Estrogen-mediated downregulation of HIF-1α signaling in B lymphocytes influences postmenopausal bone loss
In the bone marrow, B cells and bone-resorbing osteoclasts colocalize and form a specific microenvironment. How B cells functionally influence osteoclasts and bone architecture is poorly understood. Using genetically modified mice and high-throughput analyses, we demonstrate that prolonged HIF-1α si...
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| Veröffentlicht in: | Bone Research 2022-02, Vol.10 (1), p.15-15, Article 15 |
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| creator | Meng, Xianyi Lin, Zhen Cao, Shan Janowska, Iga Sonomoto, Koshiro Andreev, Darja Katharina, Knab Wen, Jinming Knaup, Karl Xaver Wiesener, Michael Sean Krönke, Gerhard Rizzi, Marta Schett, Georg Bozec, Aline |
| description | In the bone marrow, B cells and bone-resorbing osteoclasts colocalize and form a specific microenvironment. How B cells functionally influence osteoclasts and bone architecture is poorly understood. Using genetically modified mice and high-throughput analyses, we demonstrate that prolonged HIF-1α signaling in B cells leads to enhanced RANKL production and osteoclast formation. In addition, deletion of HIF-1α in B cells prevents estrogen deficiency-induced bone loss in mice. Mechanistically, estrogen controls HIF-1α protein stabilization through HSP70-mediated degradation in bone marrow B cells. The stabilization of HIF-1α protein in HSP70-deficient bone marrow B cells promotes RANKL production and osteoclastogenesis. Induction of HSP70 expression by geranylgeranylacetone (GGA) administration alleviates ovariectomy-induced osteoporosis. Moreover,
RANKL
gene expression has a positive correlation with
HIF1A
expression in human B cells. In conclusion, HIF-1α signaling in B cells is crucial for the control of osteoclastogenesis, and the HSP70/HIF-1α axis may serve as a new therapeutic target for osteoporosis. |
| doi_str_mv | 10.1038/s41413-022-00189-x |
| format | Article |
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RANKL
gene expression has a positive correlation with
HIF1A
expression in human B cells. In conclusion, HIF-1α signaling in B cells is crucial for the control of osteoclastogenesis, and the HSP70/HIF-1α axis may serve as a new therapeutic target for osteoporosis.</description><identifier>ISSN: 2095-4700</identifier><identifier>ISSN: 2095-6231</identifier><identifier>EISSN: 2095-6231</identifier><identifier>DOI: 10.1038/s41413-022-00189-x</identifier><identifier>PMID: 35177582</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/443/63 ; 692/699/2743/316/801 ; Bone marrow ; Estrogens ; Gene expression ; Internal Medicine ; Medicine ; Medicine & Public Health ; Orthopedics ; Osteoporosis</subject><ispartof>Bone Research, 2022-02, Vol.10 (1), p.15-15, Article 15</ispartof><rights>The Author(s) 2022</rights><rights>2022. The Author(s).</rights><rights>The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c540t-569df04bdd5d7358bcf6ba903388b49b9b838e79330a3d029d3d05c3f7471b473</citedby><cites>FETCH-LOGICAL-c540t-569df04bdd5d7358bcf6ba903388b49b9b838e79330a3d029d3d05c3f7471b473</cites><orcidid>0000-0001-8174-2118 ; 0000-0002-7566-4325 ; 0000-0001-8740-9615</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8854586/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8854586/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,861,882,27905,27906,53772,53774</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35177582$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Meng, Xianyi</creatorcontrib><creatorcontrib>Lin, Zhen</creatorcontrib><creatorcontrib>Cao, Shan</creatorcontrib><creatorcontrib>Janowska, Iga</creatorcontrib><creatorcontrib>Sonomoto, Koshiro</creatorcontrib><creatorcontrib>Andreev, Darja</creatorcontrib><creatorcontrib>Katharina, Knab</creatorcontrib><creatorcontrib>Wen, Jinming</creatorcontrib><creatorcontrib>Knaup, Karl Xaver</creatorcontrib><creatorcontrib>Wiesener, Michael Sean</creatorcontrib><creatorcontrib>Krönke, Gerhard</creatorcontrib><creatorcontrib>Rizzi, Marta</creatorcontrib><creatorcontrib>Schett, Georg</creatorcontrib><creatorcontrib>Bozec, Aline</creatorcontrib><title>Estrogen-mediated downregulation of HIF-1α signaling in B lymphocytes influences postmenopausal bone loss</title><title>Bone Research</title><addtitle>Bone Res</addtitle><addtitle>Bone Res</addtitle><description>In the bone marrow, B cells and bone-resorbing osteoclasts colocalize and form a specific microenvironment. How B cells functionally influence osteoclasts and bone architecture is poorly understood. Using genetically modified mice and high-throughput analyses, we demonstrate that prolonged HIF-1α signaling in B cells leads to enhanced RANKL production and osteoclast formation. In addition, deletion of HIF-1α in B cells prevents estrogen deficiency-induced bone loss in mice. Mechanistically, estrogen controls HIF-1α protein stabilization through HSP70-mediated degradation in bone marrow B cells. The stabilization of HIF-1α protein in HSP70-deficient bone marrow B cells promotes RANKL production and osteoclastogenesis. Induction of HSP70 expression by geranylgeranylacetone (GGA) administration alleviates ovariectomy-induced osteoporosis. Moreover,
