Open AccessThe miR‐193a‐3p‐MAP3k3 Signaling Axis Regulates Substrate Topography‐Induced Osteogenesis of Bone Marrow Stem Cells
Author(s) -
Lv Yan,
Huang Ying,
Xu Mingming,
Heng Boon Chin,
Yang Congchong,
Cao Cen,
Hu Zhewen,
Liu Wenwen,
Chi Xiaopei,
Gao Min,
Zhang Xuehui,
Wei Yan,
Deng Xuliang
Publication year - 2020
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.201901412
Subject(s) - microbiology and biotechnology , signal transduction , mapk/erk pathway , microrna , intracellular , cellular differentiation , stem cell , chemistry , downregulation and upregulation , regeneration (biology) , protein kinase a , kinase , biology , biochemistry , gene
Abstract Substrate topographical features induce osteogenic differentiation of bone marrow stem cells (BMSCs), but the underlying mechanisms are unclear. As microRNAs (miRNAs) play key roles in osteogenesis and bone regeneration, it would be meaningful to elucidate the roles of miRNAs in the intracellular signaling cascade of topographical cue‐induced osteogenic differentiation. In this study, the miRNA expression profile of the topographical feature‐induced osteogenic differentiation group is different from that of the chemical‐factors‐induced osteogenic differentiation group. miR‐193a‐3p is sensitive to substrate topographical features and its downregulation enhances osteogenic differentiation only in the absence of osteogenesis−inducing medium. Also, substrate topographical features specifically activate a nonclassical osteogenetic pathway—the mitogen‐activated protein kinase (MAPK) pathway. Loss‐ and gain‐of‐function experiments demonstrate that miR‐193a‐3p regulates the MAPK pathway by targeting the MAP3k3 gene. In conclusion, this data indicates that different osteogenic‐lineage‐related intracellular signaling cascades are triggered in BMSCs subjected to biophysical or chemical stimulation. Moreover, the miR‐193a‐3p‐MAP3k3 signaling axis plays a pivotal role in the transduction of biophysical cues from the substrate to regulate the osteogenic lineage specification of BMSCs, and hence may be a promising molecular target for bone regenerative therapies.