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Due to a specialized morphology and surrounding structure, osteocytes are more tolerant to hypoxia during osteoporosis, fracture, osteoarthritis, and orthodontic\u2013orthognathic combination therapy. Hypoxia\u2010inducible factor\u20101\u03b1 (HIF\u20101\u03b1) is one of the master regulators of hypoxia reactions, playing an important role in bone modeling, remodeling, and homeostasis. This study aimed to investigate the pivotal functional role of HIF\u20101\u03b1 in osteocytes initiating of bone remodeling under hypoxia. In the present study, the osteoclasts formation induced by RAW264.7 was significantly promoted in conditioned media (CM) from osteocytic MLO\u2010Y4 exposed to hypoxia in vitro. Therefore, hypoxic MLO\u2010Y4 cells simulated by 100\u2009\u03bcmol\/L CoCl\n                    <jats:sub>2<\/jats:sub>\n                    or 2% O\n                    <jats:sub>2<\/jats:sub>\n                    stably expressed HIF\u20101\u03b1 proteins and upregulated the expression of receptor activator of nuclear factor\u2010\u03baB ligand (RANKL) at both the messenger RNA (mRNA) and protein level. Furthermore, with the Knockdown of HIF\u20101\u03b1, the expression of RANKL mRNA and protein decreased after transient transfection. In addition, the phosphorylation of Janus kinase 2 (JAK2) and signal transducer and activator of transcription (STAT3) was also correlated with HIF\u20101\u03b1 and RANKL levels under hypoxia. Then AG490, a JAK2 inhibitor, inhibited p\u2010JAK2, p\u2010STAT3 and RANKL expression. It was possible that AG490 disturbed the contact of HIF\u20101\u03b1 and RANKL by JAK2\/STAT3 pathway, influencing osteoclastogenesis. Our findings suggested that HIF\u20101\u03b1 promoted the expression of RANKL by activating JAK2\/STAT3 pathway in MLO\u2010Y4 cells, and enhanced osteocyte\u2010mediated osteoclastic differentiation in vitro.\n                  <\/jats:p>","DOI":"10.1002\/jcp.28721","type":"journal-article","created":{"date-parts":[[2019,4,29]],"date-time":"2019-04-29T19:48:38Z","timestamp":1556567318000},"page":"21182-21192","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":104,"title":["HIF\u20101\u03b1 facilitates osteocyte\u2010mediated osteoclastogenesis by activating JAK2\/STAT3 pathway in vitro"],"prefix":"10.1002","volume":"234","author":[{"given":"Jie","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, School &amp; Hospital of Stomatology Tongji University Shanghai China"},{"name":"Shanghai Engineering Research Center of Tooth Restoration and Regeneration Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, School &amp; Hospital of Stomatology Tongji University Shanghai China"},{"name":"Shanghai Engineering Research Center of Tooth Restoration and Regeneration Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, School &amp; Hospital of Stomatology Tongji University Shanghai China"},{"name":"Shanghai Engineering Research Center of Tooth Restoration and Regeneration Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying\u2010Chen","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, School &amp; Hospital of Stomatology Tongji University Shanghai China"},{"name":"Shanghai Engineering Research Center of Tooth Restoration and Regeneration Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi\u2010Fan","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, School &amp; Hospital of Stomatology Tongji University Shanghai China"},{"name":"Shanghai Engineering Research Center of Tooth Restoration and Regeneration Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei\u2010Wu","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, School &amp; Hospital of Stomatology Tongji University Shanghai China"},{"name":"Shanghai Engineering Research Center of Tooth Restoration and Regeneration Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,4,29]]},"reference":[{"key":"e_1_2_9_1_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.23164"},{"key":"e_1_2_9_1_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2010.07.021"},{"key":"e_1_2_9_1_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.10321"},{"key":"e_1_2_9_1_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0105555"},{"key":"e_1_2_9_1_6_1","doi-asserted-by":"publisher","DOI":"10.1138\/20060233"},{"key":"e_1_2_9_1_7_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1402.018"},{"key":"e_1_2_9_1_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar4162"},{"key":"e_1_2_9_1_9_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1999.277.3.C598"},{"key":"e_1_2_9_1_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.20603"},{"key":"e_1_2_9_1_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2012.125"},{"key":"e_1_2_9_1_12_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-199610000-00015"},{"key":"e_1_2_9_1_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4899-7436-5_8"},{"key":"e_1_2_9_1_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V99.1.394"},{"key":"e_1_2_9_1_15_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.30.17771"},{"key":"e_1_2_9_1_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2015.02.002"},{"key":"e_1_2_9_1_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(02)00157-0"},{"key":"e_1_2_9_1_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20061467"},{"key":"e_1_2_9_1_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2012.10.013"},{"key":"e_1_2_9_1_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S8756-3282(97)00234-2"},{"issue":"2","key":"e_1_2_9_1_21_1","first-page":"S132","article-title":"Acute hypoxia and osteoclast activity: A balance between enhanced resorption and increased apoptosis","volume":"44","author":"Knowles H. 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