典型文献
Estrogen-mediated downregulation of HIF-1α signaling in B lymphocytes influences postmenopausal bone loss
文献摘要：
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-1αsignaling 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.
文献关键词：
中图分类号：
作者姓名：
Xianyi Meng;Zhen Lin;Shan Cao;Iga Janowska;Koshiro Sonomoto;Darja Andreev;Knab Katharina;Jinming Wen;Karl Xaver Knaup;Michael Sean Wiesener;Gerhard Kr?nke;Marta Rizzi;Georg Schett;Aline Bozec
作者机构：
Department of Internal Medicine 3,Friedrich-Alexander-University Erlangen-Nürnberg(FAU)and Universit?tsklinikum Erlangen,Erlangen 91054,Germany;Deutsches Zentrum fur Immuntherapie(DYI),Erlangen 91054,Germany;Department of Rheumatology and Clinical Immunology,Faculty of Medicine,Medical Center-University of Freiburg,Freiburg 79106,Germany;Department of Internal Medicine 4,Friedrich-Alexander-University Erlangen-Nurnberg(FAU)and Universit?tsklinikum Erlangen,Erlangen 91054,Germany
文献出处：
引用格式：
[1]Xianyi Meng;Zhen Lin;Shan Cao;Iga Janowska;Koshiro Sonomoto;Darja Andreev;Knab Katharina;Jinming Wen;Karl Xaver Knaup;Michael Sean Wiesener;Gerhard Kr?nke;Marta Rizzi;Georg Schett;Aline Bozec-.Estrogen-mediated downregulation of HIF-1α signaling in B lymphocytes influences postmenopausal bone loss)[J].骨研究（英文版）,2022(02):326-337
A类：
resorbing,colocalize,geranylgeranylacetone
B类：
Estrogen,mediated,downregulation,signaling,lymphocytes,influences,postmenopausal,bone,loss,marrow,cells,osteoclasts,specific,microenvironment,How,functionally,architecture,poorly,understood,Using,genetically,modified,mice,high,throughput,analyses,we,demonstrate,that,prolonged,leads,enhanced,RANKL,production,formation,addition,deletion,prevents,estrogen,deficiency,induced,Mechanistically,controls,protein,stabilization,HSP70,degradation,deficient,promotes,osteoclastogenesis,Induction,expression,by,GGA,administration,alleviates,ovariectomy,osteoporosis,Moreover,has,positive,correlation,HIF1A,human,conclusion,crucial,axis,may,serve,new,therapeutic,target
AB值：
0.530116
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