T Lymphocytes Amplify the Anabolic Activity of Parathyroid Hormone through Wnt10b Signaling

Masakazu Terauchi; Jau Yi Li; Brahmchetna Bedi; Ki Hyun Baek; Hesham Tawfeek; Sarah Galley; Linda Gilbert; Mark S. Nanes; Majd Zayzafoon; Robert Guldberg; David L. Lamar; Meredith A. Singer; Timothy F Lane; Henry M. Kronenberg; M. Neale Weitzmann; Roberto Pacifici

doi:10.1016/j.cmet.2009.07.010

T Lymphocytes Amplify the Anabolic Activity of Parathyroid Hormone through Wnt10b Signaling

Masakazu Terauchi, Jau Yi Li, Brahmchetna Bedi, Ki Hyun Baek, Hesham Tawfeek, Sarah Galley, Linda Gilbert, Mark S. Nanes, Majd Zayzafoon, Robert Guldberg, David L. Lamar, Meredith A. Singer, Timothy F Lane, Henry M. Kronenberg, M. Neale Weitzmann, Roberto Pacifici^*

^*Corresponding author for this work

Medical Education

Research output: Contribution to journal › Article › peer-review

149 Scopus citations

Abstract

Intermittent administration of parathyroid hormone (iPTH) is used to treat osteoporosis because it improves bone architecture and strength, but the underlying cellular and molecular mechanisms are unclear. Here, we show that iPTH increases the production of Wnt10b by bone marrow CD8+ T cells and induces these lymphocytes to activate canonical Wnt signaling in preosteoblasts. Accordingly, in responses to iPTH, T cell null mice display diminished Wnt signaling in preosteoblasts and blunted osteoblastic commitment, proliferation, differentiation, and life span, which result in decreased trabecular bone anabolism and no increase in strength. Demonstrating the specific role of lymphocytic Wnt10b, iPTH has no anabolic activity in mice lacking T-cell-produced Wnt10b. Therefore, T-cell-mediated activation of Wnt signaling in osteoblastic cells plays a key permissive role in the mechanism by which iPTH increases bone strength, suggesting that T cell osteoblast crosstalk pathways may provide pharmacological targets for bone anabolism.

Original language	English (US)
Pages (from-to)	229-240
Number of pages	12
Journal	Cell Metabolism
Volume	10
Issue number	3
DOIs	https://doi.org/10.1016/j.cmet.2009.07.010
State	Published - Sep 2 2009

Keywords

HUMDISEASE

ASJC Scopus subject areas

Physiology
Molecular Biology
Cell Biology

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10.1016/j.cmet.2009.07.010

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Terauchi, M., Li, J. Y., Bedi, B., Baek, K. H., Tawfeek, H., Galley, S., Gilbert, L., Nanes, M. S., Zayzafoon, M., Guldberg, R., Lamar, D. L., Singer, M. A., Lane, T. F., Kronenberg, H. M., Weitzmann, M. N., & Pacifici, R. (2009). T Lymphocytes Amplify the Anabolic Activity of Parathyroid Hormone through Wnt10b Signaling. Cell Metabolism, 10(3), 229-240. https://doi.org/10.1016/j.cmet.2009.07.010

@article{adc6c1d2ab6e45e1b8e29a6ae48618fd,

title = "T Lymphocytes Amplify the Anabolic Activity of Parathyroid Hormone through Wnt10b Signaling",

abstract = "Intermittent administration of parathyroid hormone (iPTH) is used to treat osteoporosis because it improves bone architecture and strength, but the underlying cellular and molecular mechanisms are unclear. Here, we show that iPTH increases the production of Wnt10b by bone marrow CD8+ T cells and induces these lymphocytes to activate canonical Wnt signaling in preosteoblasts. Accordingly, in responses to iPTH, T cell null mice display diminished Wnt signaling in preosteoblasts and blunted osteoblastic commitment, proliferation, differentiation, and life span, which result in decreased trabecular bone anabolism and no increase in strength. Demonstrating the specific role of lymphocytic Wnt10b, iPTH has no anabolic activity in mice lacking T-cell-produced Wnt10b. Therefore, T-cell-mediated activation of Wnt signaling in osteoblastic cells plays a key permissive role in the mechanism by which iPTH increases bone strength, suggesting that T cell osteoblast crosstalk pathways may provide pharmacological targets for bone anabolism.",

