title: Cyclic compressive stress-induced scinderin regulates progress of developmental dysplasia of the hip.
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.
authors.affiliation: Department of Orthopedic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), China.
authors.forename: Cheng-Long
authors.initials: CL
authors.lastname: Wang
authors.affiliation: Department of Orthopedic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Orthopedic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), China.
authors.forename: Fei
authors.initials: F
authors.lastname: Xiao
authors.affiliation: Department of Orthopedic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), China.
authors.forename: Chuan-Dong
authors.initials: CD
authors.lastname: Wang
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) & Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences, Shanghai, China.
authors.forename: Guo-Li
authors.initials: GL
authors.lastname: Hu
authors.affiliation: Department of Orthopedic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), China.
authors.forename: Jun-Feng
authors.initials: JF
authors.lastname: Zhu
authors.affiliation: Department of Orthopedic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), China.
authors.forename: Chao
authors.initials: C
authors.lastname: Shen
authors.affiliation: Department of Orthopedic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zuo
authors.affiliation: Department of Orthopedic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), China.
authors.forename: Yi-Min
authors.initials: YM
authors.lastname: Cui
authors.affiliation: Department of Orthopedic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), China.
authors.forename: De
authors.lastname: Li
authors.affiliation: Department of Orthopedic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), China.
authors.lastname: Yuan-Gao
authors.affiliation: Department of Orthopedic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), China. Electronic address: xlzhang@sibs.ac.cn.
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Zhang
authors.affiliation: Department of Orthopedic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), China. Electronic address: chenxdmd@163.com.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Chen
mesh_terms: D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism; D020219:Chondrogenesis / Q000235:genetics; D018450:Disease Progression; D018260:Gelsolin / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006618:Hip Dislocation, Congenital / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D020935:MAP Kinase Signaling System; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D008819:Mice, Nude; D016328:NF-kappa B / Q000378:metabolism; D010006:Osteoblasts / Q000378:metabolism; D010012:Osteogenesis / Q000235:genetics; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013314:Stress, Mechanical; D014183:Transplantation, Heterologous
chemical_list: D018260:Gelsolin; D016328:NF-kappa B; C065395:scinderin
keywords: Chondrocyte; Cyclic compressive stress; Developmental dysplasia of the hip; Osteoblast; Scinderin