Short-term Effects of Raloxifene on Articular Cartilage in Ovariectomized and Trauma-induced Osteoarthritic Rabbits

• Main Authors: Pai-shan Hsieh, 謝百善
• Other Authors: Chung Shih
• Format: Others
• Language: zh-TW
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/28173461884070509672

碩士 === 國防醫學院 === 生物及解剖學研究所 === 98 === Osteoarthritis (OA) is characterized by slowly progression of articular cartilage degradation caused by disturbed metabolism of matrix proteins, such as type II collagen and aggrecan. After menopause, the incidence of OA affecting multiple joints increases in women with greater severity, suggesting a chondroprotective effect of female sex hormone, estrogen. Estrogen acts on different tissues and organs through activation of estrogen receptors (ERs), which has been demonstrated in both subtypes (ER and ER) in articular cartilages. After menopause, ERs decreased due to estrogen deficiency, but the relative change of two ER subtypes and its effect on cartilage degradation is still unclear. The purposes of this study were to investigate possible chondroprotective effects and cellular mechanism of raloxifene, a kind of selective estrogen receptor modulator (SERM), using ovariectomized (OVX) and trauma-induced OA animal model. In the experimental rabbits, OVX and trauma surgery were performed and then followed/or not followed by oral administration of raloxifene. The synovial fluid sample from each group was collected for evaluation of C-terminal crosslinking telopeptide of type II collagen (CTX-II) levels by ELISA. The gross morphology and histological observation showed less loss of glycosaminoglycan (GAG) with raloxifene treatment in 8-week groups and less formation of clefts in 2-week groups as compared to no treatment groups. In CTX-II ELISA, four weeks after Raloxifene treatment, significant lower CTX-II expression was noted as compared to no treatment groups. Also, raloxifene treatment in 4- and 8-week groups resulted in significant decrease in CTX-II as compared to 1- and 2-week groups. Therefore, raloxifene may have chondroprotective effects in early stage OA, and the chondroprotective effects are more evident as the disease continuously progresses.