| Autor: |
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 |
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| Zdroj: |
Bone Research; 5/10/2022, Vol. 10 Issue 1, p1-12, 12p |
| Abstrakt: |
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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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