Raloxifene inhibits the overexpression of TGF-β1 in cartilage and regulates the metabolism of subchondral bone in rats with osteoporotic osteoarthritis
Overexpression of transforming growth factor-beta 1 (TGF-β1) and subchondral bone remodeling play key roles in osteoarthritis (OA). Raloxifene (RAL) reduces the serum level of TGF-β1 in postmenopausal women. However, the effect of RAL on TGF-β1 expression in articular cartilage remains unclear. Therefore, we aimed to investigate the protective effect of RAL against osteoporotic OA mediated by TGF-β1 expression in the cartilage and the metabolism of subchondral bone. Osteoporotic OA was induced by a combination of anterior cruciate ligament transection (ACLT) and ovariectomy (OVX). Rats were divided into five groups (n=12): the sham, ACLT, OVX, ACLT+OVX and RAL groups (ACLT+OVX+RAL, 6.25 mg/kg/day for 12 weeks). Assessment was performed by histomorphology, microcomputed tomography (micro-CT), immunohistochemistry and tartrate-resistant acid phosphatase (TRAP) staining. Extreme cartilage degeneration was detected in the ACLT+OVX group. The histomorphological scores, levels of TGF-β1 and its related catabolic enzymes and osteoclasts numbers in the ACLT+OVX group were higher than those in other groups (p<0.05). Furthermore, the structure model index (SMI) and trabecular spacing (Tb.Sp) were decreased (p<0.05), while the bone mineral density (BMD), bone volume fraction (BV/TV) and trabecular number (Tb.N) were increased after treatment with RAL compared with the corresponding parameters in the ACLT+OVX group (p<0.05). Our findings demonstrated that RAL at clinical doses retards the development of osteoporotic OA associated with the inhibition of TGF-β1 overexpression in the cartilage and regulation of subchondral bone metabolism. These results suggest an expansion of the clinical indications for RAL to include the prevention and treatment of postmenopausal OA.
Copyright (c) 2020 Shao-Hua Ping, Fa-Ming Tian, Hao Liu , Qi Sun, Li-Tao Shao, Qiang-Qiang Lian, Liu Zhang
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