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PubMed2003

Early osteoarthritic changes of human femoral head cartilage subsequent to femoro-acetabular impingement.

OBJECTIVE: To use the surgical samples of patients with femoro-acetabular impingement due to a nonspherical head to analyze tissue morphology and early cartilage changes in a mechanical model of hip osteoarthritis (OA). DESIGN: An aberrant nonspherical shape of the femoral head has been assumed to cause an abutment conflict (impingement mechanism) of the hip with subsequent cartilage lesions of the acetabular rim and surface alterations of the nonspherical portion of the head. In this study, 22 samples of the nonspherical portions of the head have been obtained during hip surgery from young adults (mean 30.4 years, range 19-45 years) with an impingement conflict. The samples were first compared with tissue from the same area obtained from six age-matched deceased persons (control group) with normal hip morphology and second with cartilage from 14 older patients with advanced OA. All samples were characterized histologically and hyaline cartilage was graded according to the Mankin criteria. They were further subjected to examination on a molecular basis by immunohistology for cartilage oligomeric matrix protein (COMP), tenascin-C and a collagenase cleavage product (COL2-3/4C(long)) and by in situ hybridization for collagen type I and collagen type II. RESULTS: All samples from the patient group revealed hyaline cartilage with degenerative signs. According to the Mankin criteria, the cartilage alterations were significantly different when compared with the control group (p=0.007) but were less distinct when compared with cartilage from patients with advanced OA (p=0.014). Positive staining and distribution pattern for COMP, tenascin-C and COL2-3/4C(long) showed similarities between the samples from the impingement group and osteoarthritic cartilage but they were distinctly different when compared with healthy cartilage. Levels of collagen I and II transcripts were upregulated in 6 and 10, respectively, of the 14 samples with OA and in 9 and 12, respectively, of the 22 samples from the impingement group. None of the samples from the control group showed upregulation of Collagen I and II mRNA. CONCLUSIONS: The aberrant nonspherical portion of the femoral head in young patients with an impingement conflict consists of hyaline cartilage which shows clear degenerative signs similar to the findings in osteoarthritic cartilage. The tissue alterations are distinctly different when compared with a control group, which substantiates an impingement conflict as an early mechanism for degeneration at the hip joint periphery.

Adult↗
PubMed1999

Biomechanics of integrative cartilage repair.

Cartilage repair is required in a number of orthopaedic conditions and rheumatic diseases. From a macroscopic viewpoint, the complete repair of an articular cartilage defect requires integration of opposing cartilage surfaces or the integration of repair tissue with the surrounding host cartilage. However, integrative cartilage repair does not occur readily or predictably in vivo. Consideration of the 'integrative cartilage repair process', at least in the relatively early stages, as the formation of a adhesive suggests several biomechanical approaches for characterizing the properties of the repair tissue. Both strength of materials and fracture mechanics approaches for characterizing adhesives have recently been applied to the study of integrative cartilage repair. Experimental configurations, such as the single-lap adhesive test, have been adapted to determine the strength of the biological repair that occurs between sections of bovine cartilage during explant culture, as well as the strength of adhesive materials that are applied to opposing cartilage surfaces. A variety of fracture mechanics test procedures, such as the (modified) single edge notch, 'T' peel, dynamic shear, and trouser tear tests, have been used to assess Mode I, II, and III fracture toughness values of normal articular cartilage and, in some cases, cartilaginous tissue undergoing integrative repair. The relationships between adhesive biomechanical properties and underlying cellular and molecular processes during integrative cartilage repair remain to be elucidated. The determination of such relationships may allow the design of tissue engineering procedures to stimulate integrative cartilage repair.

Animals↗
PubMed2001

Interindividual variability and correlation among morphological parameters of knee joint cartilage plates: analysis with three-dimensional MR imaging.

