ANGPTL4 binds to the leptin receptor to regulate ectopic bone formation

Hongling Hu; Sheng Luo; Pinglin Lai; Mingqiang Lai; Linlin Mao; Sheng Zhang; Yuanjun Jiang; Jiaxin Wen; Wu Zhou; Xiaolin Liu; Liang Wang; Minjun Huang; Yanjun Hu; Xiaoyang Zhao; Laixin Xia; Weijie Zhou; Yu Jiang; Zhipeng Zou; Anling Liu; Bin Guo; Xiaochun Bai

doi:10.1073/pnas.2310685120

ANGPTL4 binds to the leptin receptor to regulate ectopic bone formation

Hongling Hu, Sheng Luo, Pinglin Lai, Mingqiang Lai, Linlin Mao, Sheng Zhang, Yuanjun Jiang, Jiaxin Wen, Wu Zhou, Xiaolin Liu, Liang Wang, Minjun Huang, Yanjun Hu, Xiaoyang Zhao, Laixin Xia, Weijie Zhou, Yu Jiang, Zhipeng Zou, Anling Liu^*, Bin GuoXiaochun Bai^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

5 Citations (Scopus)

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.

Original language	English
Article number	e2310685120
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	121
Issue number	1
DOIs	https://doi.org/10.1073/pnas.2310685120
Publication status	Published - 2024
Externally published	Yes

Keywords

ANGPTL4
heterotopic ossification
leptin receptor

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1073/pnas.2310685120

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Hu, H., Luo, S., Lai, P., Lai, M., Mao, L., Zhang, S., Jiang, Y., Wen, J., Zhou, W., Liu, X., Wang, L., Huang, M., Hu, Y., Zhao, X., Xia, L., Zhou, W., Jiang, Y., Zou, Z., Liu, A., ... Bai, X. (2024). ANGPTL4 binds to the leptin receptor to regulate ectopic bone formation. Proceedings of the National Academy of Sciences of the United States of America, 121(1), Article e2310685120. https://doi.org/10.1073/pnas.2310685120

@article{e9347223e6834eee81c8db6f3cfd2675,

title = "ANGPTL4 binds to the leptin receptor to regulate ectopic bone formation",

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.",

keywords = "ANGPTL4, heterotopic ossification, leptin receptor",

author = "Hongling Hu and Sheng Luo and Pinglin Lai and Mingqiang Lai and Linlin Mao and Sheng Zhang and Yuanjun Jiang and Jiaxin Wen and Wu Zhou and Xiaolin Liu and Liang Wang and Minjun Huang and Yanjun Hu and Xiaoyang Zhao and Laixin Xia and Weijie Zhou and Yu Jiang and Zhipeng Zou and Anling Liu and Bin Guo and Xiaochun Bai",

note = "Publisher Copyright: Copyright {\textcopyright} 2023 the Author(s). Published by PNAS.",

year = "2024",

doi = "10.1073/pnas.2310685120",

language = "English",

volume = "121",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

issn = "0027-8424",

number = "1",

}

Hu, H, Luo, S, Lai, P, Lai, M, Mao, L, Zhang, S, Jiang, Y, Wen, J, Zhou, W, Liu, X, Wang, L, Huang, M, Hu, Y, Zhao, X, Xia, L, Zhou, W, Jiang, Y, Zou, Z, Liu, A, Guo, B & Bai, X 2024, 'ANGPTL4 binds to the leptin receptor to regulate ectopic bone formation', Proceedings of the National Academy of Sciences of the United States of America, vol. 121, no. 1, e2310685120. https://doi.org/10.1073/pnas.2310685120

TY - JOUR

T1 - ANGPTL4 binds to the leptin receptor to regulate ectopic bone formation

AU - Hu, Hongling

AU - Luo, Sheng

AU - Lai, Pinglin

AU - Lai, Mingqiang

AU - Mao, Linlin

AU - Zhang, Sheng

AU - Jiang, Yuanjun

AU - Wen, Jiaxin

AU - Zhou, Wu

AU - Liu, Xiaolin

AU - Wang, Liang

AU - Huang, Minjun

AU - Hu, Yanjun

AU - Zhao, Xiaoyang

AU - Xia, Laixin

AU - Zhou, Weijie

AU - Jiang, Yu

AU - Zou, Zhipeng

AU - Liu, Anling

AU - Guo, Bin

AU - Bai, Xiaochun

PY - 2024

Y1 - 2024

N2 - 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.

AB - 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.

KW - ANGPTL4

KW - heterotopic ossification

KW - leptin receptor

UR - http://www.scopus.com/inward/record.url?scp=85180870985&partnerID=8YFLogxK

U2 - 10.1073/pnas.2310685120

DO - 10.1073/pnas.2310685120

M3 - Article

C2 - 38147550

AN - SCOPUS:85180870985

SN - 0027-8424

VL - 121

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 1

M1 - e2310685120

ER -

ANGPTL4 binds to the leptin receptor to regulate ectopic bone formation

Abstract

Keywords

UN SDGs

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