ANGPTL4 acts as an alternative ligand for the leptin receptor on PRRX1+ mesenchymal cells to promote chondrogenesis and heterotopic ossification development in mice.
Identifies ANGPTL4 as a novel ligand for the leptin receptor that regulates acquired heterotopic ossification.
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 ANGPTL4 impeded chondrogenesis and HO in mice. Together, these findings identify ANGPTL4 as a ligand for LepR to regulate the formation of acquired HO.
Hu et al. (Tue,) conducted a other in Heterotopic ossification. ANGPTL4 deletion or LepR disruption vs. Control mice was evaluated on Chondrogenesis and heterotopic ossification development. ANGPTL4 acts as an alternative ligand for the leptin receptor on PRRX1+ mesenchymal cells to promote chondrogenesis and heterotopic ossification development in mice.