Raloxifene inhibits the overexpression of TGF-β1 in cartilage and regulates the metabolism of subchondral bone in rats with osteoporotic osteoarthritis

Keywords: Osteoporosis, osteoarthritis, raloxifene, TGF-β1, cartilage, subchondral bone

Abstract

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.

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Raloxifene inhibits the overexpression of TGF-β1 in cartilage and regulates the metabolism of subchondral bone in rats with osteoporotic osteoarthritis
Published
2020-11-19
How to Cite
1.
PingS-H, TianF-M, Liu H, Sun Q, ShaoL-T, LianQ-Q, Zhang L. Raloxifene inhibits the overexpression of TGF-β1 in cartilage and regulates the metabolism of subchondral bone in rats with osteoporotic osteoarthritis. Bosn J of Basic Med Sci [Internet]. 2020Nov.19 [cited 2020Dec.1];. Available from: https://www.bjbms.org/ojs/index.php/bjbms/article/view/5142
Section
Pathology

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