FATP2 regulates osteoclastogenesis by increasing lipid metabolism and ROS production

Kong, Xiangxi
Tao, Siyue
Ji, Zhongyin
Li, Jie
Li, Hui
Jin, Jiayan
Zhao, Yihao
Liu, Junhui
Zhao, Fengdong
Chen, Jian
Feng, Zhenhua
Chen, Binhui
Shan, Zhi

Department of Orthopaedic Surgery, Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Hangzhou, 310016, Zhejiang, China
Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province, Hangzhou 310016, Zhejiang, China
Department of Orthopaedic Surgery, Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Hangzhou, 310016, Zhejiang, China
Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province, Hangzhou 310016, Zhejiang, China
Department of Orthopaedic Surgery, Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Hangzhou, 310016, Zhejiang, China
Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province, Hangzhou 310016, Zhejiang, China
Department of Orthopaedic Surgery, Ningbo Medical Center Li Huili Hospital, Ningbo, 315100, Zhejiang, China
Department of Orthopaedic Surgery, Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Hangzhou, 310016, Zhejiang, China
Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province, Hangzhou 310016, Zhejiang, China
Department of Orthopaedic Surgery, Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Hangzhou, 310016, Zhejiang, China
Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province, Hangzhou 310016, Zhejiang, China
Department of Orthopaedic Surgery, Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Hangzhou, 310016, Zhejiang, China
Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province, Hangzhou 310016, Zhejiang, China
Department of Orthopaedic Surgery, Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Hangzhou, 310016, Zhejiang, China
Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province, Hangzhou 310016, Zhejiang, China
Department of Orthopaedic Surgery, Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Hangzhou, 310016, Zhejiang, China
Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province, Hangzhou 310016, Zhejiang, China
Department of Orthopaedic Surgery, Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Hangzhou, 310016, Zhejiang, China
Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province, Hangzhou 310016, Zhejiang, China
Department of Orthopaedic Surgery, Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Hangzhou, 310016, Zhejiang, China
Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province, Hangzhou 310016, Zhejiang, China
Department of Orthopaedic Surgery, Ningbo Medical Center Li Huili Hospital, Ningbo, 315100, Zhejiang, China
Department of Orthopaedic Surgery, Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Hangzhou, 310016, Zhejiang, China
Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province, Hangzhou 310016, Zhejiang, China

Corresponding authors: Zhi Shan, No. 3, Qingchun Road East, Hangzhou 310016, Zhejiang, China ([email protected]); Binhui Chen, No. 1111, Jiangnan Road, Ningbo 315100, Zhejiang, China ([email protected]); Zhenhua Feng, No. 3, Qingchun Road East, Hangzhou 310016, Zhejiang, China ([email protected]).

Xiangxi Kong, Siyue Tao and Zhongyin Ji contributed equally to this work.

Received June 27, 2023

Received in revised form February 05, 2024

Accepted February 13, 2024

Revised April 20, 2024

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/pages/standard-publication-reuse-rights)

Journal of Bone & Mineral Research 39(6):p 737-752, June 2024. | DOI: 10.1093/jbmr/zjae034

Lay Summary

The inhibition of osteoclastogenesis by Lipofermata, a FATP2 inhibitor, was achieved through the reprogramming of energy metabolism and regulation of ROS levels. In both pathological bone loss and HFD-induced osteoporosis models, the expression levels of FATP2 were significantly upregulated, and Lipofermata demonstrated potential therapeutic effects in the pathological bone loss model.