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PubMed1994

Role of oxygen radicals and IL-6 in IL-1-dependent cartilage matrix degradation.

It has been suggested that IL-1 produces cartilage matrix degradation by metalloproteinases such as collagenase and that such degradation is regulated by metalloproteinase inhibitors. In the present study, the effects of IL-6 and oxygen radical scavengers on cartilage matrix degradation were studied. Superoxide dismutase, catalase, or methionine all significantly inhibited cartilage matrix degradation both in IL-1 beta-stimulated and unstimulated experimental conditions. Both 10 mM EDTA and 100 nM tissue inhibitor of metalloproteinase (TIMP) significantly inhibited cartilage matrix degradation. The addition of methionine significantly inhibited collagenase activity produced in the culture supernatants of chondrocytes stimulated with IL-1 beta. IL-6 significantly suppressed cartilage matrix degradation produced spontaneously or by IL-1 beta stimulation in chondrocytes. IL-6 inhibited superoxide production by chondrocytes both in IL-1 beta-stimulated or unstimulated conditions. These results suggest that oxygen radicals are involved in cartilage matrix degradation mediated by both paracrine and autocrine IL-1 mechanisms and that oxygen radical-mediated activation of collagenase in chondrocytes may explain the mechanisms of how oxygen radicals are involved in cartilage matrix degradation. IL-6 inhibited superoxide production in chondrocytes and thus inhibited cartilage matrix degradation.

Arthritis, Rheumatoid↗
PubMed1986

The effect of anti-rheumatic drugs on factors from porcine synovium inducing chondrocyte mediated cartilage degradation.

A selection of NSAID's and diphosphonates were studied in a tissue culture model of cartilage degradation utilising porcine synovium and bovine nasal cartilage. All the NSAID's significantly reduced cartilage degradation when incorporated into the synovial culture medium. Lesser reductions were recorded when preformed chondrocyte stimulating factors were used and NSAID's added at the cartilage assay stage. These findings suggested that the principle site of action of NSAID's is upon the production of chondrocyte stimulating factors. None of the NSAID's tested affected inherent cartilage degradation. Diphosphonates had the opposite effects, they increased inherent cartilage degradation but had no effect on chondrocyte mediated cartilage degradation. The relationship of these results to previous known effects of NSAID's and diphosphonates upon cartilage is discussed. In addition, correlations between chondrocyte stimulating factors, catabolin and interleukin 1 are made.

Animals↗
PubMed1996

Plasminogen modulation of IL-1-stimulated degradation in bovine and human articular cartilage explants. The role of the endogenous inhibitors: PAI-1, alpha 2-antiplasmin, alpha 1-PI, alpha 2-macroglobulin and TIMP.

The studies described here examine the involvement of the fibrinolytic cascade and its endogenous inhibitors in the regulation of activity of matrix metalloproteinases and cartilage degradation related to non-inflammatory joint disease, like osteoarthritis. An interleukin-1-induced model of degradation using [35S]-labeled bovine and human articular cartilage explants was utilized. One goal of these studies was to compare the responses of bovine and human articular cartilage. Degradation was not inhibited by alpha 1-PI, PAI-1, alpha 2-macroglobulin, alpha 2-antiplasmin or TIMP-2, when IL-1 alone was added. Addition of human plasminogen to bovine explants, at concentrations found in human synovial fluid, increased degradation by three to four-fold. Under these conditions, the degradation was inhibited effectively by all of the endogenous inhibitors tested, indicating the presence of a cascade where activated chondrocytes are a source of u-PA. Plasminogen activated by u-PA gives plasmin, which is known to further activate pro-stromelysin. Stromelysin is essential for activation of collegenase. Not only TIMP, but also inhibitors at earlier steps of activation like PAI-1, alpha 2-antiplasmin, alpha 1-PI and alpha 2-macroglobulin inhibited degradation, and could provide cartilage protection in vivo. An experiment with human articular cartilage explants showed that very little or no degradation occurred when human articular cartilage explants were stimulated with interleukin-1 alone. Addition of human plasminogen (at physiologically relevant concentrations) resulted in significant degradation, which was inhibited in the same manner as in bovine explants, by inhibitors of the fibrinolytic cascade and TIMP. TIMP is much more efficient in human explants, indicating the limited participation of human plasmin in the degradation of human cartilage. Although speculative, it is possible that in vivo, cartilage degradation could be promoted not only by TIMP/MMP imbalance, but also accelerated by decreased levels of certain serpins in synovial fluid (e.g. PAIs, alpha 2-antiplasmin and alpha 1-PI).

