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Biomedical subjects

D Amiel

Publications and source records attributed to D Amiel.

At least 19 recordsLinked to original sources

Wrist and digital joint motion produce unique flexor tendon force and excursion in the canine forelimb.

The force and excursion within the canine digital flexor tendons were measured during passive joint manipulations that simulate those used during rehabilitation after flexor tendon repair and during active muscle contraction, simulating the active rehabilitation protocol. Tendon force was measured using a small buckle placed upon the tendon while excursion was measured using a suture marker and video analysis method. Passive finger motion imposed with the wrist flexed resulted in dramatically lower tendon force (approximately 5 N) compared to passive motion imposed with the wrist extended (approximately 17 N). Lower excursions were seen at the level of the proximal interphalangeal joint with the wrist flexed (approximately 1.5 mm) while high excursion was observed when the wrist was extended or when synergistic finger and wrist motion were imposed (approximately 3.5 mm). Bivariate discriminant analysis of both force and excursion data revealed a natural clustering of the data into three general mechanical paradigms. With the wrist extended and with either one finger or four fingers manipulated, tendons experienced high loads of approximately 1500 g and high excursions of approximately 3.5 mm. In contrast, the same manipulations performed with the wrist flexed resulted in low tendon forces (4-8 N) and low tendon excursions of approximately 1.5 mm. Synergistic wrist and finger manipulation provided the third paradigm where tendon force was relatively low (approximately 4 N) but excursion was as high as those seen in the groups which were manipulated with the wrist extended. Active muscle contraction produced a modest tendon excursion (approximately 1 mm) and high or low tendon force with the wrist extended or flexed, respectively. These data provide the basis for experimentally testable hypotheses with regard to the factors that most significantly affect functional recovery after digital flexor tendon injury and define the normal mechanical operating characteristics of these tendons.

Animals

The effects of hyaluronan on matrix metalloproteinase-3 (MMP-3), interleukin-1beta(IL-1beta), and tissue inhibitor of metalloproteinase-1 (TIMP-1) gene expression during the development of osteoarthritis.

OBJECTIVE: To assess the influence of intra-articular injection of hyaluronan (HA) on expression of matrix metalloproteinase-3 (MMP-3), interleukin-1beta(IL-1beta), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in cartilage and synovium during the process of osteoarthritis (OA). DESIGN: Eighteen mature New Zealand white rabbits underwent unilateral anterior cruciate ligament transection (ACLT) and were divided into two groups. The first group (HA injection group) received 0.3 ml of intra-articular HA injections into the ACLT knees 4 weeks after transection, once a week for 5 weeks as per clinical treatment presently utilized. The animals in the second group (no injection group) were not injected after ACLT. At death, 9 weeks following surgery, synovium and cartilage were harvested and total RNA was extracted. Gene expressions of MMP-3, IL-1beta and TIMP-1 were analyzed using reverse transcription-polymerase chain reaction (RT-PCR) for each subgroup created according to morphological grade of OA. RESULTS: The extent and grade of cartilage damage in the HA injection group was less severe than in the no injection group. In synovium, expression of MMP-3 and IL-1beta mRNA was suppressed in the mild grades of OA in the HA injection group. HA treatment had either no effect on MMP-3 expression in cartilage at all grades of OA or on enhanced MMP-3 and IL-1beta expression in synovium at a progressed grade. No effect of HA treatment on TIMP-1 expression was observed in either cartilage or synovium. CONCLUSIONS: These results suggest that one of the mechanism of therapeutic effect of HA is down-regulation of MMP-3 and IL-1beta in synovium during early development of OA.

Animals

Articular cartilage transplantation. Clinical results in the knee.

Between December 1983 and August 1991, 55 consecutive patients (55 knees) who underwent articular cartilage transplantation to their damaged knees were enrolled in the study. Average followup was 75 months (range, 11-147 months). Eight-two percent were younger than 45 years of age. Patients were evaluated through an 18-point scale, with 6 points each allocated to pain, range of motion, and function. An excellent knee was pain free, had full range of motion, and permitted unlimited activity. A good knee allowed full time employment and moderate activity. Eleven of 15 (73%) allografts transplanted 10 or more years ago were still good or excellent at the time of last followup. Overall, 45 of 55 (76%) knees that received the transplants were rated good or excellent. Specifically, 36 of 43 (84%) patients with unipolar transplants regained normal use of their resurfaced knee. The results after bipolar resurfacing were less encouraging, with only six of 12 (50%) knees rated good or excellent. The described technique of osteochondral shell allograft resurfacing of the knee capitalize on the different healing potentials of bone and cartilage by transplanting the viable articular cartilage organ in its entirety along with just enough of the underlying bone to allow for graft incorporation through creeping substitution. The results support the use of fresh osteochondral shell allograft transplantation for the treatment of large, full thickness articular cartilage defects to the medial or lateral femoral condyles and to the patella.

