Cyclic compressive stress-induced scinderin regulates progress of developmental dysplasia of the hip
Cyclic compressive stress-induced scinderin regulates progress of developmental dysplasia of the hip
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循环压缩应力诱导的 scinderin 调节髋关节发育不良的进展
DOI：
10.1016/j.bbrc.2017.02.065
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发表时间：
2017
影响因子：
3.1
通讯作者：
Chen Xiao-Dong
中科院分区：
文献类型：
--
作者：
Wang Cheng-Long;Wang Hui;Xiao Fei;Wang Chuan-Dong;Hu Guo-Li;Zhu Jun-Feng;Shen Chao;Zuo Bin;Cui Yi-Min;Li De;Yuan-Gao;Zhang Xiao-Ling;Chen Xiao-Dong
发育性髋关节发育不良(DDH)是一种常见的肌肉骨骼疾病，其特征是髋臼和股骨头不匹配。在髋臼、股骨头畸形的发生发展过程中，机械力起着重要作用。在本研究中，我们建立了一种名为循环压应力(CCS)的力学模型。为了分析CCS对DDH的影响，我们检测了软骨细胞和成骨细胞中的特异基因。结果表明，CCS以浓度依赖的方式抑制ADTC5的软骨生成。此外，Scinderin(SCIN)的信使核糖核酸水平显著升高。我们建立了慢病毒-SCIN(GV144-SCIN)载体，以不同CCS水平(0.25、0.5、1、10)处理hBMSCs，结果表明，SCIN过表达可促进成骨和破骨细胞的生成。相比之下，包括Acan、Col-2A和Sox9在内的软骨细胞特异性基因的表达减少。进一步的分子研究表明，SCIN通过激活p-Smad1/5/8、NF-κB和MAPKP38信号通路促进成骨和破骨细胞生成，并刺激关键破骨细胞转录因子NFATc1和c-Fos的表达。此外，在体内，SCIN诱导的成骨作用超过了在缺损性股骨中的破骨作用。Micro-CT的分析结果证实了上述发现。总体而言，CCS通过促进成骨和软骨降解而影响DDH的发展。此外，SCIN在DDH的发展中发挥了至关重要的作用。
Developmental dysplasia of the hip (DDH) is a common musculoskeletal disorder characterized by a mismatch between acetabulum and femoral head. Mechanical force plays an important role during the occurrence and development of abnormities in acetabulum and femoral head. In this study, we established a mechanical force model named cyclic compressive stress (Ccs). To analyze the effect of Ccs on DDH, we detected special genes in chondrocytes and osteoblasts. Results showed that Ccs downregulated chondrogenesis of ADTC5 in a concentration-dependent manner. Moreover, the mRNA level of Scinderin (Scin) considerably increased. We established lentivirus-SCIN(GV144-SCIN) to transfect hBMSCs, which were treated with different Ccs levels (0.25 Hz*5 cm, 0.5 Hz*5 cm, and 1 Hz*10 cm); the result showed that overexpression of Scin upregulated osteogenesis and osteoclastogenesis. By contrast, expression of chondrocyte-specific genes, including ACAN, COL-2A, and Sox9, decreased. Further molecular investigation demonstrated that Scin promoted osteogenesis and osteoclastogenesis through activation of thep-Smad1/5/8, NF-κB, and MAPK P38 signaling pathways, as well as stimulated the expression of key osteoclast transcriptional factors NFATc1 andc-Fos. Moreover, Scin-induced osteogenesis outweighed osteoclastogenesis in defective femur in vivo. The results of the analysis of Micro-CT confirmed these findings.Overall, Ccs influenced the development of DDH by promoting osteogenesis and cartilage degradation. In addition, Scin played a vital role in the development of DDH.