Animals↗
PubMedDate not supplied

Biomechanical topography of human ankle cartilage.

The material properties of normal cadaveric human cartilage in the ankle mortice (tibiotalar articulation) were evaluated to determine a possible etiologic mechanism of cartilage injury of the ankle when an obvious traumatic episode is not present. Using an automated indentation apparatus and the biphasic creep indentation methodology, creep indentation experiments were performed in five sites in the distal tibia, one site in the distal fibula, and eight sites in the proximal talus of 14 human ankles (seven pairs). Results showed significant differences in the mechanical properties of specific human ankle cartilage regions. Topographically, tibial cartilage is stiffer (1.19 MPa) than talar cartilage (1.06 MPa). Cartilage in the anterior medial portion of the tibia has the largest aggregate modulus (HA = 1.34 MPa), whereas the softest tissue was found to be in the posterior lateral (0.92 MPa) and the posterior medial (0.92 MPa) regions of the talus. The posterior lateral ridge of the talus was the thickest (1.45 mm) and the distal fibula was the thinnest (0.95 mm) articular cartilage. The largest Poisson's ratio was found in the distal fibula (0.08). The lowest and highest permeability were found in the anterior lateral regions of the astragalus (0.80 x 10(-15) m4N-1sec-1) and the posterior medial region of the tibia (1.79 x 10(-15) m4N-1sec-1), respectively. The anterior and posterior regions of the lateral and medial sites of the tibia were found to be 18-37% stiffer than the anatomically corresponding sites in the talus. The biomechanical results may explain clinically observed talar dome osteochondral lesions when no obvious traumatic event is present. Cartilage lesions in a repetitive overuse process in the ankle joint may be related to a disparity of mechanical properties between the articulating surfaces of the tibial and talar regions.

Adolescent↗
PubMed1991

Arthritis induced immunologically with cationic amidated bovine serum albumin in the guinea pig. A morphological and biochemical study on the destruction of articular cartilage.

Arthritis was induced by injecting cationic amidated bovine serum albumin (aBSA) (pI approximately 9.2) into the knee joint of immunized guinea pigs and the mechanisms of articular cartilage destruction were studied morphologically and biochemically. Marked synovitis associated with polymorphonuclear leukocyte (PML) infiltration occurred within 1 day of the challenge. Articular cartilage infiltrated by PMLs was almost completely destroyed after 2 weeks. During the initial destructive process, proteoglycans were depleted from the cartilage and later collagen fibers disappeared. Granulation tissue growing in the inflamed synovium and bone marrow replaced the destroyed cartilage and joint cavity and formed fibrous scar tissue (fibrous ankylosis) by 8 weeks. Subsequently, the knee joints developed cartilagenous ankylosis by 12 weeks and finally bony ankylosis at 28 weeks. Autoradiography using 125I-aBSA and immunofluorescence studies for immunoglobulin (IgG) and complement (C3) demonstrated that the antigen is trapped in all zones of the articular cartilage and serves as a trigger for immune complex formation. Significantly increased neutral proteinase activities against substrates of proteoglycan subunits, [3H]carboxymethylated transferrin and L-pyroglutamyl-L-prolyl-L-valine-paranitroanilide were detected in homogenates of the synovium and cartilage from arthritic knee joints 1 and 2 weeks after induction. Inhibitor studies and pH curves suggested that the proteinase is leukocyte elastase. Measurable amounts of gelatinolytic activity, detected by activation with 4-aminophenylmercuric acetate and inhibited with EDTA, were also present in the same samples, but there was no detectable collagenase activity. The data on SDS-gelatin substrate gel showed that the proteinase is gelatinase derived from PMLs. These results suggest that in aBSA-induced arthritis, elastase and gelatinase from PMLs invading articular cartilage may play important roles in cartilage destruction.