Adolescent

Chondrocyte apoptosis and nitric oxide production during experimentally induced osteoarthritis.

OBJECTIVE: Chondrocytes produce nitric oxide (NO) and undergo apoptosis in response to exogenous NO. This study sought to examine the relationship between NO synthesis, chondrocyte apoptosis, and the development of cartilage degradation during experimental osteoarthritis (OA). METHODS: OA was induced in rabbits by anterior cruciate ligament transection (ACLT). Knees were harvested after 4 weeks and assessed for OA severity and chondrocyte apoptosis. Conditioned media from cultured cartilage explants were analyzed for nitrite content. Cartilage sections were analyzed by immunohistochemistry for the presence of nitrotyrosine. RESULTS: All ACLT knees demonstrated osteoarthritic changes. Conditioned media from ACLT cartilage organ cultures contained higher levels of nitrite as compared with cartilage samples from the nonoperated side or from rabbits that had not received ACLT. Cultures of specific areas of cartilage from ACLT knees showed high levels of NO production in the medial femoral and medial tibial cartilage. Approximately 28.7% of chondrocytes isolated from ACLT cartilage and 6.7% of chondrocytes from cartilage of the nonoperated side underwent apoptosis. In situ staining demonstrated apoptotic cells in the superficial and middle zones of ACLT cartilage. A high number of apoptotic cells was present at the pannus-cartilage junction. In control cartilage, the superficial zone contained a small number of cells in apoptosis. The prevalence of apoptotic cells was significantly correlated with the levels of nitrite production and OA grade. CONCLUSION: These observations suggest that, during the early phases of OA, NO production may lead to chondrocyte apoptosis, and that both events contribute to the pathogenesis of cartilage degradation. Inhibitors of NO synthesis and chondrocyte apoptosis may therefore be of therapeutic value after cartilage injury and in patients with OA.

Animals

Age-related changes in the expression of cadherin-11, the mesenchyme specific calcium-dependent cell adhesion molecule.

Cadherin-11 is a calcium-dependent cell adhesion molecule that is expressed in cells of the mesenchymal lineage during embryonic development. In this study we show, for the first time, that cadherin-11 gene is expressed in the bone marrow and bone cells obtained from rabbits of various age groups. Furthermore, a quantitative measurement of gene expression revealed that cadherin-11 was expressed in young rabbits (6 week-old: open epiphysis) at a level of 6.7 x 10(5) +/- 0.7 x 10(5) molecules; in mature rabbits (8-10 month-old: closed epiphysis) at 11 x 10(5) +/- 0.9 x 10(5) molecules; and in aged rabbits (4-5 year-old) at a level of 1.2 x 10(5) +/- 0.2 x 10(5) molecules/microg total RNA. The relative level of cadherin-11 gene expression in mature rabbit marrow was found to be approximately 50% greater than in young rabbits. However, aged animals showed a reduction in cadherin-11 specific gene expression of greater than 900% as compared with mature animals. Age-related changes in bone remodeling/turnover lead to reduced bone density and high fracture risk, and since cadherins play a crucial role in tissue morphogenesis, this marked decrease may represent an index of the aging process in bone.

Age Factors

Architectural remodeling in deep frozen meniscal allografts after total meniscectomy.

This study assesses the biological characteristics of cell repopulation and matrix remodeling in deep frozen meniscal allografts after total meniscectomy and allograft transplantation. Thirty-two mature New Zealand White rabbits were operated on, and the allografts were assessed at 12 and 26 weeks postsurgery. Before transplantation, fresh medial menisci were placed into liquid nitrogen to kill all intrinsic cells. Frozen meniscal allografts showed collagen remodeling coincident with revascularization and cellular repopulation. Biochemical characterization showed active collagen remodeling of the allografts at 12 and 26 weeks. In situ hybridization showed that expression of types I and III procollagen mRNAs were increased at 12 weeks, especially near the region of the synovial capsule. At 26 weeks after transplantation, the pattern of collagen-type expression progressed toward normal; that is, type I procollagen mRNA expression was prominent, whereas only a small amount of type III procollagen mRNA was observed. These data indicate the adaptation of the repopulating cells from the host to the frozen allograft at 26 weeks after transplantation.

