Inflammation and Regeneration (Jun 2024)

Emilin2 marks the target region for mesenchymal cell accumulation in bone regeneration

  • Yifan Qing,
  • Takehito Ono,
  • Yukihiro Kohara,
  • Atsushi Watanabe,
  • Noboru Ogiso,
  • Masako Ito,
  • Tomoki Nakashima,
  • Sunao Takeshita

DOI
https://doi.org/10.1186/s41232-024-00341-6
Journal volume & issue
Vol. 44, no. 1
pp. 1 – 15

Abstract

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Abstract Background Regeneration of injured tissue is dependent on stem/progenitor cells, which can undergo proliferation and maturation processes to replace the lost cells and extracellular matrix (ECM). Bone has a higher regenerative capacity than other tissues, with abundant mesenchymal progenitor cells in the bone marrow, periosteum, and surrounding muscle. However, the treatment of bone fractures is not always successful; a marked number of clinical case reports have described nonunion or delayed healing for various reasons. Supplementation of exogenous stem cells by stem cell therapy is anticipated to improve treatment outcomes; however, there are several drawbacks including the need for special devices for the expansion of stem cells outside the body, low rate of cell viability in the body after transplantation, and oncological complications. The use of endogenous stem/progenitor cells, instead of exogenous cells, would be a possible solution, but it is unclear how these cells migrate towards the injury site. Methods The chemoattractant capacity of the elastin microfibril interface located protein 2 (Emilin2), generated by macrophages, was identified by the migration assay and LC–MS/MS. The functions of Emilin2 in bone regeneration were further studied using Emilin2 –/– mice. Results The results show that in response to bone injury, there was an increase in Emilin2, an ECM protein. Produced by macrophages, Emilin2 exhibited chemoattractant properties towards mesenchymal cells. Emilin2 –/– mice underwent delayed bone regeneration, with a decrease in mesenchymal cells after injury. Local administration of recombinant Emilin2 protein enhanced bone regeneration. Conclusion Emilin2 plays a crucial role in bone regeneration by increasing mesenchymal cells. Therefore, Emilin2 can be used for the treatment of bone fracture by recruiting endogenous progenitor cells.

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