Advanced Science (Jul 2024)

Exploring the Link Between Autophagy‐Lysosomal Dysfunction and Early Heterotopic Ossification in Tendons

  • Chang‐He Gao,
  • Qian‐Qian Wan,
  • Jan‐Fei Yan,
  • Yi‐Na Zhu,
  • Lei Tian,
  • Jian‐Hua Wei,
  • Bin Feng,
  • Li‐Na Niu,
  • Kai Jiao

DOI
https://doi.org/10.1002/advs.202400790
Journal volume & issue
Vol. 11, no. 28
pp. n/a – n/a

Abstract

Read online

Abstract Heterotopic ossification (HO), the pathological formation of bone within soft tissues such as tendon and muscle, is a notable complication resulting from severe injury. While soft tissue injury is necessary for HO development, the specific molecular pathology responsible for trauma‐induced HO remains a mystery. The previous study detected abnormal autophagy function in the early stages of tendon HO. Nevertheless, it remains to be determined whether autophagy governs the process of HO generation. Here, trauma‐induced tendon HO model is used to investigate the relationship between autophagy and tendon calcification. In the early stages of tenotomy, it is observed that autophagic flux is significantly impaired and that blocking autophagic flux promoted the development of more rampant calcification. Moreover, Gt(ROSA)26sor transgenic mouse model experiments disclosed lysosomal acid dysfunction as chief reason behind impaired autophagic flux. Stimulating V‐ATPase activity reinstated both lysosomal acid functioning and autophagic flux, thereby reversing tendon HO. This present study demonstrates that autophagy‐lysosomal dysfunction triggers HO in the stages of tendon injury, with potential therapeutic targeting implications for HO.

Keywords