Focused low-intensity pulsed ultrasound alleviates osteoarthritis via restoring impaired FUNDC1-mediated mitophagy

Haixia Ye; Dongqian Li; Xia Wei; Lehua Yu; Lang Jia

doi:10.1016/j.isci.2023.107772

Focused low-intensity pulsed ultrasound alleviates osteoarthritis via restoring impaired FUNDC1-mediated mitophagy

iScience. 2023 Aug 30;26(10):107772. doi: 10.1016/j.isci.2023.107772. eCollection 2023 Oct 20.

Authors

Haixia Ye^{1

2}, Dongqian Li¹, Xia Wei¹, Lehua Yu¹, Lang Jia¹

Affiliations

¹ Department of Rehabilitation Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
² Department of Rehabilitation Teaching and Research, Chongqing City Management College, Chongqing 401331, China.

Abstract

Mitophagy is critical for maintaining proper cellular functions, and it contributes to the onset and progression of osteoarthritis (OA). A recent study showed that focused low-intensity pulsed ultrasound (FLIPUS) could activate mitophagy, but the molecular mechanism remains unclear. This study aimed to elucidate the chondroprotective effects of FLIPUS in OA and the regulatory effects on FUN14-domain containing 1 (FUNDC1-mediated mitophagy. In vitro, FLIPUS improved inflammatory response, anabolism, and catabolism in interleukin (IL)-1β-induced OA chondrocytes. The chondroprotective effects of FLIPUS were attributed to promoting the expression of phosphoglycerate mutase 5 (PGAM5) and the dephosphorylation of FUNDC1 at serine 13 (Ser13), as well as promoting the mitophagy process. In vivo, FLIPUS reduced the cartilage degeneration and apoptosis and reversed the change of anabolic- and catabolic-related proteins in destabilized medial meniscus (DMM)-induced mouse model. Thus, the study indicates that FLIPUS exhibits a chondroprotective effect via activating impaired FUNDC1-mediated mitophagy.

Keywords: Disease; Immunology; Molecular biology.