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WNT16 Requires Gα Subunits as Intracellular Partners for Both Its Canonical and Non-Canonical WNT Signalling Activity in Osteoblasts

Standard

WNT16 Requires Gα Subunits as Intracellular Partners for Both Its Canonical and Non-Canonical WNT Signalling Activity in Osteoblasts. / Hendrickx, Gretl; Boudin, Eveline; Verbeek, Marinus; Fransen, Erik; Mortier, Geert; Van Hul, Wim.

In: CALCIFIED TISSUE INT, Vol. 106, No. 3, 03.2020, p. 294-302.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Hendrickx, G, Boudin, E, Verbeek, M, Fransen, E, Mortier, G & Van Hul, W 2020, 'WNT16 Requires Gα Subunits as Intracellular Partners for Both Its Canonical and Non-Canonical WNT Signalling Activity in Osteoblasts', CALCIFIED TISSUE INT, vol. 106, no. 3, pp. 294-302. https://doi.org/10.1007/s00223-019-00633-x

APA

Hendrickx, G., Boudin, E., Verbeek, M., Fransen, E., Mortier, G., & Van Hul, W. (2020). WNT16 Requires Gα Subunits as Intracellular Partners for Both Its Canonical and Non-Canonical WNT Signalling Activity in Osteoblasts. CALCIFIED TISSUE INT, 106(3), 294-302. https://doi.org/10.1007/s00223-019-00633-x

Vancouver

Hendrickx G, Boudin E, Verbeek M, Fransen E, Mortier G, Van Hul W. WNT16 Requires Gα Subunits as Intracellular Partners for Both Its Canonical and Non-Canonical WNT Signalling Activity in Osteoblasts. CALCIFIED TISSUE INT. 2020 Mar;106(3):294-302. https://doi.org/10.1007/s00223-019-00633-x

Bibtex

@article{ef725547f9ff4adca61194bad70b1a3e,
title = "WNT16 Requires Gα Subunits as Intracellular Partners for Both Its Canonical and Non-Canonical WNT Signalling Activity in Osteoblasts",
abstract = "In the past years, WNT16 became an interesting target in the field of skeletal research, as it was identified as an essential regulator of the cortical bone compartment, with the ability to increase both cortical and trabecular bone mass and strength in vivo. Even though there are indications that these advantageous effects are coming from canonical and non-canonical WNT-signalling activity, a clear model of WNT signalling by WNT16 is not yet depicted. We, therefore, investigated the modulation of canonical (WNT/β-catenin) and non-canonical [WNT/calcium, WNT/planar cell polarity (PCP)] signalling in human embryonic kidney (HEK) 293 T and SaOS2 cells. Here, we demonstrated that WNT16 activates all WNT-signalling pathways in osteoblasts, whereas only WNT/calcium signalling was activated in HEK293T cells. In osteoblasts, we therefore, additionally investigated the role of Gα subunits as intracellular partners in WNT16's mechanism of action by performing knockdown of Gα12, Gα13 and Gαq. These studies point out that the above-mentioned Gα subunits might be involved in the WNT/β-catenin and WNT/calcium-signalling activity by WNT16 in osteoblasts, and for Gα12 in its WNT/PCP-signalling activity, illustrating a novel possible mechanism of interplay between the different WNT-signalling pathways in osteoblasts. Additional studies are needed to demonstrate whether this mechanism is specific for WNT16 signalling or relevant for all other WNT ligands as well. Altogether, we further defined WNT16's mechanism of action in osteoblasts that might underlie the well-known beneficial effects of WNT16 on skeletal homeostasis. These findings on WNT16 and the activity of specific Gα subunits in osteoblasts could definitely contribute to the development of novel therapeutic approaches for fragility fractures in the future.",
author = "Gretl Hendrickx and Eveline Boudin and Marinus Verbeek and Erik Fransen and Geert Mortier and {Van Hul}, Wim",
year = "2020",
month = mar,
doi = "10.1007/s00223-019-00633-x",
language = "English",
volume = "106",
pages = "294--302",
journal = "CALCIFIED TISSUE INT",
issn = "0171-967X",
publisher = "Springer New York",
number = "3",

