| Summary: | 碩士 === 國防醫學院 === 生物及解剖學研究所 === 98 === Osteoarthritis (OA), the most common degenerative joint disease in the world, is characterized by slowly progression of articular cartilage degradation. Cartilage homeostasis relies on the controlled metabolism of matrix proteins, such as type II collagen and aggrecan, degraded by proteolytic enzymes like matrix metalloproteinase (MMP) and aggrecanase families, and replaced with new proteins, resulting in a balance between degradation and synthesis. Tissue inhibitor of metalloproteinases (TIMP) family is a glycoprotein expressed in the several tissues as a natural inhibitor of the MMPs. With the onset of OA, the balance shifts toward degradation and there is abnormal expression of various factors especially MMP-13, ADAMTS-4, ADAMTS-5, TIMP-1 and TIMP-3. After menopause, the incidence of OA that affects multiple joint increases in women with greater severity, suggesting a chondro-protective effect of female sex hormone. Till now, with limited literature available, histologic analysis of the preventive effects of estrogen-replacement on articular cartilage using different ovariectomized (OVX) animal showed controversial. In addition, trauma accompany with estrogen deficiency postmenopause may possibly attribute to the severity of osteoarthritis. Therefore, the purpose of this study were to investigate the preventive effects of Raloxifene, a kind of selective estrogen receptor modulator (SERM), on ovariectomized and trauma-induced degeneration of articular cartilage using histomorphometric analysis and mRNA expression assay. The mRNA expression of ADAMTS-4 and ADAMTS-5 decreased in Raloxifene group as compared to no Raloxifene treatment group in 4-week experimental groups. The mRNA expression of MMP-13, TIMP-1 and TIMP-3 increased in 8-week experimental groups as compared to the control group. MMP-13 and TIMP-3 in mRNA expression decreased in Raloxifene group as compared to no Raloxifene treatment group. In addition, histologic evidence were noticed less decrease of glycosaminoglycan (GAG) content and less roughness of articular surface in Raloxifene treatment group as compared to no Raloxifene treatment group. In conclusion, Raloxifene may reduce MMP-13, ADAMTS-4 and ADAMTS-5 expression in articular cartilage of ovariectomized and trauma-induced osteoarthritic rabbits and provide main chondro–protective effects during the early stage of osteoarthritis.
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