a larger proportion of rounded cells in monolayer cultures supplemented with insulin‐like growth factor‐I and cytotoxic changes in cells treated with transforming growth factor‐β. Both insulin‐like growth factor‐I and transforming growth factor‐β resulted in significant elevations of [3H]thymidine uptake; however, cell numbers did not rise sufficiently over the 48‐hour culture period to reach significant levels. Maximum mitogenic responses were evident at 50 and 100 ng/ml insulin‐like growth factor‐I and 5 ng/ml transforming growth factor‐β. The production of proteoglycan was also enhanced (435%) by exposure to 50 ng/ml insulin‐like growth factor‐I, and an increased proportion of larger proteoglycan monomer species was evident in cultures treated with 50 and 100 ng/ml insulin‐like growth factor‐I. A similar dose‐response was also evident in cultures treated with transforming growth factor‐β (maximal 164%' increase with 5 ng/ml), although the presence of serum in the culture medium altered the pattern of enhanced proteoglycan synthesis to favor the lower concentration of 1 ng/ml (191%). Additionally larger proteoglycan molecules were synthesized in response to high concentrations of transforming growth factor‐β in serum‐free cultures. Significant biochemical changes resulted from the addition of transforming growth factor‐β to fetal chondrocyte cultures; however, monolayer cultures that were treated with transforming growth factor‐β and supplemented with serum began to develop cellular toxicity, including nuclear pyknosis and cytoplasmic fragmentation. Degenerative cellular changes were not evident in cultures treated with insulin‐like growth factor‐I, and significant differentiated metabolic activity resulted from the presence of insulin‐like growth factor‐I in the culture medium. These data suggest that the responses of fetal chondrocytes to insulin‐like growth factor‐I and transforming growth factor‐β were enhanced compared with the responses of chondrocytes derived from postnatal animals and that these metabolically active cells can be primed by endogen

ISSN:0736-0266    

DOI:10.1002/jor.1100160503

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

年代:1998

数据来源: WILEY

摘要:

AbstractTransplantation of chondrocytes by injection or within carrier matrices has shown promise for augmenting the repair of articular cartilage defects.In vivo, transplanted chondrocytes are exposed to mechanical forces. Thisin vitrostudy examined the effect of a step application of compressive load to chondrocytes after the cells had been seeded onto a cartilage surface. Bovine chondrocytes were transplanted onto bovine cartilage disks, allowed to attach for 1 hour or 4 days, and subjected to compression through overlying cartilage disks in a confined compression configuration. Before use, the disks were lyophilized to lyse the endogenous chondrocytes and thereby allow assessment of the metabolic activity of the transplanted cells. During a 16‐hour application of compressive stress of 0‐24‐0.72 MPa, proteoglycan synthesis, assessed as [35S]sulfate incorporation into macromolecules. was inhibited by approximately 68% after the 1‐hour attachment and by approximately 45% after the 4‐day attachment. Cell retention after the application of load was assessed by use of [3H]thymidine‐tagged chondrocytes and quantitation of the displacement of radioactivity. After the 1‐hour seeding period, loading induced a dose‐dependent dislodgment of [3H]radioactivity (as much as 35%) from the tissue bilayer. In contrast, after the 4‐day seeding period, there was no detectable effect of loading on chondrocyte dislodgment with an 8–12% release of radioactivity. The inhibitory effect of a 16‐hour compression of 0.48 MPa applied after the 4‐day seeding period was studied further. This protocol did not appear to have an irreversible effect on chondrocyte metabolism; at 2 days after the release of load, proteoglycan synthesis by the loaded cells was stimulated by 41% compared with transplanted cells that were not subjected to loading. These results suggest that the application of static compressive stress to chondrocytes at a cartilage surface may affect biosynthesis by these cells and thus subsequent integrative cartilage repair. Such an effect may have implications for optimization of the tightness of the press fit of a cell‐laden cartilaginous construct