}

RIS

TY - JOUR

T1 - WNT16 Requires Gα Subunits as Intracellular Partners for Both Its Canonical and Non-Canonical WNT Signalling Activity in Osteoblasts

AU - Hendrickx, Gretl

AU - Boudin, Eveline

AU - Verbeek, Marinus

AU - Fransen, Erik

AU - Mortier, Geert

AU - Van Hul, Wim

PY - 2020/3

Y1 - 2020/3

N2 - In the past years, WNT16 became an interesting target in the field of skeletal research, as it was identified as an essential regulator of the cortical bone compartment, with the ability to increase both cortical and trabecular bone mass and strength in vivo. Even though there are indications that these advantageous effects are coming from canonical and non-canonical WNT-signalling activity, a clear model of WNT signalling by WNT16 is not yet depicted. We, therefore, investigated the modulation of canonical (WNT/β-catenin) and non-canonical [WNT/calcium, WNT/planar cell polarity (PCP)] signalling in human embryonic kidney (HEK) 293 T and SaOS2 cells. Here, we demonstrated that WNT16 activates all WNT-signalling pathways in osteoblasts, whereas only WNT/calcium signalling was activated in HEK293T cells. In osteoblasts, we therefore, additionally investigated the role of Gα subunits as intracellular partners in WNT16's mechanism of action by performing knockdown of Gα12, Gα13 and Gαq. These studies point out that the above-mentioned Gα subunits might be involved in the WNT/β-catenin and WNT/calcium-signalling activity by WNT16 in osteoblasts, and for Gα12 in its WNT/PCP-signalling activity, illustrating a novel possible mechanism of interplay between the different WNT-signalling pathways in osteoblasts. Additional studies are needed to demonstrate whether this mechanism is specific for WNT16 signalling or relevant for all other WNT ligands as well. Altogether, we further defined WNT16's mechanism of action in osteoblasts that might underlie the well-known beneficial effects of WNT16 on skeletal homeostasis. These findings on WNT16 and the activity of specific Gα subunits in osteoblasts could definitely contribute to the development of novel therapeutic approaches for fragility fractures in the future.

AB - In the past years, WNT16 became an interesting target in the field of skeletal research, as it was identified as an essential regulator of the cortical bone compartment, with the ability to increase both cortical and trabecular bone mass and strength in vivo. Even though there are indications that these advantageous effects are coming from canonical and non-canonical WNT-signalling activity, a clear model of WNT signalling by WNT16 is not yet depicted. We, therefore, investigated the modulation of canonical (WNT/β-catenin) and non-canonical [WNT/calcium, WNT/planar cell polarity (PCP)] signalling in human embryonic kidney (HEK) 293 T and SaOS2 cells. Here, we demonstrated that WNT16 activates all WNT-signalling pathways in osteoblasts, whereas only WNT/calcium signalling was activated in HEK293T cells. In osteoblasts, we therefore, additionally investigated the role of Gα subunits as intracellular partners in WNT16's mechanism of action by performing knockdown of Gα12, Gα13 and Gαq. These studies point out that the above-mentioned Gα subunits might be involved in the WNT/β-catenin and WNT/calcium-signalling activity by WNT16 in osteoblasts, and for Gα12 in its WNT/PCP-signalling activity, illustrating a novel possible mechanism of interplay between the different WNT-signalling pathways in osteoblasts. Additional studies are needed to demonstrate whether this mechanism is specific for WNT16 signalling or relevant for all other WNT ligands as well. Altogether, we further defined WNT16's mechanism of action in osteoblasts that might underlie the well-known beneficial effects of WNT16 on skeletal homeostasis. These findings on WNT16 and the activity of specific Gα subunits in osteoblasts could definitely contribute to the development of novel therapeutic approaches for fragility fractures in the future.

U2 - 10.1007/s00223-019-00633-x

DO - 10.1007/s00223-019-00633-x

M3 - SCORING: Journal article

C2 - 31760436

VL - 106

SP - 294

EP - 302

JO - CALCIFIED TISSUE INT

JF - CALCIFIED TISSUE INT

SN - 0171-967X

IS - 3

ER -