OBJECTIVE: To determine the range and variability of the cartilage volume, thickness, and articular surface areas in the knee joints of healthy male subjects, the association of these parameters within and between the knee joint cartilage plates, and their correlation with anthropometric variables. METHOD: The right knees of 27 individuals (age 23 to 64 years) without cartilage damage were examined. Sagittal magnetic resonance imaging was with a fat-suppressed gradient echo sequence (resolution 2 x 0.31 x 0.31 mm(3)), quantitative parameters being computed for all cartilage plates. RESULTS: The total knee joint cartilage volume ranged from 16.6 to 31.4 ml, the size of the articular surfaces from 102 to 163 cm(2), and the mean cartilage thickness from 1.57 to 2.43 mm. The mean and maximal cartilage thickness were highest in the patella (2.76 and 5.72 mm). There was a significant correlation of the cartilage volume with the mean thickness (R=0.80) and with the joint surface areas (R=0.56), but not between the thickness and surface area (R=0.37). The association among the patella, tibia, and femur was 0.16 to 0.72 for volumes, 0.08 to 0.78 for thickness, and 0.24 to 0.62 for surfaces. The knee joint cartilage volume and the surface areas were significantly associated with the body height (R=0.51 and 0.57), but not the cartilage thickness (R=0.22). CONCLUSION: There is a surprisingly high variability of the quantitative distribution of cartilage within the knee joint, with only moderate correlations between knee joint cartilage plates, and this variability cannot be adequately predicted based on anthropometric variables.

Adult↗
PubMed1997

Effect of impact load on articular cartilage: development of an intra-articular fracture model.

OBJECTIVES: To investigate the biological and mechanical effects of a single-impact load on articular cartilage. DESIGN: An in vitro laboratory study was performed using mature bovine cartilage and bone, and isolated cartilage explants. Each specimen was impacted with a single load applied with a specially designed impactor and materials test machine. Chondrocyte metabolic activity and cartilage structural integrity was investigated using force displacement curves, radionuclide labeling, histology, and changes in water content. SETTING: Laboratory for Soft Tissue Research, New York, New York, U.S.A. SPECIMENS: Viable mature bovine cartilage and cartilage and bone explants. MAIN OUTCOME MEASUREMENTS: Mechanical failure, proteoglycan synthesis, water content, histology, radiography, and scanning electron microscopy changes occurring during the twenty-four-hour period immediately following impact. RESULTS: Force/displacement curves for the cartilage and bone explants demonstrated two failure-stress peaks, the first at fifty megapascals, representing cartilage failure, and a second peak at seventy-five megapascals, representing bone failure. Fine grain radiographs, histology, and scanning electron microscopy all confirmed the destruction of the cartilage in the area of direct impact (zone I) and subchondral bone failure and the detachment of the cartilage within the lesser impacted area (zone II). Proteoglycan synthesis was reduced significantly (p < 0.05) in the areas of direct impact (zone I) compared with areas with less or no impact (zones II and III, respectively). Significantly greater water content (p < 0.05) was found within the cartilage of zone I compared with zones II and III. CONCLUSIONS: Significant and possibly irreversible articular cartilage damage occurs after a single high-energy impact load.

Animals↗
PubMed1998

Efficacy of perichondrium and a trabecular demineralized bone matrix for generating cartilage.

