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

This study investigated how microtubule actin crosslinking factor 1 (MACF1) regulates osteogenic differentiation and bone formation in age-related (senile) osteoporosis. The researchers generated mesenchymal stem cell (MSC)-specific MACF1 overexpression mice and demonstrated that elevated MACF1 expression enhanced bone mineral density, trabecular microarchitecture, and bone strength in naturally aged and ovariectomized (OVX) models. Mechanistic studies revealed that MACF1 activates the Wnt/β-catenin pathway via TCF4, which transcriptionally induces miR-335–5p, thereby promoting osteogenesis and suppressing bone loss. These findings identify the MACF1–TCF4/miR-335–5p axis as a key regulatory pathway mitigating senile osteoporosis.