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At least 307 records · Page 17Linked to original sources
PubMed2001

Implication of cartilage intermediate layer protein in cartilage destruction in subsets of patients with osteoarthritis and rheumatoid arthritis.

OBJECTIVE: To investigate whether cartilage intermediate layer protein (CILP), a protein recently cloned from human articular cartilage, is recognized as an autoantigen in patients with osteoarthritis (OA) and rheumatoid arthritis (RA), and whether the immune response against CILP is involved in disease pathogenesis. METHODS: Recombinant fusion proteins, which contain the first half (C1), second half (C2), or 3 fragments within the C2 region (designated C2F1, C2F2, and C2F3) of the non-porcine nucleotide pyrophosphohydrolase-homologous region of CILP, were prepared using Escherichia coli. Autoantibodies to these proteins in serum samples from patients with OA or RA and from age-matched healthy individuals were detected by enzyme-linked immunosorbent assay and Western blotting. In addition, mice were immunized with a mixture of the C1 and C2 fusion proteins to assess the arthrogenicity of CILP. RESULTS: Production of antibodies to the C2 region was detected in 10.5% (11 of 105) of the tested OA patients and in 8.0% (7 of 88) of the tested RA patients, although antibodies to the C1 region were rarely detected in either patient group. All C2F1, C2F2, and C2F3 fragments were found to carry autoepitopes. The C2F2 fusion protein was recognized most frequently in the tested OA patients, whereas the C2F3 fusion protein was dominantly recognized in the tested RA patients. All 4 mice strains, DBA/1J, ICR, C57BL/6, and BALB/c, immunized with the CILP fusion proteins developed chronic arthritis; in particular, the ICR mice developed polyarthritis that was characterized by infiltration of mononuclear cells in the synovium and exfoliation of the surface of cartilage. CONCLUSION: The immune response to CILP may play a role in the pathogenesis of inflammatory joint destruction. Our results support the role of an immune-mediated process in the joint destruction present in chronic arthropathies such as OA and RA. The results suggest that suppression of immune responses to various components of the cartilage, such as CILP, might be therapeutically beneficial in these chronic arthropathies.

Adult↗
PubMed1997

Suppression of cartilage matrix gene expression in upper zone chondrocytes of osteoarthritic cartilage.

OBJECTIVE: To evaluate the anabolic activity of osteoarthritic chondrocytes in situ by investigating the messenger RNA (mRNA) expression of 3 major cartilage components, type II collagen, aggrecan, and link protein: METHODS: In situ hybridization experiments and histochemical analysis for proteoglycan content were performed on parallel sections of normal and osteoarthritic (OA) cartilage specimens. RESULTS: Most chondrocytes in the deeper.zones of OA cartilage showed an increase in mRNA expression, in particular, of type II collagen and to a lesser extent, aggrecan, compared with normal specimens. However, chondrocytes of the upper zone were largely negative for aggrecan or type II collagen mRNA. The expression of link protein mRNA was low in normal and OA specimens. CONCLUSION: These observations suggest that suppression of the anabolic activity of chondrocytes in the upper zones contributes to the metabolic imbalance observed in OA cartilage. Stimulation of matrix anabolism in superficial chondrocytes might be a suitable target for therapeutic intervention.

Aged↗
PubMed1991

Cartilage synthesizes the serine protease inhibitor PAI-1: support for the involvement of serine proteases in cartilage remodeling.

The work described here demonstrates the synthesis by human articular cartilage of plasminogen activator inhibitor-1 (PAI-1), a potent inhibitor of the serine protease tissue plasminogen activator (tPA). We also present data demonstrating an increase in PAI-1 messenger ribonucleic acid (mRNA) in chondrocytes exposed to the cytokine interleukin-1 (IL-1). Interestingly, this elevation of steady-state mRNA levels does not appear to result in an increase in synthesis of PAI-1 protein. Northern blot analysis reveals that of the two mRNA species (3.4 kb, 2.4 kb) previously reported for PAI-1, only the larger species (3.4 kb) appears to be synthesized by chondrocytes. Our data demonstrate the IL-1-stimulated production by cartilage of tissue plasminogen activator. We also show evidence for the presence of plasminogen in cartilage. A scheme is presented indicating the probable importance of the serine proteases (tPA and plasminogen) and PAI-1 in cartilage degradation.

Blotting, Northern↗
PubMed1993

Pleiotrophin is an abundant protein in dissociative extracts of bovine fetal epiphyseal cartilage and nasal cartilage from newborns.