A pedicled auricular perichondrial flap wrapped around trabecular demineralized bovine bone matrix can generate an autologous cartilage graft. In earlier experimental studies, it was demonstrated that this graft could be used for nasal and cricoid reconstruction. It was assumed that the vascularization of the perichondrial flap was obligatory, but it was never proven that the flap should be pedicled. Moreover, for clinical use, the dimensions of the auricle would set restrictions to the size of the graft generated. Therefore, the possibility to generate cartilage with a composite graft of a free perichondrial flap wrapped around demineralized bovine bone matrix, by using young New Zealand White rabbits, was studied. This composite graft was implanted at poorly (subcutaneously in the abdominal wall; n = 12), fairly (subcutaneously in the pinna; n = 12), and well-vascularized sites (quadriceps muscle; n = 12). As a control, trabecular demineralized bovine bone matrix was implanted without perichondrial cover. Half of these grafts (n = 6) were harvested after 3 weeks, and the remaining grafts (n = 6) after 6 weeks of implantation. In histologic sections of these grafts, the incidence of cartilage formation was scored. Furthermore, the amount of newly formed cartilage was calculated by computerized histomorphometry. Trabecular demineralized bovine bone matrix without perichondrial cover demonstrated early resorption; no cartilage or bone was formed. In demineralized bovine bone matrix wrapped in perichondrium, early cartilage formed after 3 weeks at well- and fairly vascularized sites. No cartilage could be detected in grafts placed at a poorly vascularized site after 3 weeks; minimal cartilage formed after 6 weeks. In summary, the highest incidence of cartilage formed when trabecular demineralized bovine bone matrix was wrapped either in a pedicled auricular perichondrial flap or in a free perichondrial flap, which was placed at a well-vascularized site. Second, a significantly higher percentage of the total area of the graft was cartilaginized at well-vascularized sites after 3 weeks. The newly generated cartilage contained collagen type II and proteoglycans with hyaluronic acid binding regions, whereas collagen type I was absent, indicating the presence of hyaline cartilage. This study demonstrates that new cartilage suitable for a graft can be generated by free perichondrial flaps, provided that the site of implantation is well vascularized. Consequently, the size of such a graft is no longer limited to the dimensions of the auricle.

Animals↗
PubMed1987

Cartilage damage by a granulomatous reaction in a murine species.

The encapsulation of intact rat femoral head cartilage or discs of bovine nasal cartilage with cotton-gauze before implantation in the subcutaneous tissues of mice, results in an accelerated loss of cartilage proteoglycan. Loss of proteoglycan from bovine nasal cartilage occurred later than rat femoral head cartilage, but eventually brought about complete dissolution of the cartilage. Freeze-thaw killing of bovine nasal cartilage did not alter the amount of proteoglycan lost. Destruction of both femoral and nasal cartilage was related to the mass of cotton implanted and to the growth of connective tissue within the implanted cotton. Mice previously implanted with femoral head cartilage were able to show enhanced degradation to new implants; this was even greater if the original implants were encapsulated with cotton. Presoaking of cotton-cartilage implants with the non-specific irritant, carrageenan inhibited the breakdown of cartilage. Autoradiographs of 35sulphate pulsed femoral cartilage following implantation with cotton showed reduced incorporation of radiolabel by chondrocytes.

Animals↗
PubMed2006

In vitro enzymatic treatment and carbon dioxide laser beam irradiation of morphologic cartilage specimens.

OBJECTIVES: To determine the role of the main cartilage components in the internal system of interlocked stresses and to clarify the effect of laser beam irradiation on cartilage. DESIGN: Control and experimental series. SUBJECTS: Rabbit ear cartilage. INTERVENTION: Rabbit ear cartilage strips incubated in collagenase and hyaluronidase enzyme solutions for specific periods were examined, and the observed changes in shape, strength, and elasticity were recorded, as well as the effect of carbon dioxide laser irradiation. Laser-pretreated cartilage strips were also incubated in the enzyme solutions to determine whether the laser-provoked changes were susceptible to enzymatic action. All cartilage pieces were examined by light and electron microscopy. RESULTS: Collagenase-treated cartilage strips gradually lost their interlocked stresses, while hyaluronidase-treated strips mostly maintained their shape and their physical characteristics. Hyaluronidase-incubated cartilage strips altered their shape when they were laser treated. Collagenase-treated cartilages did not modify their shape when they were laser treated. Laser-pretreated cartilage pieces lost their new form in collagenase solutions but kept their laser-evoked shape when put in hyaluronidase solutions. CONCLUSION: The macroscopic observations combined with light and electron microscopy findings argue for the distinct role of the collagen network in morphologic cartilage shape and tensile strength preservation and provide a probable mechanism of cartilage transformation owing to carbon dioxide laser irradiation.

