Author(s): CHEN, N., JIA, M., WU, T., CHENG, R., Institution: WUHAN SPORTS UNIVERSITY, Country: CHINA, Abstract-ID: 224

INTRODUCTION:
Postmenopausal osteoporosis (PMO) is a prevalent bone disorder characterized by estrogen deficiency-induced bone loss. Although exercise is known to ameliorate PMO, the underlying molecular mechanisms, particularly the role of muscle-derived myokines such as Irisin, remain poorly understood.
METHODS:
An ovariectomy (OVX)-induced PMO mouse model was established and the PMO mice were subjected to 8 weeks of aerobic or resistance exercise. Bone microarchitecture was assessed via micro-CT, while osteogenic markers and irisin expression were evaluated through histology, qPCR, and ELISA. The role of Irisin was further investigated using muscle-specific Fndc5 knockout mice, recombinant Irisin administration, and co-immunoprecipitation followed by mass spectrometry (Co-IP-MS).
RESULTS:
Both exercise modalities significantly improved bone microarchitecture and upregulated osteogenic markers, concomitant with increased irisin expression in muscle and serum. Exogenous irisin enhanced osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in vitro, while muscle-specific deletion of Fndc5 abolished exercise-induced bone gains. Co-IP-MS identified a direct physical interaction between irisin and alkaline phosphatase (ALP).
CONCLUSION:
This study clarifies muscle-derived irisin as a critical mediator of exercise-induced bone formation in PMO and reveals a novel irisin–ALP interaction as a potential regulatory mechanism. These findings highlight the therapeutic potential of irisin-based strategies and support the optimization of exercise regimens for osteoporosis management.