Amino Acid Sequence↗
PubMed2003

Neoepitopes as biomarkers of cartilage catabolism.

Progressive degradation of articular cartilage is a central feature of arthritis and a major determinant of long term joint dysfunction. There are no treatments able to halt the progression of cartilage destruction presently available, and monitoring the benefit of potential therapies is hampered by our inability to measure the "health" of articular cartilage. Serial radiographic assessment of joint space narrowing, the current gold standard, requires measurements over a prolonged time (1-5 years) and is prone to technical difficulties. Other strategies for evaluating cartilage degradation are needed to enable both short and long term monitoring of disease progression and response to therapy. One avenue that holds promise is the use of biomarkers that accurately reflect the degradative state of the articular cartilage. Antibodies that recognise terminal amino acid sequences generated by proteolysis at specific sites in the core protein of both aggrecan and type II collagen (neoepitope antibodies) have become available in recent years. These antibodies have been invaluable for identifying the proteinases responsible for cartilage breakdown both in vitro and in vivo. The presence of neoepitope sequences generated by specific metalloenzyme cleavage of aggrecan and type II collagen correlates well with the progression of cartilage degeneration, both in vitro and in mouse models of arthritis. Preliminary results with quantitative assays of type II collagen neoepitopes suggest that they may be useful markers of joint disease in humans. Long term studies correlating neoepitope concentration with clinical and radiographic disease are now required to validate the utility of neoepitopes as surrogate markers of cartilage degeneration and joint disease.

Animals↗
PubMed1999

Noncollagenous, nonproteoglycan macromolecules of cartilage.

Extracellular matrix comprises approximately 90% of cartilage, with collagens and proteoglycans making up the bulk of the tissue. In recent years, several abundant cartilage proteins that are neither collagens nor proteoglycans have been characterized in detail. The putative roles of these proteins range from involvement in matrix organization or matrix-cell signaling (PRELP, chondroadherin, cartilage oligomeric protein and cartilage matrix protein) through to molecules that are likely to be involved with modulation of the chondrocyte phenotype (CD-RAP, CDMPs, chondromodulin and pleiotrophin). Other molecules, such as the cartilage-derived C-type lectin and cartilage intermediate layer protein have no role as yet. Due to the difficulties associated with experimentally manipulating a tissue that is 90% extracellular matrix in a manner that can be readily transferred to the whole organism, many of these molecules have been focused on by a surprisingly small number of researchers. This review focuses on newly discovered proteins and glycoproteins in cartilage, with a bias towards those that have structural roles or that are unique to cartilage.

Animals↗
PubMed2002

[Basic principles and surgical technique of tibio-fibula-plasty in cartilage-bone transplantation].

BACKGROUND: Within the last few years autologous cartilage-bone-grafting is becoming an established standardized procedure in joint surgery. One significant disadvantage of this technique is the harvesting of the bone plugs from the weight-bearing area of the knee joint. PURPOSE: The tibiofibular articulation is located close to the knee joint that is operated on. This articulation is covered with cartilage. The purpose of this study was to evaluate the question, whether this joint is suitable as a donor site for bone-cartilage transplants. MATERIAL AND METHODS: Favourable approaches and committing of anatomical landmarks were investigated on 44 fixed tibiofibular joints. In knee extension, the shortest distance between the joint cleft and common fibular nerve was measured. The cartilage thickness and histology of both the fibular and tibial joint surface were documented. The developed surgical approach was evaluated in patients. RESULTS: Histological and immunohistochemical examination showed hyaline cartilage and type II collagen. The average cartilage thickness was 1.9 +/- 0.29 mm (minimum: 1.5 mm; maximum: 2.6 mm). The peroneal nerve showed an average distance to the tibiofibular joint of 24 mm (minimum: 12 mm; maximum: 30 mm). Different surgical procedures are possible and clinical relevant. CLINICAL RELEVANCE: The tibiofibular joint contains cartilage, which may be a reasonable donor site even for the elderly patient. Harvesting the graft from this area may avoid iatrogenic damaging of intraarticular weight bearing cartilage of the knee joint.