Animals↗
PubMed1998

Articular cartilage collagen birefringence is altered concurrent with changes in proteoglycan synthesis during dynamic in vitro loading.

INTRODUCTION: The articular cartilage collagen network and proteoglycans are subject to changes in deteriorating joint diseases. In this study, we exposed articular cartilage plugs to cyclic loading and investigated the properties of collagen network and proteoglycans in different zones of the articular cartilage. METHODS: Articular cartilage full-depth plugs were exposed in vitro to 4.1 MPa cyclic (0.5 Hz) loading for 1 to 20 hr and investigated using quantitative microscopic methods (i.e., polarized light microscopy, microspectrophotometry, and autoradiography). RESULTS: The loading caused packing or condensation of the tissue. In histological sections, the height of uncalcified articular cartilage decreased by an average of 12.8% (range, 4 to 19.7%). Loading increased the birefringence of collagen in the superficial cartilage (P < 0.05), with thickening of the zone up to 41.4% at 20 hr. The thickness of the intermediate zone increased also (22% at 1 hr and 434% at 20 hr). Concomitantly, the birefringence (P < 0.05) and the thickness of the deep zone decreased (18.5 to 27.8%). Loading for 4 hr increased the 35S-sulphate incorporation of the cartilage explants by an average of 67% (P < 0.05). The increase was most significant in the deep cartilage. A simultaneous increase was observed in the proteoglycan concentration of the cartilage; the staining intensity with safranin-O increased by 8.8% (P < 0.05). After 8 hr loading, this stimulation decreased; at 20 hr, loading caused a clear inhibitory effect on proteoglycan synthesis in the superficial zone. DISCUSSION: According to these results, the chosen loading regimen increased the thickness and collagen orientation in the superficial zone. In contrast, the thickness and birefringence in the deep cartilage were reduced. The proteoglycan metabolism of chondrocytes was first stimulated deep in the cartilage, but as the loading continued, the effect proved to be inhibitory (especially in the superficial part of uncalcified cartilage).

Animals↗
PubMed1996

Regional variations of indentation stiffness and thickness of normal rabbit knee articular cartilage.

The rabbit knee is frequently used as an experimental model for cartilage repair, but the choice of different joint regions for such studies makes comparisons between methods difficult. Furthermore, there is only limited information available about the regional variations of the biomechanical properties in normal rabbit knee articular cartilage. In the present study in situ indentation tests were used to map the short-term stiffness and thickness of articular cartilage at seven locations (anterior and posterior areas of the medial and lateral femoral condyles, the patellar groove, and the central areas of the medial and lateral tibial plateaus) in nine normal rabbit knee joints. Short-term cartilage stiffness was described by elastic moduli under ramp loading and 15-s creep conditions. The moduli were calculated according to Hayes' single-phase elastic model. A moderate positive correlation (r = 0.54) between cartilage stiffness and thickness was found for rabbit femoral cartilage, but was not confirmed for tibial cartilage, which had the thickest, but also the softest cartilage of all areas. The cartilage in the patellar groove and the medial compartments of both femoral condyles and tibial plateaus was stiffer and thicker than that in the lateral components, similar to previous findings in dogs. However, the dog femoral cartilage was found to be stiffer at the anterior than at the posterior regions, but we found the opposite in the rabbit. These dissimilarities between animal models may be caused by different joint loading characteristics. Accordingly, in rabbits repair processes in the more anterior femoral areas with less stiff cartilage may not be comparable to repairs in more posterior areas where cartilage is stiffer.

Animals↗
PubMed2001

Structural evaluation of articular cartilage: potential contribution of magnetic resonance techniques used in clinical practice.

