Estrogen-mediated downregulation of HIF-1[alpha] signaling in B lymphocytes influences postmenopausal bone loss

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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

Location: Deutsche Nationalbibliothek Frankfurt am Main

Extent: Online-Ressource

Language: Englisch

Notes: Bone research. - 10, 1 (2022) , 15, ISSN: 2095-6231

Event: Veröffentlichung

(where): Freiburg

(who): Universität

(when): 2022

Creator: 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: 10.1038/s41413-022-00189-x

URN: urn:nbn:de:bsz:25-freidok-2249832

Rights: Kein Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.

Last update: 25.03.2025, 1:47 PM CET

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Associated

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

Time of origin

2022

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Estrogen-mediated downregulation of HIF-1[alpha] signaling in B lymphocytes influences postmenopausal bone loss

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Other Objects (12)

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