Aged↗
PubMed2006

Cartilage viability after trochleoplasty.

Trochleoplasty is an established and accepted technique for the treatment of patellar instability because of a missing trochlear groove. In this technique, a flap of cartilage over the trochlea is carefully removed and a new trochlear groove is created in the underlying bone before the cartilaginous flap is reattached with sutures. The mid-term clinical and radiological results of this operation are promising but no information about the viability of the reattached cartilage has been reported. To evaluate cartilage viability and quality after trochleoplasty and to verify the healing process, two osteochondral biopsies were harvested from three patients 6, 8, and 9 months after trochleoplasty. One cylinder was evaluated histologically to assess cartilage, calcified cartilage (cc), and subchondral bone quality, while the other one was examined by confocal microscopy to evaluate cell viability. The histological examination showed a normal matrix and cell distribution of the cartilage, while the cc showed lacunae ingrowing from the underlying bone. The subchondral bone showed normal lamellae and histology, and the healing of the flap. Confocal microscopy showed almost exclusively viable chondrocytes. This demonstration of non-injured cartilage at short-term follow-up together with promising clinical and radiological 2- and 5-year follow-up results indicate a potential promising outlook for the long term, as further chondral damage is not expected. So trochleoplasty can be seen as a primary intervention for patellar instability because of trochlear dysplasia as the risk for cartilage damage is low.

Adolescent↗
PubMed1997

Comparison of in vitro response to growth hormone by chondrocytes from mandibular condyle cartilage of young and old mice.

In several aspects the features of aging resemble those of the state of growth hormone (GH) deficiency. Alterations of bone density and increased incidence of osteoporosis are some of the characteristics of aging that are similar to the findings in GH-deficient adults. Osteoarthritis (OA), a nonfatal condition predominating in old age, is characterized by the slowly progressive destruction of articular cartilage of joints. OA lesions are observed in the temporomandibular joint of ICR mice aged 7 months and older. The aim of the present study was to compare the response of chondrocytes from mandibular condyle cartilage of young and old mice to GH and to ascertain whether chondrocytes of old animals could still be stimulated to proliferate and to synthesize matrix components under the direct effect of GH in vitro. Mandibular condyles from young (3-month-old) and old (20-month-old) female ICR mice were cultured up to 72 hours in the presence of recombinant rat GH (0.1-100 ng/ml). 3H-Thymidine and 35S-sulfate were introduced during the last 24 hours of culture. Administration of GH appeared to increase only slightly the incorporation of 3H-thymidine in cartilage from young compared with the response in cartilage from old animals which was much more significant at 24 hours and 48 hours in culture. The same pattern was seen for the effect of GH on the incorporation of 35S-sulfate. Cartilage from young animals responded only slightly to GH, whereas a significant response was observed in cartilage from old animals after 24 and 48 hours in vitro. DNA contents were significantly elevated at all time intervals in both old and young animals, yet more significantly in cultures from old animals. In contrast, the activities of both alkaline and acid phosphatases were elevated at all time intervals in cultures from young animals, whereas no induction was observed in cultures from old animals. Tissue sections from cultures of old animals treated with GH (10 ng/ml, 48 hours) revealed atypical hypertrophic cells along the articular surface and also dark staining along the cartilage-bone interface. Exposure to tetracycline (10 mg/ml, 24 hours) resulted in an induced fluorescence, indicating enhanced mineralization in this region. Results of this study indicate that mandibular condyle cartilage from OA old mice responds in vitro to the addition of GH via anabolic activities of cell proliferation, sulfated proteoglycan synthesis, and possibly enhanced mineralization.

Aging↗
PubMed2003

MR appearance of cartilage defects of the knee: preliminary results of a spiral CT arthrography-guided analysis.