ISSN:0736-0266    

DOI:10.1002/jor.1100160504

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

年代:1998

数据来源: WILEY

摘要:

AbstractAccording to numerous cadaveric, radiographic, and clinical studies, ankle and knee joints differ in susceptibility to osteoarthritis. To test for biochemical differences in susceptibility to damage, a chondrocytic chondrolysis system has been utilized. In this system, fibronectin fragments are added to cultured cartilage explants, resulting in enhanced release of catabolic cytokines. induction of matrix metalloproteinases, temporary suppression of proteoglycan synthesis, and consequently, severe loss of cartilage proteoglycan. We found that the addition of an amino‐terminal thrombin‐generated 29‐kDa fibronectin fragment to cultured knee cartilage from 14 donors (average age: 53 years) usually caused a 30–50% decrease in proteoglycan content by day 7. However, of the ankle cartilage specimens examined from 21 donors (average age: 50 years), only three showed damage by, day 7. one by day 14, and six by day 21. and 11 were not damaged until day 28. For eight of the donors (average age: 44 years), both knee and ankle cartilages were obtained; this allowed comparison between tissues from the same donor. The analysis showed that the ankle cartilage was much more refractory to damage than was the knee cartilage from the same donor. These data clearly show differences between ankle and knee cartilage in susceptibility to the fibronectin fragments and suggest the feasibility of use of these fragments for discerning differences in homeostasis of the ankle and knee ca

ISSN:0736-0266    

DOI:10.1002/jor.1100160505

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

年代:1998

数据来源: WILEY

摘要:

AbstractThe capability to reliably predict long‐termin vivowear of polyethylene would be of great value for the early identification of problematic total hip designs. Formal quantitative estimates of long‐term polyethylene wear were made from a series of 197 patients who had a total hip arthroplasty and who were followed for a minimum of 10 years; the estimates were based on the wear that was apparent radiographically at nominally 2 years after the operation. A newly developed digital image‐analysis edge‐detection procedure was applied to 1,237 archived follow‐up radiographs. The edge‐detection measurements were analyzed with a robust regression random‐coefficients statistical formulation developed especially to address the distributions of wear rate observed across this population over time. Formal regression equations were reported, which can be used to estimate late‐wear depth for a patient radiographed at a 2‐year follow‐up visit. Series wide, the correlation between predicted and observed wear depths was 0.73 at 4 years, with a correlation decline of approximately 0.03

ISSN:0736-0266    

DOI:10.1002/jor.1100160506

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

年代:1998

数据来源: WILEY

摘要:

AbstractTwo designs of total knee replacements were analysed to determine how the geometry of their bearing surface would affect the susceptibility of their ultra high molecular weight polyethylene tibial inserts to delamination. Orientations of the femoral components on the tibial surfaces were calculated with use of rigid body analysis for discrete intervals during the stance phase of gait. For each successive orientation, finite element analysis was used to compress the components together to determine the stresses in the tibial inserts. A damage function analogous to strain energy density was defined to account for the accumulated amplitudes, and frequencies of the maximum shear stress cycles and hence to predict fatigue failure. The damage function was applied to each polyethylene element in the tibial insert, and the highest value calculated for each design was its damage score. One knee had a damage score more than three times less than that of the other because of lower stresses and because the contact points moved in the medial‐lateral as well as anterior‐posterior directions during internal‐external rotation. The femoral and tibial components of this knee had lage outer frontal radii and close conformity in the frontal plane. We propose that this method, which accounts for the motions and stresses endured during walking, makes different predictions regarding the likelihood of delamination compared with the predictions made by conventional static compression tests performed when the knee is in a neutral pos

ISSN:0736-0266    

DOI:10.1002/jor.1100160507

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

年代:1998

数据来源: WILEY

摘要:

AbstractCurrent 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 prov

ISSN:0736-0266    

DOI:10.1002/jor.1100160508

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

年代:1998

数据来源: WILEY

摘要:

