MMP2 promotes osteoblast differentiation and calcification of muscle-derived mesenchymal stem cells by interaction with miR-29b-3p. (June 2022)

• Record Type: Journal Article
• Authors: Zhong-Sheng, Zhu; Nuo, Yin; Xiao-Yan, Huang; Liang, Ding; Rui, Fang; Hai-Jun, Xiao
• Is Part Of: Tissue & cell. Volume 76(2022)
• Publication Date: 2022-06
• Subjects: MMP2 -- M-MSC -- MiRNA-29b-3p -- Osteoblast differentiation -- Calcification; Cytology -- Periodicals; 571.5
• DOI: 10.1016/j.tice.2022.101807
• Languages: English
• ISSNs: 0040-8166

Abstract

Abstract: Matrix metalloproteinase 2 (MMP2) was previously reported to play important role in the process of stem cell migration and various differentiation behaviors of muscle-derived mesenchymal stem cells (M-MSCs). However, its role and regulatory mechanism in the osteoblast differentiation and calcification of M-MSCs remain unclear. In the current study, we found that MMP2 could facilitate the osteoblast differentiation and calcification of muscle-derived mesenchymal stem cells by up-regulating the expression of some typical osteogenic differentiation phenotype markers, such as runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP), and osteocalcin (OCN). Besides, we further demonstrated that MMP2 could be directly targeted by miRNA-29b-3p, which was validated by dual luciferase reporter gene and rescue assays. Moreover, increased expression of MMP2 could contribute to forming more calcium nodules representative for osteoblast calcification verified by the alizarin red staining, vice versa. In conclusion, we identified the role of miRNA-29b-3p/MMP2 relationship in regulating osteoblast differentiation and calcification of M-MSCs, which may complement the effect of MMPs family on the osteoblast differentiation to some extent, providing some potential clinical application value in the promotion of bone formation in the future. Highlights: MMP2 could facilitate the osteoblast differentiation and calcification of M-MSCs. MMP2 could up-regulate the expression of RUNX2, OCN and ALP. MMP2 could be directly targeted and regulated by miRNA-29b-3p.