The aim of this study was to determine signal intensity patterns of cartilage defects at MR imaging. The MR imaging (3-mm-thick fat-suppressed intermediate-weighted fast spin-echo images) was obtained in 31 knees (21 male and 10 female patients; mean age 45.5 years) blindly selected from a series of 252 consecutive knees investigated by dual-detector spiral CT arthrography. Two radiologists determined in consensus the MR signal intensity of the cartilage areas where cartilage defects had been demonstrated on the corresponding reformatted CT arthrographic images. There were 83 cartilage defects at spiral CT arthrography. In 52 (63%) lesion areas, the MR signal intensity was higher than that of adjacent normal cartilage with signal intensity equivalent to (n=31) or lower than (n=21) that of articular fluid. The MR signal intensity was equivalent to that of adjacent normal cartilage in 17 (20%) lesion areas and lower than that of adjacent cartilage in 8 (10%) lesion areas. In 6 (7%) lesion areas, mixed low and high signal intensity was observed. The MR signal intensity of cartilage defects demonstrated on spiral CT arthrographic images varies from low to high on fat-suppressed intermediate-weighted fast spin-echo MR images obtained with our equipment and MR parameters.

Adolescent↗
PubMed2001

MR microscopy of hyaline cartilage: current status.

Cartilage degenerative diseases, such as osteoarthritis, affect million of people. Magnetic resonance imaging is presently the most accurate imaging modality in evaluating the state of hyaline cartilage; however, clinical MRI does not accurately reveal early degenerative alterations in cartilage, due mainly to low spatial resolution. Magnetic resonance microscopy (MRM, or microMRI) appears exceptionally well suited to the in vitro or ex vivo study of this heterogeneous tissue, due to its high spatial resolution; however, despite this, further studies are necessary to evaluate the potential of MRM in the detection of early cartilage damage. Herein we briefly review the current applications of MRM in the study of hyaline cartilage. In particular, we review the MR appearance of hyaline cartilage on high-resolution images, the different MRM techniques used to image normal and enzymatically or chemically degraded cartilage and the potential use of contrast agents. The future directions and the relevance of MRM findings for a better understanding of cartilage physiology in health and disease are also discussed.

Cartilage, Articular↗
PubMed2005

The morphology and biomechanical characteristics of subcutaneously implanted tissue-engineered human septal cartilage.

The purpose of the study was to examine the morphology and biomechanical characteristics of in vivo cultured tissue-engineered human septal cartilage as a prospective autogenous transplant material for subcutaneous implantation in reconstructive procedures. Chondrocytes were enzymatically isolated from human septal cartilage biopsies. The cell number was expanded in monolayer culture. Chondrocytes were then fixed on a non-woven poly-lactide-poly-glycolide (PGLA) polymer scaffold by means of fibrin glue. The PGLA-polymer construct was implanted subcutaneously on the back of athymic mice and allowed to mature for 6 or 12 weeks. After killing the mice, the formed cartilage was tested on a material testing machine with a highly standardized reproducible setting. Biomechanical testing consisted of an indentation test, which revealed the failure load and compressive modulus of the neocartilage. The failure load shows the upper limit of supported stress. The compressive modulus is a measure of the templates' stiffness. After testing, the templates were histologically stained. Native human septal cartilage served as a control group. Histological and macroscopic examination showed cartilage formation of a hyaline-like morphology. Histological staining revealed the synthesis of abundant mucopolysaccharid matrix. The biomechanical characteristics of neocartilage proved to be of no statistical difference compared to native human septal cartilage. The failure load and compressive modulus were initially somewhat lower and reached the control group's results after 12 weeks in-vivo. Summarizing, tissue engineered nasal cartilage matches typical mechanical characteristics of native hyaline cartilage. Its elasticity and failure load are of sufficient quality to meet the clinical requirements for reconstructive surgery.

Animals↗
PubMed2004

Cartilage canals in the chicken embryo: ultrastructure and function.