Animals

Long-term effects of hyaluronan on experimental osteoarthritis in the rabbit knee.

OBJECTIVE: Long-term assessment of the effect of hyaluronan (HA) on the articular cartilage and synovium in an animal knee joint during the development of osteoarthritis (OA). DESIGN: Sixty mature New Zealand white rabbits underwent unilateral anterior cruciate ligament transection (ACLT) and were divided into two groups. Group 1 (SA) received intra-articular injections of 0.3 ml hyaluronan (HA) (i.e., ARTZ, MW: 8 x 10(5)) beginning 4 weeks after ACLT, once a week for 5 weeks. Group 2 (SV) received injections of the vehicle (phosphate buffered saline) in the same fashion as with the SA group. The contralateral nonoperated knee served as control. All animals were killed 21 weeks after surgery and their knee joints evaluated by gross morphologic, histologic, histomorphometric and biochemical analyses. RESULTS: Gross morphological inspection indicated that the femoral condyles from the knees injected with vehicle suffered more severe cartilage damage than cartilage from the knees injected with HA. Furthermore, two out of three histomorphometric parameters measured in the HA-treated cartilage (i.e., cartilage thickness and cartilage area which were not statistically different than control) provided evidence showing a protective effect of HA on the femoral condyles following ACLT. Biochemical analysis showed articular cartilage remaining on the femoral condyles following ACLT to have similar characteristics to contralateral controls. However, DNA concentration in the synovium from the ACLT knees of the vehicle-treated animals was greater than contralateral control, while this parameter was not statistically different than contralateral control in the HA treated animals. CONCLUSIONS: These results demonstrate a protective effect of HA on preservation of the articulating surface of the femoral condyle following ACLT up to 21 weeks post-surgery.

Animals

Histomorphometric and biochemical effect of various hyaluronans on early osteoarthritis.

OBJECTIVE: To evaluate, histomorphometrically and biochemically, different protective effects of clinically used hyaluronans (HA). METHODS: An experimental osteoarthritis (OA) model was applied to 132 mature NZW rabbits by resecting the unilateral anterior cruciate ligament (ACL). The other knee, where ACL remained intact, served as the control. We used native HA with different molecular weights, HA-50 (MW 5-7.3 x 10(5)), HA-80 (MW 8 x 10(5)), HA-360 (MW 3.6 x 10(6)), and crosslinked HA (HA-CL). HA were injected into the joint once a week for 5 weeks (HA-50, HA-80, HA-360) or 3 weeks (HA-CL) beginning 4 weeks after ACL transection. Histomorphometric and biochemical assessment was performed 9 weeks post-transection for both the HA treated and nontreated groups. RESULTS: In gross morphological observation, cartilage degeneration was suppressed in HA treated groups, and this effect was superior in the groups receiving either HA-80 or HA-CL. Histomorphometric and biochemical analyses of the articular cartilage revealed similar results: the HA-80 and HA-CL groups showed no significant differences between the ACL transection and the control knees by histomorphometric variables, while the nontreated groups revealed significant degeneration. These evaluations were done in unblinded fashion. Biochemical analyses, including DNA synthesis in the synovium, also showed that articular cartilage and synovium in the HA-80 and HA-CL groups did not present significant changes compared to controls. CONCLUSION: In quantitative evaluation of this short term study using the OA model, native HA-80 and HA-CL presented a superior cartilage protective effect compared to the other native HA.

Animals

Growth factor expression in healing rabbit medial collateral and anterior cruciate ligaments.

