MOTS‑c is a tiny protein made by mitochondria that helps protect cells and manage energy. New research shows it can make bone‑building cells grow and turn into bone, while also slowing down the cells that break bone down. Exercise naturally raises MOTS‑c levels, but we still don’t know exactly how this works in bone. The review suggests MOTS‑c could become a target for preventing or treating bone‑related metabolic problems.

MOTS-c, a mitochondrial-derived peptide (MDP), is an essential regulatory mediator of cell protection and energy metabolism and is involved in the development of specific diseases. Recent studies have revealed that MOTS-c promotes osteoblast proliferation, differentiation, and mineralization. Furthermore, it inhibits osteoclast production and mediates the regulation of bone metabolism and bone remodeling. Exercise effectively upregulates the expression of MOTS-c, but the specific mechanism of MOTS-c regulation in bone by exercise remains unclear. Therefore, this article reviewed the distribution and function of MOTS-c in the tissue, discussed the latest research developments in the regulation of osteoblasts and osteoclasts, and proposed potential molecular mechanisms for the effect of exercise on the regulation of bone metabolism. This review provides a theoretical reference for establishing methods to prevent and treat skeletal metabolic diseases.