In this study the detailed morphology and the function of cartilage canals in the chicken femur are investigated. Several embryonic stages (e 13.5, 16, 19, and 20) are examined by means of light microscopy, electron microscopy (TEM), and immunohistochemistry (VEGF, type I and II collagen). Our results show that cartilage canals originate from the perichondrium and form a complex pattern. Two types of canals are distinguishable: shell canals and communicating canals. Shell canals are in the reserve zone and are arranged in successive layers. Communicating canals spring from the shell canals and pass down into the proliferative zone and into the hypertrophic zone. These canals are conical shaped and are orientated nearly in parallel to the long axis of the femur. Cartilage canals comprise venules, arterioles, capillaries (mature and immature), and undifferentiated mesenchymal cells. No canal wall in the sense of an epithelium is elaborated. VEGF is detected in both types of canals and macrophages are found at the end of the cartilage canals. We conclude that the growth factor stimulates angiogenesis and that the latter cells erode the matrix ahead of the canals and thus enable the advancement of the vessels. The results clearly show that the canal matrix differs from the remaining cartilage matrix. The canal matrix contains type I collagen, few type II collagen fibrils and proteoglycans are lacking. In contrast, in the cartilage matrix type II collagen and proteoglycans are abundant but no type I collagen is found. Communicating canals are surrounded by a distinct layer of type I collagen indicating that osteoid is formed around these canals. Hypertrophic chondrocytes label for type I collagen and it seemed possible that chondrocytes adjacent to the communicating canals differentiate into bone-forming cells. Our results provide evidence that cartilage canals are involved in nourishment of the cartilage as well as in the ossification process.

Animals↗
PubMed1998

Type X collagen is not localized in hypertrophic or calcified cartilage in the developing rat trachea.

Our previous studies have shown that rat tracheal chondrocytes become larger and hypertrophic, and that the cartilage matrix calcifies during development. Type X collagen is a short collagen molecule identified in hypertrophic and calcified cartilage in the growth plate of long bones during endochondral ossification. The present study was designed to investigate the distribution of type X collagen in rat tracheal cartilage during development before and after hypertrophization and calcification. Tracheas from postnatal Wistar rats, newborn, and at 4, 8 and 10 weeks were fixed along with hind limbs from newborn rats. Serial sections were made and adjacent sections were processed for von Kossa staining or immunohistochemistry for type X collagen. In addition, the immunoreactivity to type II collagen was examined as a control. The anti-type X collagen antibody stained hypertrophic and/or calcified cartilage in the newborn rat tibia. The immunoreaction for type X collagen was localized in the uncalcified peripheral region of tracheal cartilage in 4, 8 and 10-week-old rats. In contrast, the anti-type X collagen antibody did not show immunoreactivity to hypertrophic or calcified cartilage in the central region of the 10-week-old rat tracheal cartilage. The present study has suggested that type X collagen is not involved in hypertrophization of chondrocytes or calcification of the matrix in developing rat tracheal cartilage.

Animals↗
PubMed2006

Contributions of matrix metalloproteinases toward Meckel's cartilage resorption in mice: immunohistochemical studies, including comparisons with developing endochondral bones.

The middle portion of Meckel's cartilage (one of four portions that disappear with unique fate) degrades via hypertrophy and the cell death of chondrocytes and via the resorption of cartilage by chondroclasts. We have examined the immunolocalization of matrix metalloproteinase-2 (MMP-2), MMP-9, MMP-13, and MMP-14 (members of the MMP activation cascade) and galectin-3 (an endogenous substrate for MMP-9 and an anti-apoptotic factor) during resorption of Meckel's cartilage in embryonic mice and have compared the results with those of developing endochondral bones in hind limbs. MMP immunoreactivity, except for MMP-2, is present in nearly all chondrocytes in the middle portion of Meckel's cartilage. On embryonic day 15 (E15), faint MMP-2-immunoreactive and intense MMP-13-immunoreactive signals occur in the periosteal bone matrix deposited by periosteal osteoblasts on the lateral surface, whereas MMP-9 and MMP-14 are immunolocalized in the peripheral chondrocytes of Meckel's cartilage. The activation cascade of MMPs by face-to-face cross-talk between cells may thus contribute to the initiation of Meckel's cartilage degradation. On E16, immunopositive signaling for MMP-13 is detectable in the ruffled border of chondroclasts at the resorption front, whereas immunostaining for galectin-3 is present at all stages of chondrocyte differentiation, especially in hypertrophic chondrocytes adjacent to chondroclasts. Galectin-3-positive hypertrophic chondrocytes may therefore coordinate the resorption of calcified cartilage through cell-to-cell contact with chondroclasts. In metatarsal specimens from E16, MMPs are detected in osteoblasts, young osteocytes, and the bone matrix of the periosteal envelope, whereas galectin-3 immunoreactivity is intense in young periosteal osteocytes. In addition, intense MMP-9 and MMP-14 immunostaining has been preferentially found in pre-hypertrophic chondrocytes, although galectin-3 immunoreactivity markedly decreases in hypertrophic chondrocytes. These results indicate that the degradation of Meckel's cartilage involves an activation cascade of MMPs that differs from that in endochondral bone formation.

