MACF1 overexpression in BMSCs alleviates senile osteoporosis in mice through TCF4/miR-335–5p signaling pathway

• DOI: 10.1016/j.jot.2023.02.003
• Publication Date: 2023-03-15T17:45:11Z
• Authors: Kewen Zhang; Wuxia Qiu; Hui Li; Jun Li; Pai Wang; Zhihao Chen; Xiao Lin; Airong Qian
• Keywords: RUNX2; Osteonectin

The decreased osteogenic differentiation ability of mesenchymal stem cells (MSCs) is one the important reasons for SOP. Inhibition Wnt signaling in MSCs closely related to Microtubule actin crosslinking factor 1 (MACF1) an regulator Wnt/β-catenin signal transduction. However, whether specific expression MACF1 MSC regulates SOP and its mechanism remains unclear. We established MSC-specific Prrx1 (Prx1) promoter-driven conditional knock-in (MACF-KI) mice, naturally aged male ovariectomized female mice models. Micro-CT, H&E staining, double calcein labeling, three-point bending test were used explore effects on bone formation microstructure model. Bioinformatics analysis, ChIP-PCR, qPCR, ALP staining mechanisms MSCs' differentiation. Microarray analysis revealed that positive regulators pathway (such as TCF4, β-catenin, Dvl) was human (hMSCs) isolated from osteoporotic than non-osteoporotic patients. activity osteogenesis marker genes (Alp, Runx2, Bglap) mouse downregulated during aging. Furthermore, Micro-CT femur 2-month-old (MACF-cKI) showed no significant trabecular changes compared wild-type littermate controls, whereas 18- 21-month-old c-KI animals displayed increased mineral densities (BMD), improved microstructure, maximum compression stress. In addition, ovariectomy (OVX)-induced osteoporosis model had significantly higher volume number, rate control mice. Mechanistically, ChIP-PCR TCF4 could bind promoter region host gene miR-335–5p. Moreover, regulate miR-335–5p by MSCs. These data indicate positively through TCF4/miR-335-5p SOP, suggesting targeting may be a novel therapeutic approach against MACF1, switch pathway, can alleviate It might act target treatment improve function.