Irisin reduces senile osteoporosis by inducing osteocyte mitophagy through Ampk activation
Honghan Li,
Deqing Luo,
Wei Xie,
Wenbin Ye,
Jinlong Chen,
Paolo Alberton,
Mingzhu Zhang,
Eryou Feng,
Denitsa Docheva,
Dasheng Lin
Affiliations
Honghan Li
Department of Orthopaedic Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, P.R. China
Deqing Luo
Department of Orthopaedics, the 909th Hospital, School of Medicine, Xiamen University, Zhangzhou, P.R. China
Wei Xie
Department of Orthopaedics, the 909th Hospital, School of Medicine, Xiamen University, Zhangzhou, P.R. China
Wenbin Ye
Department of Orthopaedic Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, P.R. China
Jinlong Chen
Department of Orthopaedic Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, P.R. China
Paolo Alberton
Experimental Surgery and Regenerative Medicine, Clinic for General, Trauma and Reconstructive Surgery, Ludwig-Maximilians-University (LMU), Munich, Germany
Mingzhu Zhang
Center of Foot and Ankle Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, P.R. China
Eryou Feng
Department of Orthopedic Surgery, Fujian Medical University Union Hospital, Fuzhou, P.R. China
Denitsa Docheva
Department of Musculoskeletal Tissue Regeneration Orthopaedic Hospital König-Ludwig-Haus & University of Wuerzburg, Wuerzburg, Germany
Dasheng Lin
Department of Orthopedic Surgery, Fujian Medical University Union Hospital, Fuzhou, P.R. China; Corresponding author
Summary: Irisin, an exercise-induced myokine, is known to be able to regulate bone metabolism. However, the underlying mechanisms regarding the effects of irisin on senile osteoporosis have not been fully elucidated. Here, we demonstrated that irisin can inhibit bone mass loss and bone microarchitecture alteration in senile osteoporosis mouse model. In addition, irisin has effects on bone remodeling that is in favor of bone formation. Remarkably, irisin induced autophagy in osteocytes demonstrated by increased LC3-positive osteocytes, and increased autophagy-related genes and proteins. In vitro analysis revealed that Irisin can prevent mitochondrial oxidative damage. Furthermore, irisin can obviously induce osteocyte mitophagy and increased phosphorylation of Ampk and Ulk1. Inhibition of Ampk signaling recapitulated the biological effect of irisin loss, accompanied by the markedly lower expression of Ulk1. Taken together, our findings show that irisin reduces age-related bone loss by inducing osteocyte mitophagy via Ampk-dependent activation of Ulk1.