Acid Phosphatase↗
PubMed2000

Synthesis of mRNAs for cathepsins L and K during development of the rat mandibular condylar cartilage.

Cathepsins are cysteine proteinase family members which are known to degrade proteoglycan and collagen, components of several extracellular matrices. Their functions in the condylar cartilage during skeletal development have not yet been fully clarified. In this study, we investigated the mRNA expression of cathepsins L and K in the growing rat mandibular condylar cartilage, as compared to that in the rat long bone cartilage, by in situ hybridization, reverse transcription polymerase chain reaction (RT-PCR) and Southern blotting analysis. In the condylar cartilage, cathepsin L mRNA expression was widely observed throughout the zones of maturative and hypertrophic chondrocytes at embryonic day (E) 17 and postnatal day (P) 1. The signal was restricted to maturative and upper hypertrophic chondrocytes at P7, and finally it became undetectable by P28. In the long bone cartilage, cathepsin L was not expressed in the chondrocytes at any stage. Cathepsin K mRNA was not, however, detected either in the mandibular condylar cartilage cells or in the long bone cartilage cells but it was selectively detected in osteoclasts in calcified cartilage and bone in both tissues. RT-PCR also showed a similar mRNA expression pattern of cathepsins L and K. These results indicate that cathepsins L and K may be involved in the skeletal development of both the long bone and the mandibular condyle. Furthermore, cathepsin L may play an important role in the degradation of the cartilaginous extracellular matrix in maturative and hypertrophic cell layers during successive developmental stages of the mandibular condyle.

Animals↗
PubMed2000

Apoptosis of articular chondrocytes in rheumatoid arthritis and osteoarthritis: correlation of apoptosis with degree of cartilage destruction and expression of apoptosis-related proteins of p53 and c-myc.

To investigate the relationship of chondrocyte apoptosis and cartilage destruction, we performed in situ nick end labeling (ISNEL), electron microscopy, and immunohistochemistry against apoptosis-related proteins, p53 and c-myc, in the articular cartilages of patients with rheumatoid arthritis (RA; n = 12) and osteoarthritis (OA; n = 12), and in control articular cartilages from patients with femoral neck fracture (n = 8). The distribution of stained chondrocytes was evaluated semiquantitatively in relation to the degree of cartilage destruction. ISNEL-positive chondrocytes with apoptotic morphological features were identified in a relatively early phase of cartilage destruction, and correlated positively and significantly in a number with the degree of cartilage degeneration. Comparison of RA and OA revealed a significantly greater number of ISNEL-positive chondrocytes in RA cartilage. In contrast, the specimens of normal subjects contained few cells with apoptotic changes. Similarly to the distribution of ISNEL staining, the expression of p53 and c-myc proteins was observed in chondrocytes within the degraded lesions, and showed a positive correlation with the number of ISNEL-stained cells. These results suggest that the degree of chondrocyte apoptosis is closely related to cartilage destruction and that chondrocytes in RA more readily undergo apoptosis than those in OA. The expression of p53 and c-myc proteins in ISNEL-positive areas may reflect the involvement of these proteins in the apoptotic process in articular chondrocytes in inflammatory arthritis.

Adult↗