RRC ID 52102
著者 Wang CL, Wang H, Xiao F, Wang CD, Hu GL, Zhu JF, Shen C, Zuo B, Cui YM, Li D, Yuan-Gao, Zhang XL, Chen XD.
タイトル Cyclic compressive stress-induced scinderin regulates progress of developmental dysplasia of the hip.
ジャーナル Biochem Biophys Res Commun
Abstract 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 the p-Smad1/5/8, NF-κB, and MAPK P38 signaling pathways, as well as stimulated the expression of key osteoclast transcriptional factors NFATc1 and c-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.
巻・号 485(2)
ページ 400-408
公開日 2017-4-1
DOI 10.1016/j.bbrc.2017.02.065
PII S0006-291X(17)30335-2
PMID 28213129
MeSH Animals Blotting, Western Cell Line, Tumor Cells, Cultured Chondrocytes / metabolism Chondrogenesis / genetics Disease Progression Gelsolin / genetics* Gelsolin / metabolism Gene Expression Regulation* Hip Dislocation, Congenital / genetics* Hip Dislocation, Congenital / metabolism Hip Dislocation, Congenital / pathology Humans MAP Kinase Signaling System Mesenchymal Stem Cell Transplantation Mesenchymal Stem Cells / metabolism Mice, Nude NF-kappa B / metabolism Osteoblasts / metabolism Osteogenesis / genetics Rats Reverse Transcriptase Polymerase Chain Reaction Stress, Mechanical* Transplantation, Heterologous
IF 2.985
引用数 6
リソース情報
ヒト・動物細胞 ATDC5(RCB0565)