SIKs control osteocyte responses to parathyroid hormone

Parathyroid hormone (PTH) is an endogenous hormone and osteoporosis therapeutic that suppresses sclerostin activity. Here the authors develop SIK inhibitors as potential therapeutic tools and use them to show that PTH-cAMP signalling in osteocytes inhibits SIK2 from driving Hdac4/5 nuclear shuttling...

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Main Authors: Marc N. Wein, Yanke Liang, Olga Goransson, Thomas B. Sundberg, Jinhua Wang, Elizabeth A. Williams, Maureen J. O’Meara, Nicolas Govea, Belinda Beqo, Shigeki Nishimori, Kenichi Nagano, Daniel J. Brooks, Janaina S. Martins, Braden Corbin, Anthony Anselmo, Ruslan Sadreyev, Joy Y. Wu, Kei Sakamoto, Marc Foretz, Ramnik J. Xavier, Roland Baron, Mary L. Bouxsein, Thomas J. Gardella, Paola Divieti-Pajevic, Nathanael S. Gray, Henry M. Kronenberg
Format: Article
Language:English
Published: Nature Portfolio 2016-10-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/ncomms13176
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author Marc N. Wein
Yanke Liang
Olga Goransson
Thomas B. Sundberg
Jinhua Wang
Elizabeth A. Williams
Maureen J. O’Meara
Nicolas Govea
Belinda Beqo
Shigeki Nishimori
Kenichi Nagano
Daniel J. Brooks
Janaina S. Martins
Braden Corbin
Anthony Anselmo
Ruslan Sadreyev
Joy Y. Wu
Kei Sakamoto
Marc Foretz
Ramnik J. Xavier
Roland Baron
Mary L. Bouxsein
Thomas J. Gardella
Paola Divieti-Pajevic
Nathanael S. Gray
Henry M. Kronenberg
author_facet Marc N. Wein
Yanke Liang
Olga Goransson
Thomas B. Sundberg
Jinhua Wang
Elizabeth A. Williams
Maureen J. O’Meara
Nicolas Govea
Belinda Beqo
Shigeki Nishimori
Kenichi Nagano
Daniel J. Brooks
Janaina S. Martins
Braden Corbin
Anthony Anselmo
Ruslan Sadreyev
Joy Y. Wu
Kei Sakamoto
Marc Foretz
Ramnik J. Xavier
Roland Baron
Mary L. Bouxsein
Thomas J. Gardella
Paola Divieti-Pajevic
Nathanael S. Gray
Henry M. Kronenberg
author_sort Marc N. Wein
collection DOAJ
description Parathyroid hormone (PTH) is an endogenous hormone and osteoporosis therapeutic that suppresses sclerostin activity. Here the authors develop SIK inhibitors as potential therapeutic tools and use them to show that PTH-cAMP signalling in osteocytes inhibits SIK2 from driving Hdac4/5 nuclear shuttling to suppress sclerostin.
