Zhang Lai-Bo, Man Zhen-Tao, Li Wei, Zhang Wei, Wang Xian-Quan, Sun Shui
Department of Bone and Joint, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
Department of Bone and Joint, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
Mol Immunol. 2017 Jul;87:249-257. doi: 10.1016/j.molimm.2017.05.002. Epub 2017 May 14.
Calcitonin (CT) is an anti-absorbent, which has long been used for treatment of osteoporosis. However, little information is available about the effects of CT on osteoarthritis (OA). This study was mainly aimed to explore the effects of CT on the treatment of OA, as well as the underlying mechanisms. Chondrocytes were isolated from immature mice and then were incubated with lipopolysaccharide (LPS), CT, small interfering (si) RNA against bone morphogenetic protein (BMP)-2, and/or the inhibitors of MAPK/Wnt/NF-κB pathway. Thereafter, cell viability, apoptosis, nitric oxide (NO) and inflammatory factors productions, and expression levels of cartilage synthesis protein key factors, cartilage-derived morphogenetic protein (CDMP) 1, SRY (sex-determining region Y)-box 9 protein (SOX9), and MAPK/Wnt/NF-κB pathways key factors were determined. CT significantly reversed LPS-induced cell viability decrease, apoptosis increase, the inflammatory factors and NO secretion, the abnormally expression of cartilage synthesis proteins and the activation of MAPK/Wnt/NF-κB pathways (P<0.05). In addition, we observed that administration of the inhibitors of MAPK/Wnt/NF-κB pathways statistically further increased the levels of CDMP1 and SOX9 (P<0.05). Suppression of BMP-2 decreased the levels of CDMP1 and SOX9 and activated MAPK/Wnt/NF-κB pathways, and could partially abolish CT-modulated the expression changes in CDMP1 and SOX9, and MAPK/Wnt/NF-κB pathways key factors (P<0.05). The results showed that CT protects chondrocytes from LPS-induced apoptosis and inflammatory response by regulating BMP-2 and thus blocking MAPK/Wnt/NF-κB pathways.
降钙素（CT）是一种抗吸收剂，长期以来一直用于治疗骨质疏松症。然而，关于CT对骨关节炎（OA）影响的信息却很少。本研究主要旨在探讨CT对OA的治疗作用及其潜在机制。从幼年小鼠中分离软骨细胞，然后用脂多糖（LPS）、CT、针对骨形态发生蛋白（BMP）-2的小干扰（si）RNA和/或MAPK/Wnt/NF-κB通路抑制剂进行孵育。此后，测定细胞活力、凋亡、一氧化氮（NO）和炎症因子产生，以及软骨合成蛋白关键因子、软骨衍生形态发生蛋白（CDMP）1、SRY（性别决定区Y）-盒9蛋白（SOX9）的表达水平，以及MAPK/Wnt/NF-κB通路关键因子。CT显著逆转了LPS诱导的细胞活力下降、凋亡增加、炎症因子和NO分泌、软骨合成蛋白的异常表达以及MAPK/Wnt/NF-κB通路的激活（P<0.05）。此外，我们观察到给予MAPK/Wnt/NF-κB通路抑制剂在统计学上进一步增加了CDMP1和SOX9的水平（P<0.05）。抑制BMP-2降低了CDMP1和SOX9的水平并激活了MAPK/Wnt/NF-κB通路，并且可以部分消除CT调节的CDMP1和SOX9以及MAPK/Wnt/NF-κB通路关键因子的表达变化（P<0.05）。结果表明，CT通过调节BMP-2从而阻断MAPK/Wnt/NF-κB通路来保护软骨细胞免受LPS诱导的凋亡和炎症反应。