Exogenously administered growth factors such as platelet-derived growth factor (PDGF), transforming growth factor beta (TGF-beta) and basic fibroblast growth factor (bFGF) have been shown to affect connective tissue healing in vivo, but their intrinsic role in the healing response has not been established. In the present study, immunohistochemistry with antibodies directed against these growth factors showed that expression of PDGF, TGF-beta 1 and bFGF was increased in and around the wound site in the rabbit medial collateral ligament (MCL) seven days following surgical injury. The strong expression of PDGF correlated with the observed increased cellularity consistent with this growth factor's mitogenic and chemotactic properties. Expression of these growth factors was also increased in wounded rabbit anterior cruciate ligaments (ACL) at seven days following surgical injury, but such expression was limited to the edge of the ACL injury site and was of lesser intensity relative to the MCL. This study suggests that PDGF and TGF-beta 1, and to a lesser extent bFGF, are actively involved during the early stage of MCL healing, but have a more limited presence in the injured rabbit ACL.

Animals

Physical properties of rabbit articular cartilage after transection of the anterior cruciate ligament.

The effect of unilateral transection of the anterior cruciate ligament on the confined compression and swelling properties of the distal femoral articular cartilage of skeletally mature rabbits at 9 weeks after surgery was determined. Gross morphological grading of the transected and contralateral control distal femora stained with India ink confirmed that cartilage degeneration had been induced by ligament transection. Osteochondral cores, 1.8 mm in diameter, were harvested from the medial femoral condyles. The modulus, permeability, and electrokinetic (streaming potential) coefficient of the articular cartilage of the osteochondral cores were assessed by confined compression creep experiments. The properties (mean +/- SD) of control cartilage were: confined compression modulus, 0.75 +/- 0.28 MPa; hydraulic permeability, 0.63 +/- 0.28 x 10(-15) m2/Pa*sec; and electrokinetic coefficient, 0.16 +/- 0.31 x 10(-9) V/Pa. In transected knees, the modulus was reduced by 18% (p = 0.04), while the permeability and electrokinetic coefficient were not detectably altered. The change in modulus was accompanied by a trend (p = 0.07) toward a decrease (-11%) in the glycosaminoglycan density within the tissue, a significant increase (p < 0.001) in the water content of the cartilage after equilibration in 1 x phosphate buffered saline from 70.3 +/- 4.1% in control knees to 75.2 +/- 4.0% in transected knees, and little further swelling after tissue equilibration in hypotonic saline. The compressive modulus of the cartilage from both control and transected knees was positively correlated with the density of tissue glycosaminoglycan. The alterations in the physical properties of the articular cartilage after transection of the anterior cruciate ligament in the rabbit show trends similar to those observed in human and other animal models of osteoarthritis and provide further support for the use of this model in the study of cartilage degeneration.

Animals

Method of histomorphometric assessment of glycosaminoglycans in articular cartilage.

A method of image analysis has been developed for use in the semiquantitative histomorphometric assessment of glycosaminoglycans in articular cartilage stained with safranin O. The reliability of the methodology is reported along with its application to the assessment of articular cartilage in a model of osteoarthritis, i.e., transection of the anterior cruciate ligament in rabbits. With this system, specimens of normal and osteoarthritic articular cartilage were assessed histomorphometrically for the following parameters: total cartilage area, percentage of safranin O stained area, mean gray scale (average stain intensity), and gray scale index (the relative total amount of glycosaminoglycans). Reproducibility was established for 12 specimens of normal cartilage and found to have a SD of less than 8% of the mean for each parameter that was measured. Image analysis of osteoarthritic cartilage revealed each of the parameters, except for average stain intensity, to be significantly lower than that in control cartilage.

Animals

Chondrogenic phenotype of perichondrium-derived chondroprogenitor cells is influenced by transforming growth factor-beta 1.

Our laboratory has developed a method for the repair of osteochondral defects by implanting cultured perichondrial cells attached to a biodegradable polylactic acid scaffold. The success of this approach depends in part on the proliferative characteristics and the phenotype of the implanted cells. Transforming growth factor-beta 1 has been reported to influence these parameters in several mesenchymal-derived tissues in vitro and in vivo. The chondrocytic phenotype is marked by an enhanced expression of the collagen type-II gene. In this study, cultures grown from explants of rabbit rib perichondrium were exposed to exogenously added transforming growth factor-beta 1 at concentrations of 0.1-10 ng/ml of media. Cell proliferation and collagen gene expression were measured. The expression of types I and II collagen genes was analyzed by Northern blot and reverse transcriptase-polymerase chain reaction. The exogenous addition of transforming growth factor-beta 1 at a concentration of 0.1-10 ng/ml resulted in tritiated thymidine uptake by perichondrial cells, with optimum proliferative effects at 0.1 ng/ml. Transforming growth factor-beta 1 added at concentrations of 0.1 and 0.5 ng/ml significantly upregulated the expression of type-II collagen mRNAs. The results suggest that, when the chondrocytic phenotype is defined by markedly enhanced type-II collagen gene expression, the chondrocytic phenotype of explant cultures of perichondrium-derived cells is enhanced by the exogenous addition of transforming growth factor-beta 1.

