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SIKs control osteoc...
SIKs control osteocyte responses to parathyroid hormone
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- Wein, Marc N. (author)
- Harvard University,Massachusetts General Hospital
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- Liang, Yanke (author)
- Harvard University
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- Göransson, Olga (author)
- Lund University,Lunds universitet,Proteinfosforylering,Forskargrupper vid Lunds universitet,Protein Phosphorylation,Lund University Research Groups
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- Sundberg, Thomas B. (author)
- Helsinki University Central Hospital,Broad Institute
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- Wang, Jinhua (author)
- Harvard University
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- Williams, Elizabeth A. (author)
- Massachusetts General Hospital,Harvard University
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- O'Meara, Maureen J. (author)
- Massachusetts General Hospital,Harvard University
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- Govea, Nicolas (author)
- Harvard University,Massachusetts General Hospital
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- Beqo, Belinda (author)
- Harvard University,Massachusetts General Hospital
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- Nishimori, Shigeki (author)
- Massachusetts General Hospital,Harvard University
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- Nagano, Kenichi (author)
- Harvard University
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- Brooks, Daniel J. (author)
- Beth Israel Deaconess Medical Center,Harvard University
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- Martins, Janaina S. (author)
- Harvard University,Massachusetts General Hospital
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- Corbin, Braden (author)
- Massachusetts General Hospital,Harvard University
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- Anselmo, Anthony (author)
- Harvard University,Massachusetts General Hospital
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- Sadreyev, Ruslan (author)
- Massachusetts General Hospital
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- Wu, Joy Y. (author)
- Stanford University
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- Sakamoto, Kei (author)
- University of Dundee
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- Foretz, Marc (author)
- Paris Descartes University
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- Xavier, Ramnik J. (author)
- Massachusetts General Hospital,Harvard University,Broad Institute
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- Baron, Roland (author)
- Harvard University,Massachusetts General Hospital
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- Bouxsein, Mary L. (author)
- Beth Israel Deaconess Medical Center,Harvard University
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- Gardella, Thomas J. (author)
- Massachusetts General Hospital,Harvard University
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- Divieti-Pajevic, Paola (author)
- Boston University
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- Gray, Nathanael S. (author)
- Harvard University
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- Kronenberg, Henry M. (author)
- Harvard University,Massachusetts General Hospital
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(creator_code:org_t)
- 2016-10-19
- 2016
- English.
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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https://doi.org/10.1...
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Abstract
Subject headings
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- Parathyroid hormone (PTH) activates receptors on osteocytes to orchestrate bone formation and resorption. Here we show that PTH inhibition of SOST (sclerostin), a WNT antagonist, requires HDAC4 and HDAC5, whereas PTH stimulation of RANKL, a stimulator of bone resorption, requires CRTC2. Salt inducible kinases (SIKs) control subcellular localization of HDAC4/5 and CRTC2. PTH regulates both HDAC4/5 and CRTC2 localization via phosphorylation and inhibition of SIK2. Like PTH, new small molecule SIK inhibitors cause decreased phosphorylation and increased nuclear translocation of HDAC4/5 and CRTC2. SIK inhibition mimics many of the effects of PTH in osteocytes as assessed by RNA-seq in cultured osteocytes and following in vivo administration. Once daily treatment with the small molecule SIK inhibitor YKL-05-099 increases bone formation and bone mass. Therefore, a major arm of PTH signalling in osteocytes involves SIK inhibition, and small molecule SIK inhibitors may be applied therapeutically to mimic skeletal effects of PTH.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
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- art (subject category)
- ref (subject category)
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- By the author/editor
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Wein, Marc N.
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Liang, Yanke
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Göransson, Olga
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Sundberg, Thomas ...
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Wang, Jinhua
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Williams, Elizab ...
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show more...
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O'Meara, Maureen ...
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Govea, Nicolas
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Beqo, Belinda
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Nishimori, Shige ...
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Nagano, Kenichi
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Brooks, Daniel J ...
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Martins, Janaina ...
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Corbin, Braden
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Anselmo, Anthony
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Sadreyev, Ruslan
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Wu, Joy Y.
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Sakamoto, Kei
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Foretz, Marc
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Xavier, Ramnik J ...
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Baron, Roland
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Bouxsein, Mary L ...
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Gardella, Thomas ...
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Divieti-Pajevic, ...
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Gray, Nathanael ...
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Kronenberg, Henr ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
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Nature Communica ...
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Lund University