MACF1 overexpression in BMSCs alleviates senile osteoporosis in mice through TCF4/miR-335–5p signaling pathway
RUNX2
Osteonectin
DOI:
10.1016/j.jot.2023.02.003
Publication Date:
2023-03-15T17:45:11Z
AUTHORS (8)
ABSTRACT
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.
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