Meng X, Lin Z, Cao S, Janowska I, Sonomoto K, Andreev D, Knab K, Wen J, Knaup K, Krönke G, Rizzi M, Schett G, Bozec A, Wiesener M (2022)
Publication Type: Journal article
Publication year: 2022
Book Volume: 10
Journal Issue: 1
DOI: 10.1038/s41413-022-00189-x
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-1 alpha signaling in B cells leads to enhanced RANKL production and osteoclast formation. In addition, deletion of HIF-1 alpha in B cells prevents estrogen deficiency-induced bone loss in mice. Mechanistically, estrogen controls HIF-1 alpha protein stabilization through HSP70-mediated degradation in bone marrow B cells. The stabilization of HIF-1 alpha 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-1 alpha signaling in B cells is crucial for the control of osteoclastogenesis, and the HSP70/HIF-1 alpha axis may serve as a new therapeutic target for osteoporosis.
APA:
Meng, X., Lin, Z., Cao, S., Janowska, I., Sonomoto, K., Andreev, D.,... Wiesener, M. (2022). Estrogen-mediated downregulation of HIF-1 alpha signaling in B lymphocytes influences postmenopausal bone loss. Bone Research, 10(1). https://doi.org/10.1038/s41413-022-00189-x
MLA:
Meng, Xianyi, et al. "Estrogen-mediated downregulation of HIF-1 alpha signaling in B lymphocytes influences postmenopausal bone loss." Bone Research 10.1 (2022).
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