Salubrinal通过调节破骨细胞发育改善骨关节炎 胫骨平台不均匀沉降

摘要：目的 观察Salubrinal对早期骨关节炎（OA）小鼠胫骨平台不均匀沉降的治疗作用。方法 30只小鼠随机 分为对照（Sham）组、OA组和OA+Salubrinal（OA+Sal）组。采用手术切除小鼠膝关节内侧半月板建立OA模型，Sham 组只切开关节内侧皮肤；OA+Sal组小鼠皮下注射Salubrinal （1 mg/kg）2周，Sham组及OA组给予等量的生理盐水。采 用番红O和抗酒石酸酸性磷酸酶（TRAP）染色，观察胫骨平台内侧和外侧的组织形态学改变以及破骨细胞活性变化。 使用骨髓细胞的破骨细胞形成、迁移、黏附实验检测破骨细胞发育情况。结果 与Sham组相比，OA组破骨细胞发育 显著激活，软骨下骨的破骨细胞活性也明显增高；关节软骨OARSI评分、钙化软骨比例（CC/TAC）均显著升高（P＜ 0.05）；胫骨平台内侧软骨下骨的骨面积分数（B.Ar/T.Ar）明显增加（P＜0.05），但外侧B.Ar/T.Ar、软骨下骨板（SBP）厚 度均显著降低（P＜0.05）。与OA组相比，OA+Sal组破骨细胞发育及软骨下骨破骨细胞活性被抑制，OARSI评分、CC/ TAC 均有所降低（P＜0.05）；而且，内外侧胫骨平台软骨下骨 B.Ar/T.Ar 和 SBP 厚度的不均匀改变均明显恢复（P＜ 0.05）。结论 Salubrinal通过调控破骨细胞发育对早期OA胫骨平台的骨重建和不均匀沉降有明显的改善作用。

Salubrinal improves the non-uniform settlement of tibial plateau in osteoarthritis through regulating osteoclast development

Abstract: Objective To observe the therapeutic effect of Salubrinal on non-uniform settlement of tibial plateau in early osteoarthritis of surgery-induced mouse model. Methods Thirty mice were randomly equally divided into sham operation group (Sham), osteoarthritis group (OA) and osteoarthritis + Salubrinal group (OA + Sal). The OA model was established using surgery-removed medial meniscus of the knee joint in mice. Mice of OA + Sal group were injected subcutaneously with Salubrinal (1 mg/kg) for two weeks, Sham group and OA group were treated with isodose normal saline. Safranin O and tartrate-resistant acid phosphatase (TRAP) staining were used to observe the changes of histomorphology and the osteoclast activity in medial and lateral tibia plateau. The ability of formation, migration and adhension of osteoclasts from bone marrow-derived cells were evaluated to detect the development of osteoclasts. Results Compared with Sham group, the osteoclast development was significantly activated in OA group, and the osteoclast activity of subchondral bone was also increased. The OARSI score of articular cartilage and the proportion of calcified cartilage (CC/TAC) were obviously elevated (P＜0.05) in OA group. Interestingly, the medial tibial plateau B.Ar/T.Ar was increased significantly (P＜0.05), but the B.Ar/T.Ar and SBP were decreased significantly at lateral tibial plateau (P＜0.05) in OA group. Compared with OA group, the osteoclast development and subchondral osteoclast activity were significantly inhibited in OA + Sal group (P＜ 0.05). The OARSI score and CC/TAC were decreased (P＜0.05) in OA+Sal group. Moreover, the non-uniform changes of B. Ar / T. Ar and SBP were recovered apparently in the subchondral bone of the medial and lateral tibial plateau (P＜0.05). Conclusion Salubrinal plays a significant role in bone remodeling and non-uniform settlement of tibial plateau at early stage of osteoarthritis through regulating osteoclast development.