{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T01:27:34Z","timestamp":1790558854477,"version":"4.1.0"},"reference-count":59,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2009,1,30]],"date-time":"2009-01-30T00:00:00Z","timestamp":1233273600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2009,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Osteoclasts are the primary mediators of pathological bone resorption in many conditions in which micro\u2010environmental hypoxia is associated with disease progression. However, effects of hypoxia on human osteoclast activity have not been reported. Mature human osteoclasts were differentiated from peripheral blood or obtained from giant cell tumour of bone. Osteoclasts were exposed to a constant hypoxic environment and then assessed for parameters including resorption (toluidine blue staining of dentine slices), membrane integrity (trypan blue exclusion), apoptosis (TUNEL, DAPI), and osteolysis\u2010associated enzyme activity (TRAP, cathepsin K). 24 h exposure to 2% O\n                    <jats:sub>2<\/jats:sub>\n                    produced a 2.5\u2010fold increase in resorption associated with increased TRAP and cathepsin K enzyme activity. Hypoxia\u2010Inducible Factor\u20101\u03b1 (HIF\u20101\u03b1) siRNA completely ablated the hypoxic increase in osteoclast resorption. 24 h at 2% O\n                    <jats:sub>2<\/jats:sub>\n                    also increased the number of osteoclasts with compromised membrane integrity from 6% to 21%, with no change in the total osteoclast number or the proportion of late\u2010stage apoptotic cells. Transient reoxygenation returned the percentage of trypan blue\u2010positive cells to normoxic levels, suggesting that osteoclasts can recover from the early stages of cell death. Repeated over an extended period, hypoxia\/reoxygenation enhanced osteoclast differentiation at this\n                    <jats:italic>p<\/jats:italic>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    . These data suggest that in diseased bone, where the\n                    <jats:italic>p<\/jats:italic>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    may fall to \u22642% O\n                    <jats:sub>2<\/jats:sub>\n                    , a delicate balance between hypoxia\u2010induced osteoclast activation and hypoxia\u2010induced osteoclast apoptosis mediates pathological bone resorption. Copyright \u00a9 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.\n                  <\/jats:p>","DOI":"10.1002\/path.2534","type":"journal-article","created":{"date-parts":[[2009,1,30]],"date-time":"2009-01-30T14:34:05Z","timestamp":1233326045000},"page":"256-264","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":108,"title":["Acute hypoxia and osteoclast activity: a balance between enhanced resorption and increased apoptosis"],"prefix":"10.1002","volume":"218","author":[{"given":"Helen J","family":"Knowles","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas 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