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.

中文翻译：

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Raloxifene抑制骨质疏松性骨关节炎大鼠软骨中TGF-β1的过表达并调节软骨下骨的代谢。

转化生长因子-β1 (TGF-β1) 的过度表达和软骨下骨重塑在骨关节炎 (OA) 中起关键作用。雷洛昔芬 (RAL) 可降低绝经后妇女的血清 TGF-β1 水平。然而，RAL对关节软骨中TGF-β1表达的影响尚不清楚。因此，我们旨在研究 RAL 对由软骨中 TGF-β1 表达和软骨下骨代谢介导的骨质疏松性 OA 的保护作用。骨质疏松性 OA 是由前交叉韧带横断 (ACLT) 和卵巢切除术 (OVX) 联合引起的。将大鼠分为五组（n=12）：sham、ACLT、OVX、ACLT+OVX 和 RAL 组（ACLT+OVX+RAL，6.25 mg/kg/天，持续 12 周）。通过组织形态学、显微计算机断层扫描 (micro-CT)、免疫组织化学和抗酒石酸酸性磷酸酶 (TRAP) 染色。在 ACLT+OVX 组中检测到严重的软骨退变。ACLT+OVX组的组织形态学评分、TGF-β1水平及其相关分解代谢酶和破骨细胞数量均高于其他组（p<0.05）。此外，结构模型指数 (SMI) 和小梁间距 (Tb.Sp) 降低 (p<0.05)，而骨矿物质密度 (BMD)、骨体积分数 (BV/TV) 和小梁数量 (Tb.N)与 ACLT+OVX 组的相应参数相比，RAL 治疗后增加（p<0.05）。我们的研究结果表明，临床剂量的 RAL 可延缓与抑制软骨中 TGF-β1 过度表达和调节软骨下骨代谢相关的骨质疏松性 OA 的发展。