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

被引：68

作者：

Bedi, Brahmchetna ^{[1
,2
]}

Li, Jau-Yi ^{[1
]}

Tawfeek, Hesham ^{[1
]}

Baek, Ki-Hyun ^{[1
]}

Adams, Jonathan ^{[1
]}

Vangara, Sameera S. ^{[1
]}

Chang, Ming-Kang ^{[3
]}

Kneissel, Michaela ^{[3
]}

Weitzmanna, M. Neale ^{[1
,2
]}

Pacifici, Roberto ^{[1
,4
]}

机构：

[1] Emory Univ, Dept Med, Div Endocrinol Metab & Lipids, Atlanta, GA 30322 USA

[2] Atlanta Vet Affairs Med Ctr, Decatur, GA 30033 USA

[3] Novartis Inst Biomed Res, CH-4002 Basel, Switzerland

[4] Emory Univ, Immunol & Mol Pathogenesis Program, Atlanta, GA 30322 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2012年 / 109卷 / 12期

基金：

美国国家卫生研究院;

关键词：

bone mass; T lymphocytes; bone cells; MESENCHYMAL STEM-CELLS; BETA-CATENIN; DIFFERENTIATED OSTEOBLASTS; TUBEROINFUNDIBULAR PEPTIDE; POSTMENOPAUSAL WOMEN; OSTEOCLAST FORMATION; GENE-EXPRESSION; CD40; LIGAND; IN-VIVO; WNT;

D O I：

10.1073/pnas.1120735109

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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.

引用

页码：E725 / E733

页数：9

共 58 条

[1]

CD40 ligand blocks apoptosis induced by tumor necrosis factor α, glucocorticoids, and etoposide in osteoblasts and the osteocyte-like cell line murine long bone osteocyte-Y4 [J].