天津医药

天津医药 ›› 2018, Vol. 46 ›› Issue (4): 356-362.doi: 10.11958/20180222

• 实验研究 • 上一篇    下一篇

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

高哲 1，李心乐 1，2，李杰 1，2，张平 1，2△   

  1. 基金项目：国家自然科学基金资助项目（81572100，81772405，81601863），天津滨海新区卫生计生委科技项目（2016BWKY009， 2016BWKY015） 作者单位：1天津医科大学基础医学院人体解剖与组织胚胎学系（邮编300070）；2中国医学科学院，北京协和医学院泰达国际心血管病医 院天津泰达普华医院 作者简介：高哲（1989），女，硕士在读，主要从事骨关节炎的机制研究 △通讯作者 E-mail: pizhang2008@163.com
  • 收稿日期:2018-02-08 修回日期:2018-02-11 出版日期:2018-04-15 发布日期:2018-04-15
  • 通讯作者: 高哲 E-mail:GloriaZZG@163.com
  • 基金资助:
    Salubrinal通过调节内质网应激治疗骨质疏松的机制研究;脊柱机械加载调控血管生成和骨重建治疗骨质疏松的机制研究;机械加载通过调控骨重建和内质网应激治疗骨关节炎的机制研究;机械加载治疗骨关节炎的机制研究;抑制内质网应激治疗激素性股骨头坏死实验研究

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

GAO Zhe1, LI Xin-le1,2, LI Jie1,2, ZHANG Ping1,2△   

  1. 1 Department of Anatomy and Histology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China; 2 Tianjin TEDA Puhua Hospital, TEDA International Cardiovascular Hospital, Chinese Academy of Medical Sciences& Peking Union Medical College △Corresponding Author E-mail: pizhang2008@163.com
  • Received:2018-02-08 Revised:2018-02-11 Published:2018-04-15 Online:2018-04-15
  • Contact: zhe GAO E-mail:GloriaZZG@163.com

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摘要： 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。

关键词: 骨关节炎, 软骨下骨, 骨重建, 破骨细胞, 不均匀沉降, Salubrinal

Abstract: 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.

Key words: osteoarthritis, subchondral bone, bone remodeling, osteoclast, non-uniform settlement, Salubrinal