ANGPTL4 binds to the leptin receptor to regulate ectopic bone formation.

ABSTRACT: Leptin protein was thought to be unique to leptin receptor (LepR), but the phenotypes of mice with mutation in LepR [db/db (diabetes)] and leptin [ob/ob (obese)] are not identical, and the cause remains unclear. Here, we show that db/db, but not ob/ob, mice had defect in tenotomy-induced heterotopic ossification (HO), implicating alternative ligand(s) for LepR might be involved. Ligand screening revealed that ANGPTL4 (angiopoietin-like protein 4), a stress and fasting-induced factor, was elicited from brown adipose tissue after tenotomy, bound to LepR on PRRX1⁺ mesenchymal cells at the HO site, thus promotes chondrogenesis and HO development. Disruption of LepR in PRRX1⁺ cells, or lineage ablation of LepR⁺ cells, or deletion of A

SUBMITTER: Hu H 

PROVIDER: S-EPMC10769826 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature