| Summary: | 碩士 === 高雄醫學大學 === 生理及分子醫學研究所 === 97 === Osteoarthritis (OA) is a degenerative joint disease and associated with changes in glycosaminoglycan (GAG) and collagen levels, but the mechanism remains to be defined. During OA progression, articular chondrocytes undergo terminal differentiation as that occurs during endochondral ossification. Previous studies showed that parathyroid hormone-related peptide (PTHrP) can suppress terminal differentiation of chondrocytes during endochondral ossification. Our previous finding emphasized that PTH (1-34) can suppress the progress of terminal differentiation in cultured human articular chondrocytes (HACs) and papain-induced OA in rats. PTH and PTHrP share the same receptor PTHR1, and subsequently stimulates both adenylate cyclase (PKA pathway) and phospholipase-C (PKC pathway). Previous reports showed that PTH (1-31) had high affinity to bind to PTHR1 and stimulated adenylate cyclase but not phospholipase-C. Therefore, in this study we hypothesized that PTH (1-31) suppress terminal differentiation of articular chondrocytes through cAMP/PKA signaling, and thus suppress OA progression. OA was induced by intra-articular injections of papain solution and cystein in the right knees of rats and left knee of each rat was as the contralateral control. The rats were divided into five groups: OA, PTH (1-34), PTH (1-31), OA+PTH (1-34), and OA+PTH (1-31). Our data showed that the PTH (1-31) treatment suppressed the papain-induced OA changes. The Safranin-O-Fast-Green staining showed that GAG level reduced in OA group, but not in the OA+ PTH (1-34) and the OA+PTH (1-31) groups. The immunohistochemistry analysis indicated that the level of COL II showed a marked increase in the OA+ PTH (1-34) and the OA+ PTH (1-31) groups; the COL X expression was less in the OA+ PTH (1-34) and the OA+ PTH (1-31) groups compared with the OA group. The level of GAG, COL II and COL X of the contralateral control cartilage were not significantly different among the five groups. In the present study, we found that PTH (1-31) and PTH (1-34) showed the similar effect on suppressing GAG loss in the papain-induced OA rat model. And, we further found that PTH (1-31) significantly suppressed the COL X expression and chondrocytes apoptosis than PTH (1-34). But, PTH (1-34) was more effective than PTH (1-31) on maintaining the COL II content in OA rats. On the other hand, PTH (1-31) did not affect the intact articular cartilage. According to the results, we suggest that the suppressive effect of PTH (1-31) on COL X expression and apoptosis in articular chondrocytes might due to cAMP/ PKA signaling pathway, but not PKC signaling pathway which may contribute to maintaining chondrocyte differentiation.
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