Zhou Yan, Ming Jianghua, Li Yaming, Du Xianjin, Deng Ming, He Bin, Zhou Jianlin, Wang Guirong, Liu Shiqing
Department of Orthopedics, Central Laboratory, Renmin Hospital of Wuhan University, Wuhan 430060, China.
Department of Surgery, SUNY Upstate Medical University, Syracuse, NY 13210, USA.
Biochem Biophys Res Commun. 2018 Jan 1;495(1):526-532. doi: 10.1016/j.bbrc.2017.10.170. Epub 2017 Oct 31.
Innate immune molecule surfactant protein D (SP-D), a member of the C-type lectin protein family, plays an indispensable role in host defense and the regulation of inflammation in the lung and other tissues. Osteoarthritis (OA) is a degenerative disease of cartilage, with inflammation that causes pathologic changes and tissue damage. However, it is unknown whether there exist SP-D expression and its potential role in the pathogenesis of OA. In this study, we examined SP-D expression and explored its biological function in a sodium nitroprusside (SNP)-stimulated rat chondrocytes and surgically-induced rat OA model. We found SP-D expression in both human and rat articular chondrocytes, with higher level in normal chondrocytes compared to in OA chondrocytes. Furthermore, In vivo study demonstrated that recombinant human SP-D (rhSP-D) ameliorated cartilage degeneration in surgically-induced rat OA model. In vitro cell culture study showed that rhSP-D markedly inhibited the expression of caspase-3 as an apoptosis biomarker, and decreased phosphorylation of p38 mitogen-activated protein kinase (MAPK), which resulted in maintaining normal nuclear morphology and increasing mitochondrial membrane potential in SNP-stimulated rat chondrocytes. Collectively, these findings indicate that SP-D expresses in articular chondrocytes and suppresses SNP-stimulated chondrocyte apoptosis and ameliorates cartilage degeneration via suppressing p38 MAPK activity.
天然免疫分子表面活性蛋白D(SP-D)是C型凝集素蛋白家族的成员,在宿主防御以及肺和其他组织的炎症调节中发挥着不可或缺的作用。骨关节炎(OA)是一种软骨退行性疾病,其炎症会导致病理变化和组织损伤。然而,尚不清楚OA发病机制中是否存在SP-D表达及其潜在作用。在本研究中,我们检测了SP-D的表达,并在硝普钠(SNP)刺激的大鼠软骨细胞和手术诱导的大鼠OA模型中探究了其生物学功能。我们发现人和大鼠关节软骨细胞中均有SP-D表达,与OA软骨细胞相比,正常软骨细胞中的表达水平更高。此外,体内研究表明重组人SP-D(rhSP-D)改善了手术诱导的大鼠OA模型中的软骨退变。体外细胞培养研究表明,rhSP-D显著抑制了作为凋亡生物标志物的半胱天冬酶-3的表达,并降低了p38丝裂原活化蛋白激酶(MAPK)的磷酸化,这导致在SNP刺激的大鼠软骨细胞中维持正常的核形态并增加线粒体膜电位。总的来说,这些发现表明SP-D在关节软骨细胞中表达,并通过抑制p38 MAPK活性抑制SNP刺激的软骨细胞凋亡并改善软骨退变。