An abundant protein that is identical to the growth-associated protein pleiotrophin (PTN) has been isolated from dissociative extracts of bovine nasal and fetal epiphyseal cartilage. The yield from these tissues was at least 15 micrograms/g wet weight of cartilage. PTN was absent or was present only in trace amounts in mature articular cartilage. An analysis of tryptic fragments of PTN, held together with disulfide bonds, did not indicate any set pattern of cystine cross-links, which suggests a propensity for rapid refolding of the protein. PTN could not be isolated from thin (10 microns) slices of nasal cartilage in physiological extraction buffers, which indicates that it was tightly associated with the cell surface, was tightly associated with nonextractable matrix, or was an intracellular protein. Its appearance in various extraction media parallels that of histone H2b, a nucleosomal protein; this suggests a possible intracellular location for the protein. Immunohistochemical analysis of its distribution in fetal epiphysis indicated that it is associated with chondrocytes.

Amino Acid Sequence↗
PubMed2002

A multivalent assay to detect glycosaminoglycan, protein, collagen, RNA, and DNA content in milligram samples of cartilage or hydrogel-based repair cartilage.

The biochemical measure of success in assisted cartilage repair is normally judged by repair tissue cell density, mRNA and protein expression, and accumulation of extracellular matrix molecules. Existing methods to solubilize cartilage matrix proteoglycans and cellular DNA for quantification, such as papain digestion, often destroy one or more species of the above-named parameters, in order to render others measurable. We have therefore developed a methodology to measure specific levels of mRNA, protein, DNA, glycosaminoglycan, and collagen content on single pulverized 10-mg samples of cartilage, or tissue-engineered cartilage, using successive extractions in concentrated guanidine hydrochloride (GuCl) and guanidine thiocyanate (GITC) solutions. Conditions were developed to solubilize most cellular proteins, DNA, proteoglycans, and some matrix proteins with an initial GuCl extraction step. A subsequent extraction with GITC was essential to solubilize the majority of the cellular RNA. Guanidine-insoluble material was rendered soluble by papain digestion, to enable quantification of collagen, residual glycosaminoglycan, and residual unextracted DNA in individual samples. In general, total collagen, GAG, and DNA content measured in multivalent-extracted samples was similar to that obtained with samples digested directly with papain. Moreover, we were able to reliably detect, in these same multivalent extracts, expressed mRNA as well as specific cellular and extracellular matrix proteins. This multivalent assay could be applied to a variety of cells cultured in biopolymers and to tissues from which biochemical components may be otherwise difficult to extract.

Animals↗
PubMed1990

Experimental studies on half-joint transplantation. Antigenicity of fresh allografted articular cartilage and changes in the articular cartilage.

This study was undertaken to examine the fate of articular cartilage in isogenic half-joint grafts implanted after storage by two-stage freezing. The antigenicity was evaluated quantitatively with regard to humoral and cellular immunological responses: none was seen in allogenic cartilage grafts. In the half-joint transplantations, the antigenicity of the cartilage need not be considered; only the antigenicity of cortical and cancellous bone must be reduced. Histologically, half-joint grafts stored at -196 degrees C were superior to fresh allografts. Two-stage freezing, therefore, appears to be useful for the storage of articular cartilage.

Animals↗
PubMed1994

Exclusion of the cartilage link protein and the cartilage matrix protein genes as the mutant loci in several heritable chondrodysplasias.

The chondrodysplasias are characterised by the abnormal development of articulating joints and bone. Mutations in the COL2A1 and COL10A1 genes, which encode the cartilage collagens type II and type X, have been identified in a variety of inherited chondrodysplasias. However, both genes have also been excluded as the mutant loci in several chondrodysplasia pedigrees, indicating the existence of at least one other chondrodysplasia locus. We report the exclusion of the genes encoding two cartilage-specific proteins, the cartilage link protein and the cartilage matrix protein, in several chondrodysplasia pedigrees in which COL2A1 had previously been excluded as the mutant locus.

Cartilage Oligomeric Matrix Protein↗
PubMed1990

Metabolic activity in the calcified zone of cartilage: observations on tetracycline labelled articular cartilage in human osteoarthritic hips.

