Mice Lacking DKK1 in T cells Exhibit High Bone Mass and Are Protected from Estrogen-deficiency-induced Bone Loss

Overview

Journal iScience

Publisher Cell Press

Date 2021 Mar 22

PMID 33748710

Citations 10

Authors

Juliane Lehmann

Sylvia Thiele

Ulrike Baschant

Tilman D Rachner

Christof Niehrs

Lorenz C Hofbauer

Martina Rauner

Affiliations

Soon will be listed here.

Abstract

The Wnt inhibitor Dickkopf-1 (DKK1) is a negative regulator of bone formation and bone mass and is dysregulated in various bone diseases. How DKK1 contributes to postmenopausal osteoporosis, however, remains poorly understood. Here, we show that mice lacking DKK1 in T cells are protected from ovariectomy-induced bone loss. Ovariectomy activated CD4+ and CD8+ T cells and increased their production of DKK1. Co-culture of activated T cells with osteoblasts inhibited Wnt signaling in osteoblasts, leading to impaired differentiation. Importantly, DKK1 expression in T cells also controlled physiological bone remodeling. T-cell-deficient knock-out mice had a higher bone mass with an increased bone formation rate and decreased numbers of osteoclasts compared with controls, a phenotype that was rescued by adoptive transfer of wild-type T cells. Thus, these findings highlight that T cells control bone remodeling in health and disease via their expression of DKK1.

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