P177 Crosstalk Between INTERLEUKIN-1 and Sphingolipids: SPHINGOSINE-1-PHOSPHATE Abrogates Nitric Oxide Production and Loss of Glycosaminoglycans in Bovine Chondrocytes (original) (raw)
2006, Osteoarthritis and Cartilage
Purpose: Osteoarthritis is a complicated process comprising osteoclast, osteoblast and chondrocyte pathologies. These include osteoclastic bone resorption, osteoblastic bone formation, chondrocyte hypertrophy and subsequent cartilage degradation. At present, there are no ex vivo models which allow for investigation of the combined metabolism of all the implicated cell types in one single simple ex vivo model. The remodelling in the growth plates may partly resemble the cartilage pathology during OA progression. Therefore we developed a growth plate model in which parameters of the OA pathology involving both bone and cartilage parameters can be investigated. We developed a new ELISA assay and techniques to assess MMP derived cartilage degradation, cartilage formation as well as osteoclastic bone resorption. Methods: Tibiae were dissected from embryonic NMRi mice at day 17 post vaginal plug, as previously described. The experiment was designed with a paired control. One tibia was stimulated with 100nM salmon calcitonin (sCT) and compared to vehicle treatment. The experiment was performed in 4 replicates. The ex vivo tissue was cultured in 0.1% BSA in alpha-MEM for 7 days with refreshment of medium other day. We assessed parameters of tissue turnover in the conditioned medium by an array of ELISA assays 1) bone resorption by CTX-I 2) MMP mediated collagen type II degradation by CTX-II 3) cartilage formation by pro-collagen type II, PIIb. For clarification, conditioned medium was measured at all days, and data are accumulated over the entire culture period. Results: Calcitonin inhibited bone resorption (CTX-I) (P<0.01) by 50%, and collagen type II degradation (CTX-II) by 50%. Collagen type II formation (PIIb) was stimulated by 75% (P<0.01). Conclusions: By combining a novel ex vivo tissue culture with biochemical markers that are specific products of enzyme activity, we have developed a biological model in which most of the parameters in the progression of OA can be investigated. This model system allows for accurate profiling of hormones and other molecules that positively could affect the disease mechanisms of OA and therefore progression of OA. Calcitonin has been suggested to be a possible treatment for OA. Calcitonin inhibited cartilage and bone degradation, and stimulated cartilage formation. Calcitonin affects both osteoclast and chondrocyte metabolism, and seems to shift chondrocyte activity toward a cartilage formation rather than a cartilage degradation phenotype.
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