Effect of mitophagy in the formation of osteomorphs derived from osteoclasts

Tingben Huang; Yuchen Wang; Zhou Yu; Xiaoyan Miao; Zhiwei Jiang; Ke Yu; Mengdie Fu; Kaichen Lai; Ying Wang; Guoli Yang

doi:10.1016/j.isci.2023.106682

Effect of mitophagy in the formation of osteomorphs derived from osteoclasts

iScience. 2023 Apr 18;26(5):106682. doi: 10.1016/j.isci.2023.106682. eCollection 2023 May 19.

Authors

Tingben Huang^{1

2}, Yuchen Wang^{1

2}, Zhou Yu^{1

2}, Xiaoyan Miao¹, Zhiwei Jiang^{1

2}, Ke Yu^{1

2}, Mengdie Fu^{1

2}, Kaichen Lai^{1

2}, Ying Wang^{1

3}, Guoli Yang^{1

2}

Affiliations

¹ Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, Zhejiang 310006, China.
² Department of Implantology, The Affiliated Stomatology Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, China.
³ Department of Endodontics, The Affiliated Stomatology Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, China.

Abstract

Osteoclasts are specialized multinucleated giant cells with unique bone-destroying capacities. A recent study revealed that osteoclasts undergo an alternative cell fate by dividing into daughter cells called osteomorphs. To date, no studies have focused on the mechanisms of osteoclast fission. In this study, we analyzed the alternative cell fate process in vitro and, herein, reported the high expression of mitophagy-related proteins during osteoclast fission. Mitophagy was further confirmed by the colocalization of mitochondria with lysosomes, as observed in fluorescence images and transmission electron microscopy. We investigated the role played by mitophagy in osteoclast fission via drug stimulation experiments. The results showed that mitophagy promoted osteoclast division, and inhibition of mitophagy induced osteoclast apoptosis. In summary, this study reveals the role played by mitophagy as the decisive link in osteoclasts' fate, providing a new therapeutic target and perspective for the clinical treatment of osteoclast-related diseases.

Keywords: Functional aspects of cell biology; Molecular interaction; Specialized functions of cells.