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

Zhang K, Qiu W, et al.

Journal of Orthopaedic Translation

Northwestern Polytechnical University, Xi'an Jiaotong University, Sichuan University

RESEARCH SUMMARY

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.

Mechanical testing of tibial bone strength was performed using a CellScale UniVert mechanical test system in a three-point bending configuration. The tibias were positioned with an 8 mm span and subjected to flexural loading at 0.6 mm/min until 0.5 mm displacement was reached. Load–displacement curves were used to determine stiffness, maximum load, and Young’s modulus. The 21-month-old MACF1-overexpressing mice exhibited increased maximum load and elastic modulus, confirming that MACF1 enhances bone toughness and strength during aging.

AUTHORS

Kewen Zhang, Wuxia Qiu, Hui Li, Jun Li, Pai Wang, Zhihao Chen, Xiao Lin, Airong Qian.

PUBLICATION DETAILS

JOURNAL

Journal of Orthopaedic Translation

YEAR

2023

INSTITUTIONS

Northwestern Polytechnical University, Xi'an Jiaotong University, Sichuan University

COUNTRIES

China

INSTRUMENT USED

UniVert

TESTING METHODS

Flexural and Bending Testing

RESEARCH APPLICATIONS

Bone Tissue Engineering & MechanicsMechanotransductionStem Cell Mechanobiology

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