ANGPTL4 binds to the leptin receptor to regulate ectopic bone formation.
Proc Natl Acad Sci U S A
; 121(1): e2310685120, 2024 Jan 02.
Article
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| MEDLINE
| ID: mdl-38147550
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 ANGPTL4 impeded chondrogenesis and HO in mice. Together, these findings identify ANGPTL4 as a ligand for LepR to regulate the formation of acquired HO.
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MEDLINE
Asunto principal:
Osificación Heterotópica
/
Leptina
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Animals
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En
Año:
2024
Tipo del documento:
Article