Animals

The effects of hyaluronan during the development of osteoarthritis.

Ninety-nine mature New Zealand White (NZW) rabbits underwent unilateral anterior cruciate ligament transection (ACLT) and were divided into three groups. The contralateral non-operated knees served as controls. The first group (SA) received intra-articular injections of 0.3 ml hyaluronan (HA: MW; 8 x 10(5)) beginning 4 weeks after ACLT, once a week for 5 weeks. The second group (SV) was injected with vehicle (carrier of HA) in the same fashion as the SA group. The third group (SN) served as a nontreatment group post ACLT. All animals were killed 9 weeks post-surgery and were assessed by gross morphology, histomorphometry and biochemical analysis. Gross morphologic changes on the femoral cartilage in the SA group were less severe than those in the SV and SN groups. Cartilage thickness, cartilage area, and thickness of synovial lining cell layer histomorphometric parameters were measured, showing a positive effect of HA on the preservation of articular cartilage and synovial tissue. Similarly, the cartilage and synovial tissues from knees injected with HA did not demonstrate significant alterations from contralateral controls as measured by biochemical analysis [i.e., water content, pyridinoline concentration, glycosaminoglycan (GAG) content for the cartilage, and DNA concentration for the synovial tissue].

Animals

Analysis of heat shock proteins and cytokines expressed during early stages of osteoarthritis in a mouse model.

OBJECTIVE: Osteoarthritis (OA) is a debilitating disease of the joints. The joints of affected individuals are characterized by a progressive degeneration of articular cartilage leading to inflammation and pain. The expression of heat shock proteins (HSPs) is a ubiquitous self-protective mechanism of all cells under stress, furthermore, the synovium of osteoarthritic individuals contains high levels of cytokines. This study seeks to establish the role of HSPs and cytokines in OA. METHODS: We have investigated the presence of HSPs and cytokines in articular cartilage during early stages of OA in a mouse that is known to develop spontaneous OA lesions (C57 black mouse). The articular cartilage from closely related mice (C57BL/6) was used as control. Messenger RNAs (mRNAs) for HSPs (HSP32, HSP47, HSP60, HSP70, HSP84 and HSP86) and cytokines [interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma)] were detected by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The mRNA levels of HSP47, HSP70, HSP86, IL-6, and IFN-gamma were up-regulated in the cartilage of C57 black mice, whereas, the level of expression of HSP32, HSP60, HSP84 and IL-1 beta remained unchanged. Furthermore, the expression of IL-1 beta, IL-6, TNF-alpha and IFN-gamma mRNA was associated with expression of HSP60, HSP47, HSP70 and HSP70/HSP86 mRNA, respectively. CONCLUSIONS: The findings in this study suggest that chondrocytes are conditioned under non-physiological stress during early stages of OA, In addition, among HSPs, HSP70 was associated with two different highly expressed cytokines in C57 black mice, indicating the possible role of HSP70 as a characteristic indicator of early stage of OA.

Animals

Quantitation and localization of cartilage degeneration following the induction of osteoarthritis in the rabbit knee.

