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However, the involvement of ATG in bone and bone-related cells remains unclear. Here, we show that Beclin1, an ATG-related protein involved in ATG initiation, plays a pivotal role in osteoclasts. ATG was activated during osteoclast differentiation in vitro. Beclin1 was enhanced and required for osteoclast differentiation. Mechanistically, we found that TRAF6-mediated ubiquitination of Beclin1 at K117, but not ULK1-mediated phosphorylation, is required for RANKL-stimulated osteoclast differentiation. In vivo, mice lacking Beclin1 in CstK-expressing cells exhibited an increased cortical bone thickness caused by impaired osteoclasts\u2019 function. Interestingly, these mice also exhibited diminished trabecular bone mass, which was associated with a defect in cartilage formation and chondrocyte differentiation. Collectively, our study highlights the functional importance of ATG in osteoclasts and chondrocytes, and identifies ATG as a potential therapeutic target for managing bone-related diseases. \u00a9 2019 American Society for Bone and Mineral Research.<\/jats:p>","DOI":"10.1002\/jbmr.3756","type":"journal-article","created":{"date-parts":[[2019,5,10]],"date-time":"2019-05-10T13:30:06Z","timestamp":1557495006000},"page":"1753-1766","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":87,"title":["Beclin1 Modulates Bone Homeostasis by Regulating Osteoclast and Chondrocyte Differentiation"],"prefix":"10.1093","volume":"34","author":[{"given":"Atsushi","family":"Arai","sequence":"first","affiliation":[{"name":"Institute for Oral Science, Department of Orthodontics Matsumoto Dental University Nagano 399-0781 Japan"},{"name":"Laboratory of Molecular Signaling, Division of Oral Biology and Medicine, School of Dentistry and Broad Stem Cell 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