OBJECTIVE: To determine whether routine magnetic resonance imaging (MRI) techniques can detect age-related structural modifications of bovine articular cartilage. METHODS: The cartilage of 3-month-old, 3-year-old, and 13-year-old animals was studied. T1- and T2-weighted MR sequences were performed using a 1.5T clinical imager and a 3-inch surface coil. Histologic slices (5 microm) of cartilage specimens were stained with picrosirius red (for collagen) and toluidine blue (for glycosaminoglycans [GAGs]). A polarized light study was performed to determine the collagen network organization. Except for the 13-year-old animal cartilage, the biochemical content was studied on slices cut parallel to the surface to determine GAG and hydroxyproline (collagen) content. Cartilage profiles were performed to determine the MR pixel intensity and the histologic color intensity. RESULTS: On T1-weighted images, the cartilage was homogeneous, with pixel intensity profiles presenting low variations. On T2-weighted images, the cartilage was laminar in the 3-month-old animals and became homogeneous thereafter. The pixel intensity varied through the cartilage depth with a profile that depended on the age of the animal. The collagen and GAG staining showed abrupt transitions in the 3-month-old animal, while in older animals the cartilage became more homogeneous with a mild gradient of matrix constituents with depth. These results were confirmed by findings of a biochemical study. In addition to these matrix content variations, the bovine cartilage presented modifications of its collagen network organization with aging. CONCLUSION: The MR T2-weighted sequences depicted signal variations with age in bovine cartilage concomitant with modifications in its structure. If confirmed in clinics, these observations will reinforce the place of MRI in characterizing cartilage with aging and pathologic processes.

Aging↗
PubMed2001

Age-related changes in the morphology and deformational behavior of knee joint cartilage.

OBJECTIVE: Alterations of cartilage morphology and mechanical properties occur in osteoarthritis, but it is unclear whether similar changes also take place physiologically during aging, in the absence of disease. In this in vivo study, we tested the hypothesis that thinning of knee joint cartilage occurs with aging and that elderly subjects display a different amount of cartilage deformation than do young subjects. METHODS: We evaluated 30 asymptomatic subjects ages 50-78 years. Morphologic parameters for the knee cartilage (mean and maximum thickness, surface area) were computed from magnetic resonance imaging data. Results were compared with those in 95 young asymptomatic subjects ages 20-30 years. Deformation of the patellar cartilage was determined after the subjects performed 30 knee bends. RESULTS: There was a significant reduction of patellar cartilage thickness in elderly women (-12%; P < 0.05), but not in elderly men (-6%). Femoral cartilage was significantly thinner in both sexes (-21% in women, -13% in men; P < 0.01), whereas tibial cartilage thickness displayed only nonsignificant trends (-10% in women, -7% in men). Patellar cartilage deformation was -2.6% in elderly women and -2.2% in elderly men. These values were significantly lower (P < 0.05) than those in young subjects. CONCLUSION: We confirmed the hypothesis that knee cartilage becomes thinner during aging, in the absence of cartilage disease, but that the amount of reduction differs between sexes and between compartments of the knee joint. We show that under in vivo loading conditions, elderly subjects display a lower level of cartilage deformation than do healthy young subjects.

Adult↗
PubMed2003

Effects of antiinflammatory drugs on arthritic cartilage: a high-frequency quantitative ultrasound study in rats.

OBJECTIVE: To evaluate the ability of 55-MHz quantitative ultrasound (US) to detect the in vivo effects of experimental arthritis, as well as those of two antiinflammatory drugs, naproxen (NPX) and dexamethasone (DEX), on cartilage and subchondral bone. METHODS: Arthritis was induced in both knees of 108 rats by intraarticular injection of zymosan (ZYM). Two groups of arthritic rats (n = 36 per group) were treated daily with either NPX (10 mg/kg/day) or DEX (0.1 mg/kg/day). Using a 3-dimensional US microscope, patellae were explored in vitro on days 5, 14, and 21 after injections. US assessment included the analysis of quantitative indices of local modifications involving cartilage and bone: integrated reflection coefficient (IRC) from the cartilage surface and apparent integrated backscatter from the cartilage internal structure (cartilage matrix) (AIB(cartilage)) and the cartilage-bone interface (AIB(bone)). RESULTS: ZYM induced articular surface fibrillation that resulted in a decrease in IRC at all times (P < 0.02) and in an increase in AIB(bone) on days 5 and 14 (P < 0.005). Fibrillation was not changed by NPX administration, while it disappeared following DEX treatment. Cartilage-bone interface alterations were prevented by DEX and partially compensated for by NPX. Cartilage matrix echogenicity decreased with time in all groups due to maturation (P < 0.05), except in DEX-treated rats. CONCLUSION: Quantitative 55 MHz US allowed detection of early cartilage and bone lesions due to experimental arthritis, and also allowed detection of the effects of antiinflammatory drugs. NPX seemed to have an effect on subchondral bone lesions, but not on cartilage. DEX appeared to repair articular surface and bone, but prevented animal growth and cartilage maturation.