The tidemark is a metabolically active zone in the calcified layer of the cartilage in which it is possible to show that there is calcifying activity even over a short period of time using a tetracycline labelling technique. The tidemark slowly advances in the direction of the non-calcified cartilage and analysis of double-tetracycline labelled cartilage shows that this is not an appositional phenomenon like that occurring in bone, but that, where present, several tidemarks can be labelled at the same time. Each tidemark may therefore be metabolically active and it is not just the tidemark adjacent to hyaline cartilage which incorporates calcium.

Bone Development↗
PubMed1997

Ultrastructural immunolocalization of cartilage oligomeric matrix protein (COMP) in porcine growth cartilage.

Cartilage oligomeric matrix protein (COMP) is a macromolecule of yet unknown function with restricted distribution among tissues. In the present study, the ultrastructural localization of COMP in porcine immature joint cartilage and growth plate cartilage was semiquantitatively delineated. Tissues were fixed in a mixture of low concentration glutar- and paraformaldehyde, embedded at low temperature, and subjected to immunocytochemistry using polyclonal antibodies raised against bovine COMP. Protein A-coated colloidal gold was used for detection. The most intense immunolabeling for COMP was noted in the proliferative zones of the growth cartilages. Here the concentration of immunomarker was higher in the territorial compartment than in the pericellular and interterritorial areas. A low concentration of COMP was observed in the resting and hypertrophic zones. The immunolabeling for COMP did not differ between the three matrix compartments of these zones. Supported by previous data obtained by in situ hybridization, the concentration of immunolabeling in the proliferative zone indicates a high rate of COMP synthesis in proliferative chondrocytes. Hence, COMP may be considered as a marker for normal differentiation into proliferative chondrocytes.

Animals↗
PubMed2005

Macroscopic and radiological grading of osteoarthritis correlates inadequately with cartilage height and histologically demonstrable damage to cartilage structure.

INTRODUCTION: The aim of the present study was to investigate different methods for determining osteoarthritis-related (OA) cartilaginous changes. MATERIALS AND METHODS: Human tibial heads were investigated radiologically, macroscopically and microscopically. The height of the hyaline cartilage was measured with the aid of a computerised digital image analysis system. RESULTS: The comparison of the different evaluation systems revealed, in part, appreciable variations in severity and produced correlations of r=-0.312-0.673. In none of the methods was a linear correlation between the histomorphometrically measured decrease in cartilage height and the increasing grade of OA evident. DISCUSSION: The microscopic scores are superior, since they provide the most precise description of cartilaginous structure. The variation in cartilage height with increasing OA is not a linear process; measurement of the cartilage height alone is not a valid parameter for determining the grade of OA.

Aged↗
PubMed1999

[Cartilage oligomeric matrix protein (COMP): the role of a non-collagen cartilage matrix protein as a marker of disease activity and joint destruction in patients with rheumatoid arthritis and osteoarthritis].

UNLABELLED: Today, we can assess criteria to predict the tissue destruction and progression of Rheumatoid Arthritis (RA) and Osteoarthritis (OA) only in a late stage of the disease. It would be an advantage to have biochemical markers of disease activity and joint destruction to optimize therapy. PATIENTS AND METHODS: In this cross-sectional study with 37 RA and 20 OA patients (disease duration 119 +/- 130 months for RA and 41 +/- 73 months for OA), ESR, CRP, disease activity score (DAS), the functional status of RA (American College of Rheumatology), and the radiological scoring systems of Larsen and Kellgren/Lawrence, respectively, were used as parameters for disease activity and joint destruction. Cartilage oligomeric matrix protein (COMP) was measured with an enzyme-linked immunosorbent assay (ELISA) in serum and synovial fluid, COMP fragments with immunoblot in the synovial fluid. RESULTS: The mean COMP value in synovial fluid was 38 ug/ml (RA) and 46 ug/ml (OA); 6.5 ug/ml (RA) and 3.4 ug/ml (OA) in serum. RA patients had a higher amount of small COMP fragments in synovial fluid than OA patients. In RA patients, there was a significant positive correlation between disease activity (DAS) and COMP in synovial fluid and serum, a negative correlation between functional status of RA and serum COMP and between radiologic joint destruction of the knee and serum COMP. In OA patients, there was a significant correlation of joint space width and synovial fluid COMP. DISCUSSION: A high clinical disease activity (DAS) correlated with high COMP values in serum and synovial fluid and with increasing proteolytic activity (higher amount of small COMP fragments especially in RA). An increased turnover of cartilage matrix in joint inflammation might explain this correlation. The correlation of decreased COMP with decreased functional status in RA and increased joint destruction is compatible with a loss of cartilage and less turnover. The correlation between joint space width and increased COMP in OA patients with short disease duration might be explained with a higher turnover of the cartilage matrix in the early stage of the disease.

