17 research outputs found
131 SUPPRESSION OF MMP ACTIVITY IN BOVINE CARTILAGE EXPLANTS CULTURES HAS LITTLE IF ANY EFFECT ON THE RELEASE OF AGGRECAN FRAGMENTS CARRYING AGGRECANASE-DERIVED NEO-EPITOPES, WHEREAS CORRESPONDING MMP-DERIVED AGGRECAN AND COLLAGEN FRAGMENTS ARE COMPLETELY ABOLISHED FROM THE SUPERNATANT
P100 INTERLEUKIN-1 ALPHA OR ONCOSTATIN M AND TUMOUR NECROSIS FACTOR ALPHA IN COMBINATION STIMULATE AGGRECANASE BUT NOT MATRIX METALLO PROTEINASE MEDIATED AGGRECAN TURNOVER IN HUMAN ARTICULAR CARTILAGE
215 HUMAN OSTEOARTHRITIS CHONDROCYTES EXPRESS THE CALCITONIN RECEPTOR T. Segovia-Silvestre
P86 ESTROGEN DEFICIENCY RESULTS IN INCREASED TYPE II COLLAGEN DEGRADATION AND DECREASED SYNTHESIS, WHICH LEAD TO INCREASED CARTILAGE EROSION
203 DIFFERENT OF AREAS OF THE HUMAN OSTEOARTHRITIC KNEE CARTILAGE RESPOND DIFFERENTLY TO CATABOLIC AND ANABOLIC STIMULATION WHEN CULTURED
193 HUMAN OSTEOARTHRITIS CHONDROCYTES EXPRESS AND RESPOND TO THE PARATHYROID HORMONE RECEPTOR 1
Erratum to “MMP and non-MMP-mediated release of aggrecan and its fragments from articular cartilage: a comparative study of three different aggrecan and glycosaminoglycan assays” [Osteoarthritis Cartilage 15 (2007) 212–21]
131 SUPPRESSION OF MMP ACTIVITY IN BOVINE CARTILAGE EXPLANTS CULTURES HAS LITTLE IF ANY EFFECT ON THE RELEASE OF AGGRECAN FRAGMENTS CARRYING AGGRECANASE-DERIVED NEO-EPITOPES, WHEREAS CORRESPONDING MMP-DERIVED AGGRECAN AND COLLAGEN FRAGMENTS ARE COMPLETELY ABOLISHED FROM THE SUPERNATANT
Relative contribution of matrix metalloprotease and cysteine protease activities to cytokine-stimulated articular cartilage degradation
SummaryObjectiveBoth matrix metalloprotease (MMP) activity and cathepsin K (CK) activity have been implicated in cartilage turnover. We investigated the relative contribution of MMP activity and CK activity in cartilage degradation using ex vivo and in vivo models.MethodsBovine articular cartilage explants were stimulated with oncostatin M (OSM) 10ng/ml and tumor necrosis factor-α (TNF-α) 20ng/ml in the presence or absence of the broad-spectrum MMP inhibitor GM6001 and the cysteine protease inhibitor, E64. Cartilage degradation was evaluated in the conditioned medium by glycosaminoglycans (GAG), hydroxyproline, and cross-linked C-telopeptide fragments of type II collagen (CTX-II), which were compared to immunohistochemical evaluations of proteoglycans and CTX-II. We assessed MMP expression by gelatine zymography and CK expression by immunohistochemistry. In vivo, CTX-II release was measured from CK-deficient mice.ResultsOSM and TNF-α combined induced significant (P<0.01) increase in cartilage degradation products measured by hydroxyproline and CTX-II compared to vehicle control. The cytokines potently induced MMP expression, assessed by zymography, and CK expression investigated by immunohistochemistry. Inhibition of MMP activity completely abrogated hydroxyproline and CTX-II release (P<0.01) and GAG release (P<0.05). In contrast, E64 resulted in increased CTX-II release by 100% (P<0.05) and inhibited GAG release by 30%. Up-regulation of CTX-II fragments was confirmed in vivo in CK null mice.ConclusionInhibition of MMP activity reduced both proteoglycan loss and type II collagen degradation. In contrast, inhibition of cysteine proteases resulted in an increase rather than a decrease in MMP derived fragments of collagen type II degradation, CTX-II, suggesting altered collagen metabolism
Mice over-expressing salmon calcitonin have strongly attenuated osteoarthritic histopathological changes after destabilization of the medial meniscus
SummaryObjectiveCalcitonin is well-known for its inhibitory actions on bone-resorbing osteoclasts and recently potential beneficial effects on cartilage were shown. We investigated effects of salmon calcitonin (sCT) on the articular cartilage and bone, after destabilization of the medial meniscus (DMM) in normal and sCT over-expressing mice.DesignBone phenotype of transgenic (TG) C57Bl/6 mice over-expressing sCT at 6months and 12months was investigated by (1) serum osteocalcin and urinary deoxypyridinoline and (2) dynamic and normal histomorphometry of vertebrae bodies. In subsequent evaluation of cartilage and subchondral bone changes, 44 10-week old TG or wild-type (WT) mice were randomized into four groups and subjected to DMM or sham-operations. After 7weeks animals were sacrificed, and knee joints were isolated for histological analysis.ResultsTrabecular bone volume (BV/TV) increased 150% after 6months and 300% after 12months in sCT-expressing mice when compared to WT controls (P<0.05). Osteoblast number, bone formation rate and osteocalcin measurements were not affected in TG mice over-expressing sCT. In WT animals, a 5-fold increase in the quantitative erosion index was observed after DMM, and the semi-quantitative OARSI score showed over 400% (P<0.001) increase, compared to sham-operated WT mice. DMM-operated TG mice were protected against cartilage erosion and showed a 65% and 64% (P<0.001) reduction, respectively, for the two histopathological evaluation methods.ConclusionssCT over-expressing mice had higher bone volume, and were protected against cartilage erosion. These data suggest that increased levels of sCT may hamper the pathogenesis of osteoarthritis (OA). However more studies are necessary to confirm these preliminary results