Animals↗
PubMed1985

Autoantibody specificities of immune complexes sequestered in articular cartilage of patients with rheumatoid arthritis and osteoarthritis.

To define autoantibody specificities of immune complexes sequestered in articular cartilage of patients with rheumatoid arthritis and osteoarthritis, extracts were obtained from articular cartilage specimens from 16 patients with rheumatoid arthritis, 11 patients with osteoarthritis, and 6 normal controls. Radioimmunoassays of the extracts revealed that rheumatoid cartilage contained 37 times more IgM and 14 times more IgG than did normal cartilage extracts. In addition, osteoarthritic cartilage contained 3 times more IgM and IgG than the normal tissues. IgM rheumatoid factor was found in 13 of 16 rheumatoid cartilage extracts but in none of 11 osteoarthritic or 6 normal control extracts. IgG rheumatoid factor was detected in 4 of 7 seropositive rheumatoid but in none of 5 osteoarthritic cartilage extracts. More than 60% of the rheumatoid cartilage extracts were positive for native and denatured collagen II antibodies. Surprisingly, 50% of the osteoarthritic specimens also contained significant titers of collagen antibodies. Similar results were obtained with osteoarthritic menisci extracts. These findings indicate that the immune complexes sequestered in rheumatoid cartilage contain autoantibodies that are probably synthesized locally by cells infiltrating the inflamed synovium. If immune complexes trapped in cartilage play an important role in cartilage damage, our findings would provide a possible pathogenic mechanism that explains the self-perpetuating and chronic nature of cartilage degradation in rheumatoid arthritis and osteoarthritis.

Adult↗
PubMed1986

Composition and glycosaminoglycan metabolism of articular cartilage from habitually loaded and habitually unloaded sites.

The uronic acid (proteoglycan, PG) content of cartilage from habitually unloaded sites of normal canine femoral condyles has been shown to be lower than that from habitually loaded regions, even though the glycosaminoglycan (GAG) synthesis is similar. We investigated whether the GAG degradation in unloaded cartilage would be greater than that in loaded cartilage, and we obtained comparative biochemical data concerning the PGs and organization of the extracellular matrix of normal loaded and unloaded cartilage. PG extractability (determined by sequential guanidinium chloride extracts of cartilage), percentage of PGs forming large aggregates, and hydrodynamic size of the PG monomers (determined by Sepharose 2B chromatography) were essentially the same in loaded and unloaded cartilage. As expected, the uronic acid content of unloaded cartilage was 20% lower than that of loaded cartilage (P less than 0.02), while the water and DNA contents of the 2 tissues were not statistically different. There was no difference in the rate of net 35SO4-GAG synthesis in organ cultures of loaded and unloaded cartilage. Moreover, there was no appreciable difference in the rates of 35SO4-GAG degradation of loaded and unloaded cartilage, as determined by 35SO4 pulse-chase studies. We have previously shown that selective cyclic compressive stresses applied in vitro to cartilage from loaded areas of canine femoral condyles may increase 35SO4-GAG synthesis. The present results suggest that the rates of GAG metabolism in loaded and unloaded cartilage under atmospheric pressure in vitro may not reflect the rates which exist in articular joints under compressive loads in vivo.

