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Silencing of parathyroid hormone (PTH) receptor 1 in T cells blunts the bone anabolic activity of PTH.


ABSTRACT: Intermittent parathyroid hormone (iPTH) treatment stimulates T-cell production of the osteogenic Wnt ligand Wnt10b, a factor required for iPTH to activate Wnt signaling in osteoblasts and stimulate bone formation. However, it is unknown whether iPTH induces Wnt10b production and bone anabolism through direct activation of the parathyroid hormone (PTH)/PTH-related protein receptor (PPR) in T cells. Here, we show that conditional silencing of PPR in T cells blunts the capacity of iPTH to induce T-cell production of Wnt10b; activate Wnt signaling in osteoblasts; expand the osteoblastic pool; and increase bone turnover, bone mineral density, and trabecular bone volume. These findings demonstrate that direct PPR signaling in T cells plays an important role in PTH-induced bone anabolism by promoting T-cell production of Wnt10b and suggest that T cells may provide pharmacological targets for bone anabolism.

SUBMITTER: Bedi B 

PROVIDER: S-EPMC3311391 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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Silencing of parathyroid hormone (PTH) receptor 1 in T cells blunts the bone anabolic activity of PTH.

Bedi Brahmchetna B   Li Jau-Yi JY   Tawfeek Hesham H   Baek Ki-Hyun KH   Adams Jonathan J   Vangara Sameera S SS   Chang Ming-Kang MK   Kneissel Michaela M   Weitzmann M Neale MN   Pacifici Roberto R  

Proceedings of the National Academy of Sciences of the United States of America 20120305 12


Intermittent parathyroid hormone (iPTH) treatment stimulates T-cell production of the osteogenic Wnt ligand Wnt10b, a factor required for iPTH to activate Wnt signaling in osteoblasts and stimulate bone formation. However, it is unknown whether iPTH induces Wnt10b production and bone anabolism through direct activation of the parathyroid hormone (PTH)/PTH-related protein receptor (PPR) in T cells. Here, we show that conditional silencing of PPR in T cells blunts the capacity of iPTH to induce T-  ...[more]

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