Hypoxia-inducible factor-1α restricts the anabolic actions of parathyroid hormone.
Hypoxia-inducible factor-1α restricts the anabolic actions of parathyroid hormone.
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DOI：
10.1038/boneres.2014.5
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发表时间：
2014
期刊：
影响因子：
12.7
通讯作者：
Riddle, Ryan C.
中科院分区：
文献类型：
--
作者：
Frey, Julie L.;Stonko, David P.;Faugere, Marie-Claude;Riddle, Ryan C.
The hypoxia inducible factors (Hifs) are evolutionarily conserved transcriptional factors that control homeostatic responses to low oxygen. In developing bone, Hif-1 generated signals induce angiogenesis necessary for osteoblast specification, but in mature bone, loss of Hif-1 in osteoblasts resulted in a more rapid accumulation of bone. These findings suggested that Hif-1 exerts distinct developmental functions and acts as a negative regulator of bone formation. To investigate the function of Hif-1α in osteoanabolic signaling, we assessed the effect of Hif-1α loss-of-function on bone formation in response to intermittent parathyroid hormone (PTH). Mice lacking Hif-1α in osteoblasts and osteocytes form more bone in response to PTH, likely through a larger increase in osteoblast activity and increased sensitivity to the hormone. Consistent with this effect, exposure of primary mouse osteoblasts to PTH resulted in the rapid induction of Hif-1α protein levels via a post-transcriptional mechanism. The enhanced anabolic response appears to result from the removal of Hif-1α-mediated suppression of β-catenin transcriptional activity. Together, these data indicate that Hif-1α functions in the mature skeleton to restrict osteoanabolic signaling. The availability of pharmacological agents that reduce Hif-1α function suggests the value in further exploration of this pathway to optimize the therapeutic benefits of PTH.
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影响因子：
4.8
作者：
Dobnig, H;Turner, RT
通讯作者：
Turner, RT
影响因子：
4.2
作者：
Childress, Paul;Philip, Binu K.;Bidwell, Joseph P.
通讯作者：
Bidwell, Joseph P.
影响因子：
15.9
作者：
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通讯作者：
Manolagas, SC
DOI：
10.1073/pnas.0909353106
发表时间：
2009-10-20
影响因子：
11.1
作者：
Lee, KangAe;Zhang, Huafeng;Semenza, Gregg L.
通讯作者：
Semenza, Gregg L.
影响因子：
4.8
作者：
Akeno, N;Robins, J;Clemens, TL
通讯作者：
Clemens, TL