| First Author | Hu H | Year | 2024 |
| Journal | Proc Natl Acad Sci U S A | Volume | 121 |
| Issue | 1 | Pages | e2310685120 |
| PubMed ID | 38147550 | Mgi Jnum | J:353726 |
| Mgi Id | MGI:7662247 | Doi | 10.1073/pnas.2310685120 |
| Citation | Hu H, et al. (2024) ANGPTL4 binds to the leptin receptor to regulate ectopic bone formation. Proc Natl Acad Sci U S A 121(1):e2310685120 |
| abstractText | 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. |
