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

doi:10.1016/j.isci.2024.111042

Irisin reduces senile osteoporosis by inducing osteocyte mitophagy through Ampk activation

iScience. 2024 Sep 26;27(11):111042. doi: 10.1016/j.isci.2024.111042. eCollection 2024 Nov 15.

Authors

Honghan Li¹, Deqing Luo², Wei Xie², Wenbin Ye¹, Jinlong Chen¹, Paolo Alberton³, Mingzhu Zhang⁴, Eryou Feng⁵, Denitsa Docheva⁶, Dasheng Lin⁵

Affiliations

¹ Department of Orthopaedic Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, P.R. China.
² Department of Orthopaedics, the 909th Hospital, School of Medicine, Xiamen University, Zhangzhou, P.R. China.
³ Experimental Surgery and Regenerative Medicine, Clinic for General, Trauma and Reconstructive Surgery, Ludwig-Maximilians-University (LMU), Munich, Germany.
⁴ Center of Foot and Ankle Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, P.R. China.
⁵ Department of Orthopedic Surgery, Fujian Medical University Union Hospital, Fuzhou, P.R. China.
⁶ Department of Musculoskeletal Tissue Regeneration Orthopaedic Hospital König-Ludwig-Haus & University of Wuerzburg, Wuerzburg, Germany.

Abstract

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.

Keywords: Biological sciences; Molecular biology; Physiology.