Matricellular Protein SMOC2 Potentiates BMP9-Induced Osteogenic Differentiation in Mesenchymal Stem Cells through the Enhancement of FAK/PI3K/AKT Signaling

作者全名："He, Wen-Ge; Deng, Yi-Xuan; Ke, Kai-Xin; Cao, Xuan-Lin; Liu, Si-Yuan; Yang, Yuan-Yuan; Luo, Hong-Hong; Yao, Xin-Tong; Gao, Xiang; Du, Yu; He, Bai-cheng; Chen, Liang"

作者地址："[He, Wen-Ge; Cao, Xuan-Lin; Liu, Si-Yuan; Chen, Liang] Chongqing Univ Canc Hosp, Dept Bone & Soft Tissue Oncol, Chongqing 400030, Peoples R China; [He, Wen-Ge; Cao, Xuan-Lin; Liu, Si-Yuan; Gao, Xiang; Du, Yu; Chen, Liang] Chongqing Med Univ, Affiliated Hosp 2, Dept Orthoped, Chongqing 400010, Peoples R China; [He, Wen-Ge; Deng, Yi-Xuan; Ke, Kai-Xin; Cao, Xuan-Lin; Liu, Si-Yuan; He, Bai-cheng] Chongqing Med Univ, Key Lab Biochem & Mol Pharmacol Chongqing, Chongqing 400016, Peoples R China; [Deng, Yi-Xuan; Ke, Kai-Xin; Yang, Yuan-Yuan; Luo, Hong-Hong; Yao, Xin-Tong; He, Bai-cheng] Chongqing Med Univ, Sch Pharm, Dept Pharmacol, Chongqing 400016, Peoples R China"

通信作者："Chen, L (通讯作者)，Chongqing Univ Canc Hosp, Dept Bone & Soft Tissue Oncol, Chongqing 400030, Peoples R China.; Chen, L (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Orthoped, Chongqing 400010, Peoples R China."

来源：STEM CELLS INTERNATIONAL

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000921293500001

JCR分区：Q2

影响因子：3.8

年份：2023

卷号：2023

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："Mesenchymal stem cells (MSCs) can self-renew and differentiate into multiple lineages, making MSC transplantation a promising option for bone regeneration. Both matricellular proteins and growth factors play an important role in regulating stem cell fate. In this study, we investigated the effects of matricellular protein SMOC2 (secreted modular calcium-binding protein 2) on bone morphogenetic protein 9 (BMP9) in mouse embryonic fibroblasts (MEFs) and revealed a possible molecular mechanism underlying this process. We found that SMOC2 was detectable in MEFs and that exogenous SMOC2 expression potentiated BMP9-induced osteogenic markers, matrix mineralization, and ectopic bone formation, whereas SMOC2 knockdown inhibited these effects. BMP9 increased the levels of p-FAK and p-AKT, which were either enhanced or reduced by SMOC2 and FAK silencing, respectively. BMP9-induced osteogenic markers were increased by SMOC2, and this increase was partially abolished by silencing FAK or LY290042. Furthermore, we found that general transcription factor 2I (GTF2I) was enriched at the promoter region of SMOC2 and that integrin beta 1 interacted with SMOC2 in BMP9-treated MEFs. Our findings demonstrate that SMOC2 can promote BMP9-induced osteogenic differentiation by enhancing the FAK/PI3K/AKT pathway, which may be triggered by facilitating the interaction between SMOC2 and integrin beta 1."

基金机构："National Natural Science Foundation of China [82000836]; Youth Science Fund Project, Chongqing Natural Science Foundation [Nos.2022NSCQ-MSX1032]; Chongqing Medical Association Scientific Research and Seedling Cultivation Project [cmba2022kyym-zkxM0006]"

基金资助正文："This work was supported by the National Natural Science Foundation of China (Grant Nos.82000836) The Youth Science Fund Project, Chongqing Natural Science Foundation (Grant Nos.2022NSCQ-MSX1032), and the Chongqing Medical Association Scientific Research and Seedling Cultivation Project (Grant Nos.cmba2022kyym-zkxM0006)."