RANKL
gene expression has a positive correlation with
HIF1A
expression in human B cells. In conclusion, HIF-1α signaling in B cells is crucial for the control of osteoclastogenesis, and the HSP70/HIF-1α axis may serve as a new therapeutic target for osteoporosis.</description><subject>631/443/63</subject><subject>692/699/2743/316/801</subject><subject>Bone marrow</subject><subject>Estrogens</subject><subject>Gene expression</subject><subject>Internal Medicine</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Orthopedics</subject><subject>Osteoporosis</subject><issn>2095-4700</issn><issn>2095-6231</issn><issn>2095-6231</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>DOA</sourceid><recordid>eNp9ks1u1DAUhSMEolXpC7BAkdiwCfg3tjdIULV0pEpsYG3Z8U2akWMPdkI7j8WL8Ey4zVAoCza2de93j-2jU1UvMXqLEZXvMsMM0wYR0iCEpWpun1THBCnetITip4czEwgdVac5b1GhiGRK0ufVEeVYCC7JcbU9z3OKA4RmAjeaGVzt4k1IMCzezGMMdezry81Fg3_-qPM4BOPHMNRjqD_Wfj_trmO3nyGXQu8XCF057mKeJwhxZ5ZsfG1jgNrHnF9Uz3rjM5we9pPq68X5l7PL5urzp83Zh6um4wzNDW-V6xGzznEnKJe261trFKJUSsuUVVZSCUJRigx1iChXVt7RXjCBLRP0pNqsui6ard6lcTJpr6MZ9X0hpkGbNI-dB01d3zlKyyT0DEtrWoGB2tZKJ6BVULTer1q7xRaDOghzMv6R6ONOGK_1EL9rKTnjsi0Cbw4CKX5bIM96GnMH3psAccmatBQpggjnBX39D7qNSyqG31FEcYKLHYUiK9Wl4mmC_uExGOm7ZOg1GbokQ98nQ9-WoVd_f-Nh5HcOCkBXIJdWGCD9ufs_sr8AVj_GlQ</recordid><startdate>20220217</startdate><enddate>20220217</enddate><creator>Meng, Xianyi</creator><creator>Lin, Zhen</creator><creator>Cao, Shan</creator><creator>Janowska, Iga</creator><creator>Sonomoto, Koshiro</creator><creator>Andreev, Darja</creator><creator>Katharina, Knab</creator><creator>Wen, Jinming</creator><creator>Knaup, Karl Xaver</creator><creator>Wiesener, Michael Sean</creator><creator>Krönke, Gerhard</creator><creator>Rizzi, Marta</creator><creator>Schett, Georg</creator><creator>Bozec, Aline</creator><general>Nature Publishing Group UK</general><general>Springer Nature B.V</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0001-8174-2118</orcidid><orcidid>https://orcid.org/0000-0002-7566-4325</orcidid><orcidid>https://orcid.org/0000-0001-8740-9615</orcidid></search><sort><creationdate>20220217</creationdate><title>Estrogen-mediated downregulation of HIF-1α signaling in B lymphocytes influences postmenopausal bone loss</title><author>Meng, Xianyi ; 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How B cells functionally influence osteoclasts and bone architecture is poorly understood. Using genetically modified mice and high-throughput analyses, we demonstrate that prolonged HIF-1α signaling in B cells leads to enhanced RANKL production and osteoclast formation. In addition, deletion of HIF-1α in B cells prevents estrogen deficiency-induced bone loss in mice. Mechanistically, estrogen controls HIF-1α protein stabilization through HSP70-mediated degradation in bone marrow B cells. The stabilization of HIF-1α protein in HSP70-deficient bone marrow B cells promotes RANKL production and osteoclastogenesis. Induction of HSP70 expression by geranylgeranylacetone (GGA) administration alleviates ovariectomy-induced osteoporosis. Moreover,
RANKL
gene expression has a positive correlation with
HIF1A
expression in human B cells. In conclusion, HIF-1α signaling in B cells is crucial for the control of osteoclastogenesis, and the HSP70/HIF-1α axis may serve as a new therapeutic target for osteoporosis.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>35177582</pmid><doi>10.1038/s41413-022-00189-x</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0001-8174-2118</orcidid><orcidid>https://orcid.org/0000-0002-7566-4325</orcidid><orcidid>https://orcid.org/0000-0001-8740-9615</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 631/443/63 692/699/2743/316/801 Bone marrow Estrogens Gene expression Internal Medicine Medicine Medicine & Public Health Orthopedics Osteoporosis |
| title | Estrogen-mediated downregulation of HIF-1α signaling in B lymphocytes influences postmenopausal bone loss |
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