In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 121, No. 1 ( 2024-01-02)
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.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.2310685120
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2024
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12