Physiological exercise loading suppresses post-traumatic osteoarthritis progression via an increase in bone morphogenetic proteins expression in an experimental rat knee model
Physiological exercise loading suppresses post-traumatic osteoarthritis progression via an increase in bone morphogenetic proteins expression in an experimental rat knee model
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DOI：
10.1016/j.joca.2016.12.008
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发表时间：
2017-06-01
影响因子：
7
通讯作者：
Kuroki, H.
中科院分区：
文献类型：
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作者：
Iijima, H.;Ito, A.;Kuroki, H.
目的：探讨膝关节创伤后骨性关节炎(PTOA)患者软骨-软骨下骨(SB)单位运动负荷的量效关系。设计：12周龄雄性Wistar大鼠右膝关节行内侧半月板失稳(DMM)手术，对侧膝关节进行假手术。术后4周，分别进行中等强度(12m/min)或大强度(21m/min)的跑台运动，每天30min，每周5天，共4周。术后8周采用组织学和免疫组织化学分析、显微计算机断层扫描(Micro-CT)分析和生物力学测试等方法检测关节软骨和SB的PTOA发育情况。结果：适度运动增加了浅层软骨细胞BMP-2、BMP-4、BMP-6、BMP受体2、pSmad-5和DNA结合蛋白-1抑制因子的表达，抑制了软骨退变、骨赘生长、SB损伤和破骨细胞介导的SB吸收。然而，大强度运动对BMP的表达几乎没有影响，甚至导致这些骨关节炎(OA)变化的进展。适度运动后注射gremlin-1可使膝关节PTOA发展到非运动膝关节的水平。结论：运动对DMM手术膝关节软骨-SB PTOA的发育具有剂量依赖性调节作用。我们的发现揭示了浅层软骨细胞中BMP的表达在抑制生理运动负荷后PTOA发展中的重要作用。有必要进行进一步的研究，以支持骨形态发生蛋白有助于预防PTOA进展的机制。(C)2016国际骨性关节炎研究会。爱思唯尔有限公司出版。保留所有权利。
Objective: To evaluate the dose-response relationship of exercise loading in the cartilage-subchondral bone (SB) unit in surgically-induced post-traumatic osteoarthritis (PTOA) of the knee.Design: Destabilized medial meniscus (DMM) surgery was performed on the right knee of 12-weekold male Wistar rats, and sham surgery was performed on the contralateral knee. Four weeks after the surgery, the animals were subjected to moderate (12 m/min) or intense (21 m/min) treadmill exercises for 30 min/day, 5 days/week for 4 weeks. PTOA development in articular cartilage and SB was examined using histological and immunohistochemical analyses, micro-computed tomography (micro-CT) analysis, and biomechanical testing at 8 weeks after surgery. Gremlin-1 was injected to determine the role of bone morphogenetic protein (BMP) signaling on PTOA development following moderate exercise.Results: Moderate exercise increased BMP-2, BMP-4, BMP-6, BMP receptor 2, pSmad-5, and inhibitor of DNA binding protein-1 expression in the superficial zone chondrocytes and suppressed cartilage degeneration, osteophyte growth, SB damage, and osteoclast-mediated SB resorption. However, intense exercise had little effect on BMP expression and even caused progression of these osteoarthritis (OA) changes. Gremlin-1 injection following moderate exercise caused progression of the PTOA development down to the level of the non-exercise DMM-operated knee.Conclusions: Exercise regulated cartilage-SB PTOA development in DMM-operated knees in a dosedependent manner. Our findings shed light on the important role of BMP expression in superficial zone chondrocytes in attenuation of PTOA development following physiological exercise loading. Further studies to support a mechanism by which BMPs would be beneficial in preventing PTOA progression are warranted. (C) 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.