Adult↗
PubMed2002

Pathogenesis of cartilage calcification: mechanisms of crystal deposition in cartilage.

Apatite crystals form in physiologically calcified tissues, including the hyaline cartilage of the epiphyseal growth plate. While apatite crystals appear as unwanted deposits in other cartilage sites, more frequently, crystalline materials other than or in addition to apatite develop in dystrophic cartilage deposits. These crystalline materials include calcium pyrophosphate dihydrate and other calcium phosphate and calcium carbonate phases, monosodium urate, calcium oxalate, cholesterol, and crystallized proteins. This review describes the physical chemistry of crystal deposition and the events that occur in the growth plate as a basis for understanding the pathogenesis of nonphysiologic crystal deposition in cartilage.

Apatites↗
PubMed1983

Presence of link protein in cartilage from cmd/cmd (cartilage matrix deficiency) mice.

Immunohistochemical and biochemical evidence that the cartilage from cmd/cmd mice, who have an autosomal recessive lethal mutation causing cartilage matrix deficiency, synthesizes link protein nearly at a normal level is provided. Since cartilage-characteristic proteoglycan is not synthesized in this mutant mouse (K. Kimata, H-J. Barrach, K. S. Brown, and J. P. Pennypacker (1981) J. Biol. Chem. 256, 6961-6968), link proteins are apparently not in conventional proteoglycan aggregate. However, the link proteins are functional and able to interact with exogenous cartilage-characteristic proteoglycan monomer and hyaluronic acid to form aggregates.

Animals↗
PubMed2005

Lineage plasticity and cell biology of fibrocartilage and hyaline cartilage: its significance in cartilage repair and replacement.

Cartilage repair is a major goal of modern tissue engineering. To produce novel engineered implants requires a knowledge of the basic biology of the tissues that are to be replaced or reproduced. Hyaline articular cartilage and meniscal fibrocartilage are two tissues that have excited attention because of the frequency with which they are damaged. A basic strategy is to re-engineer these tissues ex vivo by stimulating stem cells to differentiate into the cells of the mature tissue capable of producing an intact functional matrix. In this brief review, the sources of cells for tissue engineering cartilage and the culture conditions that have promoted differentiation are discussed within the context of natural cartilage repair. In particular, the role of cell density, cytokines, load, matrices and oxygen tension are discussed.

Biomechanical Phenomena↗
PubMed2004

Biomechanical assessment of tissue retrieved after in vivo cartilage defect repair: tensile modulus of repair tissue and integration with host cartilage.

Failure to restore the mechanical properties of tissue at the repair site and its interface with host cartilage is a common problem in tissue engineering procedures to repair cartilage defects. Quantitative in vitro studies have helped elucidate mechanisms underlying processes leading to functional biomechanical changes. However, biomechanical assessment of tissue retrieved from in vivo studies of cartilage defect repair has been limited to compressive tests. Analysis of integration following in vivo repair has relied on qualitative histological methods. The objectives of this study were to develop a quantitative biomechanical method to assess (1) the tensile modulus of repair tissue and (2) its integration in vivo, as well as determine whether supplementation of transplanted chondrocytes with IGF-I affected these mechanical properties. Osteochondral blocks were obtained from a previous 8 month study on the effects of IGF-I on chondrocyte transplantation in the equine model. Tapered test specimens were prepared from osteochondral blocks containing the repair/native tissue interface and adjacently located blocks of intact native tissue. Specimens were then tested in uniaxial tension. The tensile modulus of repair tissue averaged 0.65 MPa, compared to the average of 5.2 MPa measured in intact control samples. Integration strength averaged 1.2 MPa, nearly half the failure strength of intact cartilage samples, 2.7 MPa. IGF-I treatment had no detectable effects on these mechanical properties. This represents the first quantitative biomechanical investigation of the tensile properties of repair tissue and its integration strength in an in vivo joint defect environment.

Animals↗
PubMed2005

Ovariectomy alters the structural and biomechanical properties of ovine femoro-tibial articular cartilage and increases cartilage iNOS.

