@article{f08710cc775c467885406c4047ba3b68,
title = "IFT80 negatively regulates osteoclast differentiation via association with Cbl-b to disrupt TRAF6 stabilization and activation",
abstract = "Excess bone loss due to increased osteoclastogenesis is a significant clinical problem. Intraflagellar transport (IFT) proteins have been reported to regulate cell growth and differentiation. The role of IFT80, an IFT complex B protein, in osteoclasts (OCs) is completely unknown. Here, we demonstrate that deletion of IFT80 in the myeloid lineage led to increased OC formation and activity accompanied by severe bone loss in mice. IFT80 regulated OC formation by associating with Casitas B-lineage lymphoma protooncogene- b (Cbl-b) to promote protein stabilization and proteasomal degradation of tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6). IFT80 knockdown resulted in increased ubiquitination of Cbl-b and higher TRAF6 levels, thereby hyperactivating the receptor activator of nuclear factor-κβ (NF-κβ) ligand (RANKL) signaling axis and increased OC formation. Ectopic overexpression of IFT80 rescued osteolysis in a calvarial model of bone loss.We have thus identified a negative function of IFT80 in OCs.",
keywords = "IFT80, bone, osteoblast, osteoclast",
author = "Vishwa Deepak and Yang, {Shu Ting} and Ziqing Li and Xinhua Li and Andrew Ng and Ding Xu and Li, {Yi Ping} and Oursler, {Merry Jo} and Shuying Yang",
note = "Funding Information: ACKNOWLEDGMENTS. We acknowledge the assistance of the Penn Center for Musculoskeletal Disorders for providing access to the μCT instrument (NIH/ National Institute of Arthritis and Musculoskeletal and Skin Diseases [NIAMS] P30 AR069619). Research reported in this publication was supported by the National Institute of Dental and Craniofacial Research, NIAMS, and National Institute on Aging, part of the NIH, under Awards DE023105, AR066101, and AG048388 (to S.Y.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Funding Information: We acknowledge the assistance of the Penn Center for Musculoskeletal Disorders for providing access to the μCT instrument (NIH/ National Institute of Arthritis and Musculoskeletal and Skin Diseases [NIAMS] P30 AR069619). Research reported in this publication was supported by the National Institute of Dental and Craniofacial Research, NIAMS, and National Institute on Aging, part of the NIH, under Awards DE023105, AR066101, and AG048388 (to S.Y.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Publisher Copyright: Copyright {\textcopyright} 2022 the Author(s).",
year = "2022",
month = jun,
day = "28",
doi = "10.1073/pnas.2201490119",
language = "English (US)",
volume = "119",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "26",
}