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spelling doaj.art-0cde2d55d46f474080f0807c4fb646c22022-12-21T20:39:00ZengNature PortfolioNature Communications2041-17232016-10-017111910.1038/ncomms13176SIKs control osteocyte responses to parathyroid hormoneMarc N. Wein0Yanke Liang1Olga Goransson2Thomas B. Sundberg3Jinhua Wang4Elizabeth A. Williams5Maureen J. O’Meara6Nicolas Govea7Belinda Beqo8Shigeki Nishimori9Kenichi Nagano10Daniel J. Brooks11Janaina S. Martins12Braden Corbin13Anthony Anselmo14Ruslan Sadreyev15Joy Y. Wu16Kei Sakamoto17Marc Foretz18Ramnik J. Xavier19Roland Baron20Mary L. Bouxsein21Thomas J. Gardella22Paola Divieti-Pajevic23Nathanael S. Gray24Henry M. Kronenberg25Department of Medicine, Endocrine Unit, Massachusetts General Hospital, Harvard Medical SchoolDepartment of Biologic Chemistry and Molecular Pharmacology, Dana Farber Cancer Institute, Harvard Medical SchoolDepartment of Experimental Medical Sciences, Lund UniversityCenter for the Development of Therapeutics, Broad InstituteDepartment of Biologic Chemistry and Molecular Pharmacology, Dana Farber Cancer Institute, Harvard Medical SchoolDepartment of Medicine, Endocrine Unit, Massachusetts General Hospital, Harvard Medical SchoolDepartment of Medicine, Endocrine Unit, Massachusetts General Hospital, Harvard Medical SchoolDepartment of Medicine, Endocrine Unit, Massachusetts General Hospital, Harvard Medical SchoolDepartment of Medicine, Endocrine Unit, Massachusetts General Hospital, Harvard Medical SchoolDepartment of Medicine, Endocrine Unit, Massachusetts General Hospital, Harvard Medical SchoolDepartment of Oral Medicine, Harvard School of Dental Medicine, Infection, and Immunity, 188 Longwood Avenue, Boston, Massachusetts 02115, USDepartment of Medicine, Endocrine Unit, Massachusetts General Hospital, Harvard Medical SchoolDepartment of Medicine, Endocrine Unit, Massachusetts General Hospital, Harvard Medical SchoolDepartment of Medicine, Endocrine Unit, Massachusetts General Hospital, Harvard Medical SchoolDepartment of Molecular Biology, Massachusetts General Hospital, Harvard Medical SchoolDepartment of Molecular Biology, Massachusetts General Hospital, Harvard Medical SchoolDivision of Endocrinology, Department of Medicine, Stanford University School of MedicineMRC Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of DundeeINSERM U1016, Institut Cochin, CNRS UMR8104, Universite Paris Descartes Sorbonne Pairs CiteDepartment of Medicine, Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General HospitalDepartment of Medicine, Endocrine Unit, Massachusetts General Hospital, Harvard Medical SchoolDepartment of Medicine, Endocrine Unit, Massachusetts General Hospital, Harvard Medical SchoolDepartment of Medicine, Endocrine Unit, Massachusetts General Hospital, Harvard Medical SchoolHenry M. Goldman School of Dental Medicine, Boston UniversityDepartment of Biologic Chemistry and Molecular Pharmacology, Dana Farber Cancer Institute, Harvard Medical SchoolDepartment of Medicine, Endocrine Unit, Massachusetts General Hospital, Harvard Medical SchoolParathyroid hormone (PTH) is an endogenous hormone and osteoporosis therapeutic that suppresses sclerostin activity. Here the authors develop SIK inhibitors as potential therapeutic tools and use them to show that PTH-cAMP signalling in osteocytes inhibits SIK2 from driving Hdac4/5 nuclear shuttling to suppress sclerostin.https://doi.org/10.1038/ncomms13176
spellingShingle Marc N. Wein
Yanke Liang
Olga Goransson
Thomas B. Sundberg
Jinhua Wang
Elizabeth A. Williams
Maureen J. O’Meara
Nicolas Govea
Belinda Beqo
Shigeki Nishimori
Kenichi Nagano
Daniel J. Brooks
Janaina S. Martins
Braden Corbin
Anthony Anselmo
Ruslan Sadreyev
Joy Y. Wu
Kei Sakamoto
Marc Foretz
Ramnik J. Xavier
Roland Baron
Mary L. Bouxsein
Thomas J. Gardella
Paola Divieti-Pajevic
Nathanael S. Gray
Henry M. Kronenberg
SIKs control osteocyte responses to parathyroid hormone
Nature Communications
title SIKs control osteocyte responses to parathyroid hormone
title_full SIKs control osteocyte responses to parathyroid hormone
title_fullStr SIKs control osteocyte responses to parathyroid hormone
title_full_unstemmed SIKs control osteocyte responses to parathyroid hormone
title_short SIKs control osteocyte responses to parathyroid hormone
title_sort siks control osteocyte responses to parathyroid hormone
url https://doi.org/10.1038/ncomms13176
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