AbstractMany studies have shown enhanced bone apposition to implants coated with hydroxyapatite, but the optimum implant texture, especially in abnormal trabecular bone, is unclean The purpose of this project was to evaluate the histological and mechanical properties of cylindrical implants with three different surface textures that were placed in the cancellous bone of the distal femur of the rabbit after the production of an inflammatory knee arthritis. The three implant surfaces included a beaded surface (Group A), a beaded surface coated with hydroxyapatite (Group B), and a smooth surface coated with hydroxyapatite (Group C). The right knees of 36 rabbits were injected with carrageenan twice a week for 2 weeks. Then bilateral implantations were performed, with 12 rabbits in each group receiving identical implants in the right and left knees. The rabbits were killed 6 weeks after surgery. Mechanical (push‐out test) and histomorphometric analyses were performed to determine the quality and quantity of bone ingrowth. In Group A, there was virtually no direct contact (a 20–60‐μm clearance) between the bone and the beaded surfaces. Direct contact between the bone and the implant surfaces was seen in Groups B and C. The thickness and number of trabeculae were smaller on the arthritic side than on the control side for all groups but were not different between groups for either the control or the arthritic side. Mechanical testing showed that the shear strength of the interface was weaker on the arthritic side in all groups. The results suggest that inflammatory arthritis induced by carrageenan may influence the quality of local bone (osteopenic changes) and hence compromise the bone apposition and mechanical stability of the interface between the implant an

ISSN:0736-0266    

DOI:10.1002/jor.1100160509

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

年代:1998

数据来源: WILEY

摘要:

AbstractChondrosarcomas are alleged to be resistant to chemotherapy. A retrospective review of our experience primarily with dedifferentiated chondrosarcomas treated with chemotherapy was performed to re‐evaluate the efficacy of chemotherapy for this tumor. There were 18 patients: 14 stage IIB and four stage III. Seventeen patients had dedifferentiated chondrosarcoma. The median age at diagnosis was 57 years. Fourteen of the patients underwent wide excision of the tumor, two underwent amputation, and two had no surgery. The femur and the pelvis were the most common locations of the primary tumor. Chemotherapy for 11 of the patients consisted of cisplatin and doxorubicin. Survival was analyzed with the Kaplan‐Meier method; the median survival was 12 months. The hypothesis that chondrosarcomas express P‐glycoprotein was tested. Expression of P‐glycoprotein was evaluated by immunostaining with use of the C494 and C219 antibodies on 41 benign and malignant cartilage tumors, six of which were from the patients in the chemotherapy group. Immunostaining revealed that 37 of 41 cartilage tumors expressed P‐glycoprotein. The rate of survival of patients with high‐grade chondrosarcoma treated with chemotherapy is poor. P‐glycoprotein expression is common in benign and malignant cartilage lesions. The lack of response to chemotherapy may be related to the expression of P

ISSN:0736-0266    

DOI:10.1002/jor.1100160510

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

年代:1998

数据来源: WILEY

摘要:

AbstractThe Achilles tendon is one of the most common sites of injury and rupture as a result of overuse. Evidence suggests that the pathogenesis of rupture could involve the pattern of its blood supply. With use of angiographic and histological techniques, the blood supply of the Achilles tendon was investigated in 12 human cadaveric specimens. Angiography confirmed Mayer's 1916 finding that the blood supply to the tendon is from three areas: the musculotendinous and osseotendinous junctions and the paratenon, with the posterior tibial artery providing the major contribution. However, qualitative and quantitative histological analyses in this study showed that the Achilles tendon has a poor blood supply throughout its length, as determined by the small number of blood vessels per cross‐sectional area, which do not in general vary significantly along its length. In light of these findings, it is suggested that poor vascularity may prevent adequate tissue repair following trauma, leading to further weakening of the tendo

ISSN:0736-0266    

DOI:10.1002/jor.1100160511

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

年代:1998

数据来源: WILEY