XAF1 Promotes Osteoclast Apoptosis by Antagonizing the XIAP-caspase Axis

Overview

Journal J Orthop Translat

Publisher Elsevier

Specialty Orthopedics

Date 2024 Jul 3

PMID 38957269

Authors

Mingchao Zhang

Yingkang Huang

Jinyu Bai

Wushuang Xu

Huajian Shan

Lei Sheng

Xiang Gao

Yu Han

Shiyou Wang

Chaowen Bai

Bo Tian

Yichao Ni

Qirong Dong

Feng Ma

Xiaozhong Zhou

Affiliations

Soon will be listed here.

Abstract

Background: Over-activated osteoclast (OC) is a major cause of diseases related to bone loss and bone metabolism. Both bone resorption inhibition and apoptosis induction of osteoclast are crucial in treating these diseases. is an important interferon-stimulated and apoptotic gene. However, how regulates bone formation and remodeling is unknown.

Methods: We generate global and chimeric knockout mouse models and utilize these models to explore the function and mechanism of in regulating bone formation and remodeling and .

Results: We show that depletion enhances osteoclast generation . knockout increases osteoclast number and bone resorption, thereby exacerbating bone loss in both OVX and osteolysis models. Activation of XAF1 with BV6 (a potent XIAP inhibitor) suppresses osteoclast formation. Mechanistically, deletion decreases osteoclast apoptosis by facilitating the interaction between XIAP and caspase-3/7.

Conclusions: Our data illustrates an essential role of in controlling osteoclastogenesis in both osteoporosis and osteolysis mouse models and highlights its underlying mechanism, indicating a potential role in clinical treatment.The translational potential of this article: The translation potential of this article is that we first indicated that osteoclast apoptosis induced by XAF1 contribute to the progression of osteoporosis and osteolysis, which provides a novel strategy in the prevention of osteoporosis and osteolysis.

Citing Articles

Understanding pathophysiology and injury mechanisms is the foundation for invention/innovation and clinical translation in orthopaedics.

Qin L J Orthop Translat. 2024; 47:A1-A2.

PMID: 39161656 PMC: 11332985. DOI: 10.1016/j.jot.2024.07.003.

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