Targeting local lymphatics to ameliorate heterotopic ossification via FGFR3-BMPR1a pathway.

ABSTRACT: Acquired heterotopic ossification (HO) is the extraskeletal bone formation after trauma. Various mesenchymal progenitors are reported to participate in ectopic bone formation. Here we induce acquired HO in mice by Achilles tenotomy and observe that conditional knockout (cKO) of fibroblast growth factor receptor 3 (FGFR3) in Col2⁺ cells promote acquired HO development. Lineage tracing studies reveal that Col2⁺ cells adopt fate of lymphatic endothelial cells (LECs) instead of chondrocytes or osteoblasts during HO development. FGFR3 cKO in Prox1⁺ LECs causes even more aggravated HO formation. We further demonstrate that FGFR3 deficiency in LECs leads to decreased local lymphatic formation in a BMPR1a-pSmad1/5-dependent manner, which exacerbates inflammatory le

SUBMITTER: Zhang D 

PROVIDER: S-EPMC8289847 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature