Estrogen-mediated downregulation of HIF-1[alpha] signaling in B lymphocytes influences postmenopausal bone loss
Abstract: 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
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Anmerkungen
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Bone research. - 10, 1 (2022) , 15, ISSN: 2095-6231
- Ereignis
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Veröffentlichung
- (wo)
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Freiburg
- (wer)
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Universität
- (wann)
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2022
- Urheber
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Meng, Xianyi
Lin, Zhen
Cao, Shan
Janowska, Iga
Sonomoto, Koshiro
Andreev, Darja
Knab, Katharina
Wen, Jinming
Knaup, Karl X.
Wiesener, Michael S.
Krönke, Gerhard
Rizzi, Marta
Schett, Georg
Bozec, Aline
- DOI
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10.1038/s41413-022-00189-x
- URN
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urn:nbn:de:bsz:25-freidok-2249832
- Rechteinformation
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Kein Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
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25.03.2025, 13:47 MEZ
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Beteiligte
- Meng, Xianyi
- Lin, Zhen
- Cao, Shan
- Janowska, Iga
- Sonomoto, Koshiro
- Andreev, Darja
- Knab, Katharina
- Wen, Jinming
- Knaup, Karl X.
- Wiesener, Michael S.
- Krönke, Gerhard
- Rizzi, Marta
- Schett, Georg
- Bozec, Aline
- Universität
Entstanden
- 2022
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