Animals↗
PubMed2005

Role of interleukin-1 and tumor necrosis factor alpha in matrix degradation of human osteoarthritic cartilage.

OBJECTIVE: To determine whether interleukin-1 (IL-1) or tumor necrosis factor alpha (TNFalpha), or both, plays a role in the excessive degradation that is observed in cultured osteoarthritic (OA) articular cartilage. METHODS: Antagonists of IL-1 and TNFalpha, namely, IL-1 receptor antagonist and the PEGylated soluble TNFalpha receptor I, respectively, were added at different concentrations to explant cultures of nonarthritic (5 obtained at autopsy) and OA (15 obtained at arthroplasty) articular cartilage. The cleavage of type II collagen (CII) by collagenase was measured by an immunoassay in cartilage and culture media. Proteoglycan (mainly aggrecan) content and degradation were measured by a colorimetric assay for glycosaminoglycan (GAG) content in cartilage and culture media. Reverse transcriptase-polymerase chain reaction was used to analyze gene expression of matrix metalloproteases (MMPs) 1, 3, and 13, CII, aggrecan, IL-1, and TNFalpha. RESULTS: Antagonists of IL-1 and TNFalpha inhibited the increase in CII cleavage by collagenase as well as the increase in GAG release observed in OA cartilage compared with normal cartilage. Inhibition was significant in tissue from some patients but not from others, although significant inhibition was observed when all the results were analyzed together. An increase in the GAG content in cartilage was seen in 4 of 15 cases. However, this increase was not significant when all the data were combined. Preliminary results indicated no effect of these antagonists on nonarthritic cartilage from 3 different donors. Independent analyses of gene expression in cultured cartilage from 9 other OA patients revealed that IL-1 or TNFalpha blockade, either alone and/or in combination, frequently down-regulated MMP-1, MMP-3, and MMP-13 expression. Expression of IL-1 and TNFalpha was inhibited by either antagonist or by the combination in essentially half the cases. The combined blockade up-regulated aggrecan and CII gene expression in approximately half the cases. CONCLUSION: These results suggest that the autocrine/paracrine activities of TNFalpha and IL-1 in articular cartilage may play important roles in cartilage matrix degradation in OA patients but not in all patients. Inhibition of either or both of these cytokines may offer a useful therapeutic approach to the management of OA by reducing gene expression of MMPs involved in cartilage matrix degradation and favoring its repair.

Adult↗
PubMed2005

Inhibition of integrative cartilage repair by proteoglycan 4 in synovial fluid.

OBJECTIVE: To determine the effects of the articular cartilage surface, as well as synovial fluid (SF) and its components, specifically proteoglycan 4 (PRG4) and hyaluronic acid (HA), on integrative cartilage repair in vitro. METHODS: Blocks of calf articular cartilage were harvested, some with the articular surface intact and others without. Some of the latter types of blocks were pretreated with trypsin, and then with bovine serum albumin, SF, PRG4, or HA. Immunolocalization of PRG4 on cartilage surfaces was performed after treatment. Pairs of similarly treated cartilage blocks were incubated in partial apposition for 2 weeks in medium supplemented with serum and (3)H-proline. Following culture, mechanical integration between apposed cartilage blocks was assessed by measuring adhesive strength, and protein biosynthesis and deposition were determined by incorporated (3)H-proline. RESULTS: Samples with articular surfaces in apposition exhibited little integrative repair compared with samples with cut surfaces in apposition. PRG4 was immunolocalized at the articular cartilage surface, but not in deeper, cut surfaces (without treatment). Cartilage samples treated with trypsin and then with SF or PRG4 exhibited an inhibition of integrative repair and positive immunostaining for PRG4 at treated surfaces compared with normal cut cartilage samples, while samples treated with HA exhibited neither inhibited integrative repair nor PRG4 at the tissue surfaces. Deposition of newly synthesized protein was relatively similar under conditions in which integration differed significantly. CONCLUSION: These results support the concept that PRG4 in SF, which normally contributes to cartilage lubrication, can inhibit integrative cartilage repair. This has the desirable effect of preventing fusion of apposing surfaces of articulating cartilage, but has the undesirable effect of inhibiting integrative repair.

