{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T19:28:46Z","timestamp":1781810926207,"version":"3.54.5"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2020,5,14]],"date-time":"2020-05-14T00:00:00Z","timestamp":1589414400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000341","name":"Arthritis Research UK","doi-asserted-by":"publisher","award":["MP\/19200"],"award-info":[{"award-number":["MP\/19200"]}],"id":[{"id":"10.13039\/501100000341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000833","name":"Rosetrees Trust","doi-asserted-by":"publisher","award":["A1726"],"award-info":[{"award-number":["A1726"]}],"id":[{"id":"10.13039\/501100000833","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["asbmr.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JBMR Plus"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The link between bone and blood vessels is regulated by hypoxia and the hypoxia\u2010inducible transcription factor, HIF, which drives both osteogenesis and angiogenesis. The recent clinical approval of PHD enzyme inhibitors, which stabilize HIF protein, introduces the potential for a new clinical strategy to treat osteolytic conditions such as osteoporosis, osteonecrosis, and skeletal fracture and nonunion. However, bone\u2010resorbing osteoclasts also play a central role in bone remodeling and pathological osteolysis, and HIF promotes osteoclast activation and bone loss in vitro. It is therefore likely that the result of PHD enzyme inhibition in vivo would be mediated by a balance between increased bone formation and increased bone resorption. It is essential that we improve our understanding of the effects of HIF on osteoclast formation and function and consider the potential contribution of inhibitory interactions with other musculoskeletal cells. The PHD enzyme inhibitor FG\u20104592 stabilized HIF protein and stimulated osteoclast\u2010mediated bone resorption, but inhibited differentiation of human CD14+ monocytes into osteoclasts. Formation of osteoclasts in a more physiologically relevant 3D collagen gel did not affect the sensitivity of osteoclastogenesis to FG\u20104592, but increased sensitivity to reduced concentrations of RANKL. Coculture with osteoblasts amplified inhibition of osteoclastogenesis by FG\u20104592, whether the osteoblasts were proliferating, differentiating, or in the presence of exogenous M\u2010CSF and RANKL. Osteoblast coculture dampened the ability of high concentrations of FG\u20104592 to increase bone resorption. These data provide support for the therapeutic use of PHD enzyme inhibitors to improve bone formation and\/or reduce bone loss for the treatment of osteolytic pathologies and indicate that FG\u20104592 might act in vivo to inhibit the formation and activity of the osteoclasts that drive osteolysis. \u00a9 2020 The Authors.\n                    <jats:italic>JBMR Plus<\/jats:italic>\n                    published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.\n                  <\/jats:p>","DOI":"10.1002\/jbm4.10370","type":"journal-article","created":{"date-parts":[[2020,4,29]],"date-time":"2020-04-29T13:08:40Z","timestamp":1588165720000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Osteoblast\u2013Osteoclast Coculture Amplifies Inhibitory Effects of\n                    <scp>FG<\/scp>\n                    \u20104592 on Human Osteoclastogenesis and Reduces Bone 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