Mice lacking DKK1 in T cells exhibit high bone mass and are protected from estrogen-deficiency-induced bone loss
Juliane Lehmann,
Sylvia Thiele,
Ulrike Baschant,
Tilman D. Rachner,
Christof Niehrs,
Lorenz C. Hofbauer,
Martina Rauner
Affiliations
Juliane Lehmann
Department of Medicine III, Division of Endocrinology, Diabetes and Bone Diseases, Technische Universität Dresden, Dresden 01307, Germany; Center for Healthy Aging, Technische Universität Dresden, Dresden, Germany
Sylvia Thiele
Department of Medicine III, Division of Endocrinology, Diabetes and Bone Diseases, Technische Universität Dresden, Dresden 01307, Germany; Center for Healthy Aging, Technische Universität Dresden, Dresden, Germany
Ulrike Baschant
Department of Medicine III, Division of Endocrinology, Diabetes and Bone Diseases, Technische Universität Dresden, Dresden 01307, Germany; Center for Healthy Aging, Technische Universität Dresden, Dresden, Germany
Tilman D. Rachner
Department of Medicine III, Division of Endocrinology, Diabetes and Bone Diseases, Technische Universität Dresden, Dresden 01307, Germany; Center for Healthy Aging, Technische Universität Dresden, Dresden, Germany
Christof Niehrs
Division of Molecular Embryology, DKFZ-ZMBH Alliance, Heidelberg, Germany; Institute of Molecular Biology, Mainz, Germany
Lorenz C. Hofbauer
Department of Medicine III, Division of Endocrinology, Diabetes and Bone Diseases, Technische Universität Dresden, Dresden 01307, Germany; Center for Regenerative Therapies Dresden, Technische Universität Dresden, Dresden, Germany
Martina Rauner
Department of Medicine III, Division of Endocrinology, Diabetes and Bone Diseases, Technische Universität Dresden, Dresden 01307, Germany; Center for Healthy Aging, Technische Universität Dresden, Dresden, Germany; Corresponding author
Summary: 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 Dkk1 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.