OBJECTIVE: To examine the effect of oestrogen depletion produced by surgical ovariectomy on the structural and biomechanical properties of ovine femoro-tibial articular cartilage (AC), and the production of inducible nitric oxide synthase (iNOS) and nitrotyrosine by these tissues. METHODS: Six aged ewes were surgically ovariectomised (OVX), while six were used as unoperated controls. Dynamic biomechanical indentation testing of tibial plateau AC was performed at 26 weeks post-op. Histological sections of medial tibial plateau and lateral tibial plateau (LTP), medial and lateral femoral condyles (MFC, LFC) and patellar AC were examined for histopathology, toluidine blue staining intensity, and patterns of collagen birefringence intensity. Immunoreactivity for iNOS and nitrotyrosine was assessed in full-thickness biopsy plugs of LFC and patellar AC, and patellar AC explants were cultured to determine in vitro NO release. RESULTS: Phase lag was reduced overall in LTP-AC of OVX sheep (10.9+/-2.2 degrees vs 12.1+/-2.3 degrees ; P<0.0001). Cartilage thickness was reduced in the LTP of OVX sheep (P=0.0002), in association with localised changes in dynamic shear modulus. Toluidine blue staining intensity was reduced in the patella, LFC, and MFC. Histological examination revealed greater histopathology scores in the MFC of OVX animals, and altered collagen birefringence intensity plots in the LTP. Immunostaining for iNOS was increased in patella AC (P=0.008), whilst nitrotyrosine immunoreactivity was increased in patella (P=0.03) and LFC (P<0.0001) AC. NO release by patellar AC explants was also elevated. CONCLUSIONS: Oestrogen depletion induced by OVX caused regional thinning of femoro-tibial cartilage, with biomechanical and histological changes suggestive of a disturbance in the content and/or structural organisation of the proteoglycan and collagen macromolecular assembly. The observed up-regulation of cartilage iNOS suggests a possible mechanism for these matrix changes.

Animals↗
PubMed2003

Origin-associated features of chondrocytes in mouse Meckel's cartilage and costal cartilage: an in vitro study.

Using a cell culture method, we histochemically and immunohistochemically investigated whether chondrocytes deriving from different origins, such as Meckel's or costal cartilages, express similar phenotypic characteristics. Chondrocytes isolated enzymatically from Meckel's and costal cartilages of 17-day embryonic mice both actively proliferated and formed cartilage nodules consisting of toluidine blue-positive proteoglycans and type II collagen. Both deposited calcified cartilaginous matrix as revealed by alkaline phosphatase (ALPase) activity and alizarin red staining throughout 3 weeks in culture. Immunostaining for osteopontin (OP), osteocalcin (OC), and osteonectin (ON) revealed that chondrocytes from both cartilages were positive for their proteins, but type I collagen was detected only in cells transforming from Meckel's chondrocytes late in the culture. Electron microscopy demonstrated that although costal and Meckel's chondrocytes had typical chondrocytic features during 2 weeks in culture, Meckel's chondrocytes transformed into osteocytic cells that produced thick, banded type I collagen fibrils. In contrast, costal chondrocytes maintained typical hypertrophic morphology throughout the final stage of culture. The present study suggests that Meckel's chondrocytes derived from neural crest-ectomesenchyme retain osteogenic potential, and differ from costal chondrocytes originating from mesoderm.

Alkaline Phosphatase↗
PubMed2000

The 2.2-kb promoter of cartilage-derived retinoic acid-sensitive protein controls gene expression in cartilage and embryonic mammary buds of transgenic mice.

Cartilage-derived retinoic acid-sensitive protein (CD-RAP) is a secreted protein primarily expressed in chondrocytes. Pathologically, CD-RAP is detected in melanoma, chondrosarcoma and breast cancer. As an approach to define the transcriptional regulatory domains responsible for induction of chondrocyte activity in vivo, we generated transgenic mice harboring various fragments of the mouse CD-RAP promoter linked to the Escherichia coli beta-galactosidase gene. Analysis of the transgene expression pattern by X-gal staining indicates that 2251 bp of the CD-RAP 5'-flanking sequence generates beta-galactosidase activity in all cartilage in embryos and adult animals. In addition, we also detected transient X-gal staining in mammary gland primordium from day 11.5 to 15.5 of gestation. Histological examination revealed that the transgene is located in the chondrocytes of cartilage and the epithelial cells of mammary buds. The cartilage transgene expression pattern is consistent with that of endogenous CD-RAP gene expression. The presence of beta-galactosidase in the mammary buds led us to the demonstration of a unique pattern of transient endogenous expression of CD-RAP in the mammary bud. The finding of transient CD-RAP expression in mammary buds suggests that it may play a role in the organogenesis of mammary glands.

Animals↗