Animals↗
PubMed2006

Collagen and proteoglycan turnover in focally damaged human ankle cartilage: evidence for a generalized response and active matrix remodeling across the entire joint surface.

OBJECTIVE: Although cartilage lesions occur in the ankles, osteoarthritis rarely develops in the ankles, suggesting that ankle cartilage can up-regulate mechanisms to repair the damaged matrix. To define these processes, we compared cartilage samples obtained from normal tali and from lesional sites of damaged tali. METHODS: Cartilage samples were obtained from the tali of normal ankles and from 3 sites on tali with lesions (the lesion, adjacent to the lesion, and far removed from the lesion). Cartilage was analyzed for type II collagen (CII) messenger RNA, C-terminal type II procollagen propeptide (CPII), the collagenase cleavage neoepitope (Col2-3/4C(short)), and the denaturation epitope (Col2-3/4m). For the assessment of type IX collagen, the COL2 and NC4 domains were evaluated. The cartilage samples were also assayed for glycosaminoglycans, epitope 846 of aggrecan, and DNA. RESULTS: The DNA content, epitope 846, COL2(IX), and the denaturation epitope were significantly increased in lesional cartilage. Although there was a tendency toward an increase in CII content and CPII, the increase did not reach significance. Neither the NC4(IX) domain nor Col2-3/4C was elevated. Surprisingly, changes in cartilage both adjacent to and remote from the lesion were similar to those in the lesion. CONCLUSION: The changes observed in cartilage obtained from the lesion and from sites adjacent to the lesion were not surprising; however, the changes in cartilage obtained from sites remote from the lesion were unexpected. This up-regulation of matrix turnover in ankles with degenerative lesions may indicate a physiologic response of the entire articular surface to repair the damaged matrix, which is not restricted to the lesion site. This suggests that there may be some mechanism of communication across the cartilage. The response by ankle cartilage obtained from a site remote from the lesion has not been observed in the knee.

Adult↗
PubMed2007

Injecting partially digested cartilage fragments into a biphasic scaffold to generate osteochondral composites in a nude mice model.

This study proposed a novel scaffold with heterogeneous morphology that mimics the natural tissue. Its upper part contains a hollow cavity surrounded by a wall of poly(L-lactic-co-glycolic acid) (PLGA) porous membrane for injecting cartilage tissue and cells. An interconnecting porous structure located under the hollow cavity was made of composite materials that combined PLGA and beta-tricalcium phosphate (beta-TCP) to simulate the subchondral bone. Adult pig articular cartilage was cut and sieved into small fragments. The tissue fragments was partially digested by 0.1% collagenase for 0, 2, 4, and 6 h and injected into the hollow cavity of the biphasic scaffold. The biphasic scaffolds were then implanted into the subcutaneous pocket of nude mice for 4 weeks. No tissue bonding or new cartilaginous tissue formation was identified in the cartilage fragment without enzymatic treatment. The cartilage fragments digested with 2 h of collagenase digestion were partially integrated after implantation. The integrative properties of the cartilage fragment depended on the extent of enzymatic digestion. Releasing cells at the tissue surface enhanced confluence and bonding of the cartilage fragment matrix. Complete integration of the cartilage fragments and cartilage remodeling were achieved by digestion of the tissue fragments with 4 h of enzymatic treatment. The neocartilage grew from the upper hollow cavity into the lower PLGA/beta-TCP porous structure, forming an interface similar to that formed between cartilage and subchondral bone. This study combined the osteochondral scaffold and limited cartilage tissues to generate cartilage tissue in vivo intending for repairing full-thickness articular cartilage defects.

Animals↗