ANGPTL4 binds to the leptin receptor to regulate ectopic bone formation
成果类型：
Article
署名作者：
Hu, Hongling; Luo, Sheng; Lai, Pinglin; Lai, Mingqiang; Mao, Linlin; Zhang, Sheng; Jiang, Yuanjun; Wen, Jiaxin; Zhou, Wu; Liu, Xiaolin; Wang, Liang; Huang, Minjun; Hu, Yanjun; Zhao, Xiaoyang; Xia, Laixin; Zhou, Weijie; Jiang, Yu; Zou, Zhipeng; Liu, Anling; Guo, Bin; Bai, Xiaochun
署名单位：
Southern Medical University - China; Southern Medical University - China; Southern Medical University - China; Southern Medical University - China; Southern Medical University - China; Southern Medical University - China; Southern Medical University - China; Southern Medical University - China; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Southern Medical University - China
刊物名称：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN/ISSBN：
0027-14964
DOI：
10.1073/pnas.2310685120
发表日期：
2024-01-02
关键词：
angiopoietin-like 4
mesenchymal stromal cells
heterotopic ossification
chondrogenic differentiation
antiinflammatory drugs
proteins
promotes
proliferation
osteogenesis
osteoblasts
摘要：
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.