SIKs control osteocyte responses to parathyroid hormone

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Standard

SIKs control osteocyte responses to parathyroid hormone. / Wein, Marc N.; Liang, Yanke; Goransson, Olga; Sundberg, Thomas B.; Wang, Jinhua; Williams, Elizabeth A.; O'Meara, Maureen J.; Govea, Nicolas; Beqo, Belinda; Nishimori, Shigeki; Nagano, Kenichi; Brooks, Daniel J.; Martins, Janaina S.; Corbin, Braden; Anselmo, Anthony; Sadreyev, Ruslan; Wu, Joy Y.; Sakamoto, Kei; Foretz, Marc; Xavier, Ramnik J.; Baron, Roland; Bouxsein, Mary L.; Gardella, Thomas J.; Divieti-Pajevic, Paola; Gray, Nathanael S.; Kronenberg, Henry M.

I: Nature Communications, Bind 7, 13176, 19.10.2016.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Wein, MN, Liang, Y, Goransson, O, Sundberg, TB, Wang, J, Williams, EA, O'Meara, MJ, Govea, N, Beqo, B, Nishimori, S, Nagano, K, Brooks, DJ, Martins, JS, Corbin, B, Anselmo, A, Sadreyev, R, Wu, JY, Sakamoto, K, Foretz, M, Xavier, RJ, Baron, R, Bouxsein, ML, Gardella, TJ, Divieti-Pajevic, P, Gray, NS & Kronenberg, HM 2016, 'SIKs control osteocyte responses to parathyroid hormone', Nature Communications, bind 7, 13176. https://doi.org/10.1038/ncomms13176

APA

Wein, M. N., Liang, Y., Goransson, O., Sundberg, T. B., Wang, J., Williams, E. A., O'Meara, M. J., Govea, N., Beqo, B., Nishimori, S., Nagano, K., Brooks, D. J., Martins, J. S., Corbin, B., Anselmo, A., Sadreyev, R., Wu, J. Y., Sakamoto, K., Foretz, M., ... Kronenberg, H. M. (2016). SIKs control osteocyte responses to parathyroid hormone. Nature Communications, 7, [13176]. https://doi.org/10.1038/ncomms13176

Vancouver

Wein MN, Liang Y, Goransson O, Sundberg TB, Wang J, Williams EA o.a. SIKs control osteocyte responses to parathyroid hormone. Nature Communications. 2016 okt. 19;7. 13176. https://doi.org/10.1038/ncomms13176

Author

Wein, Marc N. ; Liang, Yanke ; Goransson, Olga ; Sundberg, Thomas B. ; Wang, Jinhua ; Williams, Elizabeth A. ; O'Meara, Maureen J. ; Govea, Nicolas ; Beqo, Belinda ; Nishimori, Shigeki ; Nagano, Kenichi ; Brooks, Daniel J. ; Martins, Janaina S. ; Corbin, Braden ; Anselmo, Anthony ; Sadreyev, Ruslan ; Wu, Joy Y. ; Sakamoto, Kei ; Foretz, Marc ; Xavier, Ramnik J. ; Baron, Roland ; Bouxsein, Mary L. ; Gardella, Thomas J. ; Divieti-Pajevic, Paola ; Gray, Nathanael S. ; Kronenberg, Henry M. / SIKs control osteocyte responses to parathyroid hormone. I: Nature Communications. 2016 ; Bind 7.

Bibtex

@article{fba5a57c1b934383b93c91430b8ca94c,
title = "SIKs control osteocyte responses to parathyroid hormone",
abstract = "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.",
author = "Wein, {Marc N.} and Yanke Liang and Olga Goransson and Sundberg, {Thomas B.} and Jinhua Wang and Williams, {Elizabeth A.} and O'Meara, {Maureen J.} and Nicolas Govea and Belinda Beqo and Shigeki Nishimori and Kenichi Nagano and Brooks, {Daniel J.} and Martins, {Janaina S.} and Braden Corbin and Anthony Anselmo and Ruslan Sadreyev and Wu, {Joy Y.} and Kei Sakamoto and Marc Foretz and Xavier, {Ramnik J.} and Roland Baron and Bouxsein, {Mary L.} and Gardella, {Thomas J.} and Paola Divieti-Pajevic and Gray, {Nathanael S.} and Kronenberg, {Henry M.}",
year = "2016",
month = oct,
day = "19",
doi = "10.1038/ncomms13176",
language = "English",
volume = "7",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - SIKs control osteocyte responses to parathyroid hormone

AU - Wein, Marc N.

AU - Liang, Yanke

AU - Goransson, Olga

AU - Sundberg, Thomas B.

AU - Wang, Jinhua

AU - Williams, Elizabeth A.

AU - O'Meara, Maureen J.

AU - Govea, Nicolas

AU - Beqo, Belinda

AU - Nishimori, Shigeki

AU - Nagano, Kenichi

AU - Brooks, Daniel J.

AU - Martins, Janaina S.

AU - Corbin, Braden

AU - Anselmo, Anthony

AU - Sadreyev, Ruslan

AU - Wu, Joy Y.

AU - Sakamoto, Kei

AU - Foretz, Marc

AU - Xavier, Ramnik J.

AU - Baron, Roland

AU - Bouxsein, Mary L.

AU - Gardella, Thomas J.

AU - Divieti-Pajevic, Paola

AU - Gray, Nathanael S.

AU - Kronenberg, Henry M.

PY - 2016/10/19

Y1 - 2016/10/19

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84992061004&partnerID=8YFLogxK

U2 - 10.1038/ncomms13176

DO - 10.1038/ncomms13176

M3 - Journal article

C2 - 27759007

AN - SCOPUS:84992061004

VL - 7

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 13176

ER -

ID: 238745182