Mechanosensitive miR-99b mediates the regulatory effect of matrix stiffness on bone marrow mesenchymal stem cell fate both in vitro and in vivo

作者全名："Cao, Bojun; Li, Jiaxin; Wang, Xiaowen; Ran, Zhaoyang; Tan, Jia; Deng, Liang; Hao, Yongqiang"

作者地址："[Cao, Bojun; Ran, Zhaoyang; Tan, Jia; Deng, Liang; Hao, Yongqiang] Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 9, Dept Orthopaed Surg, Shanghai Key Lab Orthopaed Implants,Sch Med, Shanghai 200011, Peoples R China; [Li, Jiaxin] Harbin Med Univ, Dept Orthoped, Affiliated Hosp 2, Harbin, Peoples R China; [Wang, Xiaowen] Chongqing Med Univ, Dept Cardiothorac Surg, Affiliated Hosp 1, Chongqing 400016, Peoples R China; [Deng, Liang; Hao, Yongqiang] Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 9, Clin & Translat Res Ctr 3D Printing Technol, Sch Med, Shanghai 200011, Peoples R China"

通信作者："Hao, YQ (通讯作者)，Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 9, Dept Orthopaed Surg, Shanghai Key Lab Orthopaed Implants,Sch Med, Shanghai 200011, Peoples R China.; Hao, YQ (通讯作者)，Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 9, Clin & Translat Res Ctr 3D Printing Technol, Sch Med, Shanghai 200011, Peoples R China."

来源：APL BIOENGINEERING

ESI学科分类：　

WOS号：WOS:000919289700002

JCR分区：Q1

影响因子：6.6

年份：2023

卷号：7

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："Mechanical signals from extracellular matrix stiffness are important cues that regulate the proliferation and differentiation of bone marrow mesenchymal stem cells (BMSCs). However, the incorporation of BMSCs into soft hydrogels and the dominance of soft matrices for BMSC growth and differentiation limit the directed differentiation of BMSCs incorporated into hydrogels for tissue engineering, especially osteogenesis. Here, we found that the expression of miR-99b increased with increasing hydrogel stiffness and that miR-99b regulated the proliferation and differentiation of BMSCs seeded on the surface of substrates with different stiffnesses. Furthermore, miR-99b significantly promoted the migration of BMSCs in 3D hydrogels. Mechanistically, we demonstrated that matrix stiffness-sensitive miR-99b targets the mammalian target of the rapamycin signaling pathway to regulate the adipogenic and osteogenic differentiation of BMSCs. In addition, by modulating the expression of miR-99b, the osteogenic differentiation of BMSCs in soft 3D hydrogels was promoted. Consistently, the flexible BMSC-GelMA hydrogel transfected with miR-99b significantly promoted bone regeneration in the rat calvarial defect area. These results suggest that miR-99b plays a key role in the mechanotransduction and phenotypic transformation of BMSCs and may inspire new tissue engineering applications with MSCs as key components."

基金机构：General Program of NSFC [81972058]; Shanghai Key Clinical Specialty Construction Project-Biomedical Materials [shslczdzk06701]; Three-year Action Plan of Shenkang Development Center [SHDC2020CR2019B]; Huangpu District Industrial Support Fund [XK2020009]; National Key Science and Technology Infrastructure of Translational Medicine (Shanghai) Open Project [TMSZ-2020-207]; Shanghai Engineering Research Center of Innovative Orthopedic Instruments and Personalized Medicine [19DZ2250200]

基金资助正文："We are grateful for the funding support from the General Program of NSFC (No. 81972058), the Shanghai Key Clinical Specialty Construction Project-Biomedical Materials (No. shslczdzk06701), the Three-year Action Plan of Shenkang Development Center (No. SHDC2020CR2019B), the Huangpu District Industrial Support Fund (No. XK2020009), the National Key Science and Technology Infrastructure of Translational Medicine (Shanghai) Open Project (No. TMSZ-2020-207), and the Shanghai Engineering Research Center of Innovative Orthopedic Instruments and Personalized Medicine (No. 19DZ2250200)."