OBJECTIVE: To develop and apply a new video imaging technique to quantify and localize Indian ink staining of cartilage of the rabbit femorotibial joint after the induction of osteoarthritis by unilateral transection of the anterior cruciate ligament (ACLT). METHODS: Nine weeks after surgery, femora and tibiae from 11 ACLT and contralateral control knees were harvested and positioned to obtain calibrated gray-scale images of the ink-painted articular cartilage surfaces that are opposed with the knee in 90 degrees flexion. Images were processed so that areas of normal cartilage gave a relatively high reflectance score, whereas ink-stained fibrillated cartilage and exposed bone gave low scores. RESULTS: Comparison of the medial and lateral femoral condyles and tibial plateaus (MFC, LFC, MTP, LTP) of control and ACLT knees showed that the area of the MTP not covered by the meniscus had a significantly lower reflectance score (P < 0.001) than other areas. ACLT led to an 11% decrease (P < 0.001) in the overall reflectance score. The reflectance score decreased as a traditional morphological grading of degeneration increased. ACLT-induced degeneration had a predilection for the posteromedial aspects of the joint, and to a lesser extent, the anterolateral aspects. In the tibial plateaus, ACLT caused significant degeneration in the covered, but not the uncovered, areas. Image scores of opposing cartilage surfaces (i.e., MFC vs MTP and LFC vs LTP) were significantly (R = 0.56-0.70, P < 0.001) correlated in ACLT and control knees. DISCUSSION: Identification and characterization of cartilage areas prone to degeneration may be particularly useful for further analysis of biochemical and biomechanical mechanisms in osteoarthritis, as well as the efficacy of therapeutic interventions.

Animals

Osteochondral repair using perichondrial cells. A 1-year study in rabbits.

Articular cartilage repair remains a clinical and scientific challenge with increasing interest focused on the transplantation of chondrogenic cells. This study evaluated the repair response during a 1-year period after implantation of allogenic perichondrium cell polylactic acid composite grafts into 3.7 x 5 mm osteochondral defects drilled into the medial femoral condyles of 82 adult New Zealand White rabbits. The repair tissue was evaluated grossly, histologically, histomorphometrically, biochemically, and biomechanically at 6 weeks, 12 weeks, 6 months, and 1 year after implantation. After gross evaluation, cartilaginous material appeared to fill the defect in 70 experimental knees, for an overall repair frequency of 85%. The histomorphometric results and the histologic appearances were variable. None of the specimens were completely normal at 1 year. Only specimens with subchondral bone reformation displayed a definable cartilage appearing surface with chondrocytes surrounded by dense matrix. Subchondral bone reformation was inconsistent, reaching 50% at 1 year. Biochemically, the repair tissue matured during a 1-year period into a hyaline Type II collagen dominant tissue, whereas glycosaminoglycan content remained low at all time periods. The measured compressive properties of the repair tissue at 1 year were not significantly different from those of the contralateral knee that was not surgically treated. The treatment of osteochondral defects in the rabbit knee with allogenic perichondrium cell polylactic acid composite grafts yielded a high percentage of grossly successful repairs that showed inconsistent subchondral bone reformation. These results suggest that healthy subchondral bone is important to articular cartilage repair. They also highlight that a cartilaginous appearing tissue at gross inspection may not represent structurally normal articular cartilage. Continued multidisciplinary studies on the arthroplastic potential of rib perichondrial cells are needed before human studies, which rarely can extend beyond gross assessment of repair tissue appearance can be undertaken.

Animals

Decrease in fibronectin occurs coincident with the increased expression of its integrin receptor alpha5beta1 in stress-deprived ligaments.

Stress deprivation secondary to immobilization leads to atrophic changes in periarticular soft tissues. The changes in ligaments include a disorganization of collagen and cellular ultrastructure with varied biochemical alterations resulting in a functionally weaker tissue. This study tests the hypothesis that alterations in fibronectin (Fn) and the expression of its integrin receptor alpha5beta1 in ligament fibroblasts accompany the extracellular matrix remodeling which occurs in stress-deprived knee ligaments. The left knees of eighteen New Zealand white rabbits were surgically immobilized in acute flexion. Fibroblasts within three nine week and three twelve week stress-deprived anterior cruciate ligaments (ACLs) and medial collateral ligaments (MCLs) demonstrated markedly increased immunostaining for the beta1 and alpha5 integrin subunits, as compared to fibroblasts in the contralateral unoperated control ligaments. The effects of stress deprivation on the concentration of Fn was measured by competitive ELISA on the remaining twelve rabbits. Decreases in Fn of 54.0 percent and 63.7 percent occurred in the ACL after nine and twelve weeks of stress deprivation when compared to contralateral controls. The MCL had less of a decrease, losing 37.7 percent and 41.7 percent at nine and twelve weeks, respectively. These results suggest an important role for the Fn-specific integrin receptor alpha5beta1 in remodeling stress-deprived periarticular ligamentous tissue, and the importance of maintaining normal stresses on periarticular ligaments to prevent the degradation of extracellular matrix components such as Fn.

Animals