keywords = "HUMDISEASE",

author = "Masakazu Terauchi and Li, {Jau Yi} and Brahmchetna Bedi and Baek, {Ki Hyun} and Hesham Tawfeek and Sarah Galley and Linda Gilbert and Nanes, {Mark S.} and Majd Zayzafoon and Robert Guldberg and Lamar, {David L.} and Singer, {Meredith A.} and Lane, {Timothy F} and Kronenberg, {Henry M.} and Weitzmann, {M. Neale} and Roberto Pacifici",

note = "Funding Information: This study was supported by grants from the National Institutes of Health (AR54625 and AG28278). We are grateful to Laurie McCauley (University of Michigan) for her review of the manuscript. ",

year = "2009",

month = sep,

day = "2",

doi = "10.1016/j.cmet.2009.07.010",

language = "English (US)",

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Terauchi, M, Li, JY, Bedi, B, Baek, KH, Tawfeek, H, Galley, S, Gilbert, L, Nanes, MS, Zayzafoon, M, Guldberg, R, Lamar, DL, Singer, MA, Lane, TF, Kronenberg, HM, Weitzmann, MN & Pacifici, R 2009, 'T Lymphocytes Amplify the Anabolic Activity of Parathyroid Hormone through Wnt10b Signaling', Cell Metabolism, vol. 10, no. 3, pp. 229-240. https://doi.org/10.1016/j.cmet.2009.07.010

TY - JOUR

T1 - T Lymphocytes Amplify the Anabolic Activity of Parathyroid Hormone through Wnt10b Signaling

AU - Terauchi, Masakazu

AU - Li, Jau Yi

AU - Bedi, Brahmchetna

AU - Baek, Ki Hyun

AU - Tawfeek, Hesham

AU - Galley, Sarah

AU - Gilbert, Linda

AU - Nanes, Mark S.

AU - Zayzafoon, Majd

AU - Guldberg, Robert

AU - Lamar, David L.

AU - Singer, Meredith A.

AU - Lane, Timothy F

AU - Kronenberg, Henry M.

AU - Weitzmann, M. Neale

AU - Pacifici, Roberto

N1 - Funding Information: This study was supported by grants from the National Institutes of Health (AR54625 and AG28278). We are grateful to Laurie McCauley (University of Michigan) for her review of the manuscript.

PY - 2009/9/2

Y1 - 2009/9/2

N2 - Intermittent administration of parathyroid hormone (iPTH) is used to treat osteoporosis because it improves bone architecture and strength, but the underlying cellular and molecular mechanisms are unclear. Here, we show that iPTH increases the production of Wnt10b by bone marrow CD8+ T cells and induces these lymphocytes to activate canonical Wnt signaling in preosteoblasts. Accordingly, in responses to iPTH, T cell null mice display diminished Wnt signaling in preosteoblasts and blunted osteoblastic commitment, proliferation, differentiation, and life span, which result in decreased trabecular bone anabolism and no increase in strength. Demonstrating the specific role of lymphocytic Wnt10b, iPTH has no anabolic activity in mice lacking T-cell-produced Wnt10b. Therefore, T-cell-mediated activation of Wnt signaling in osteoblastic cells plays a key permissive role in the mechanism by which iPTH increases bone strength, suggesting that T cell osteoblast crosstalk pathways may provide pharmacological targets for bone anabolism.

AB - Intermittent administration of parathyroid hormone (iPTH) is used to treat osteoporosis because it improves bone architecture and strength, but the underlying cellular and molecular mechanisms are unclear. Here, we show that iPTH increases the production of Wnt10b by bone marrow CD8+ T cells and induces these lymphocytes to activate canonical Wnt signaling in preosteoblasts. Accordingly, in responses to iPTH, T cell null mice display diminished Wnt signaling in preosteoblasts and blunted osteoblastic commitment, proliferation, differentiation, and life span, which result in decreased trabecular bone anabolism and no increase in strength. Demonstrating the specific role of lymphocytic Wnt10b, iPTH has no anabolic activity in mice lacking T-cell-produced Wnt10b. Therefore, T-cell-mediated activation of Wnt signaling in osteoblastic cells plays a key permissive role in the mechanism by which iPTH increases bone strength, suggesting that T cell osteoblast crosstalk pathways may provide pharmacological targets for bone anabolism.

KW - HUMDISEASE

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U2 - 10.1016/j.cmet.2009.07.010

DO - 10.1016/j.cmet.2009.07.010

M3 - Article

C2 - 19723499

AN - SCOPUS:69149106680

SN - 1550-4131

VL - 10

SP - 229

EP - 240

JO - Cell Metabolism

JF - Cell Metabolism

IS - 3

ER -

T Lymphocytes Amplify the Anabolic Activity of Parathyroid Hormone through Wnt10b Signaling

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