Excessive DAO inhibits myoblast migration, leading to impaired myotube fusion and muscle strength decline by reducing ECM

Xiang Liu¹Jianchao Xue²Yiming Liang¹Zhenggang Li¹Rui Xu¹Huaimei Yang¹YU ZHAO²Qiyang Wang¹Jianhong Hou^1*Sheng Lu^1*

• ¹Department of Orthopedics, the First People’s Hospital of Yunnan Province & the Affiliated Hospital of Kunming University of Science and Technology, Kunming, China
• ²Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

The molecular underpinnings of muscle strength decline remain elusive. While omics studies have suggested a potential link between AOC1 (amine oxidase copper-containing 1, encoded DAO protein) and muscle weakness, experimental validation and mechanistic insights are lacking. By testing serum DAO levels, we got the clinical association between serum DAO levels and grip strength in elderly males (n = 81, p < 0.05), but not in females (n = 48), aligning with sarcopenia-associated fast fiber loss in Lab mice models. Except the alter of myofiber, in vitro, recombinant human DAO protein (100–200 pg/ml) inhibited C2C12 myoblast migration and fusion without cytotoxicity was observed. Under the hint from Mass Spectrometry, DAO maybe disturb cell migration and fusion by binding Fbln1, suppressing FAK phosphorylation (Y576/Y577) and cytoskeletal remodeling. This study provides the experimental evidence linking DAO to muscle weakness through metabolic-biomechanical uncoupling—promoting fast fiber loss and sabotaging Fbln1/FAK-driven myogenesis.