Your browser doesn't support javascript.
loading
Mice lacking DKK1 in T cells exhibit high bone mass and are protected from estrogen-deficiency-induced bone loss.
Lehmann, Juliane; Thiele, Sylvia; Baschant, Ulrike; Rachner, Tilman D; Niehrs, Christof; Hofbauer, Lorenz C; Rauner, Martina.
Afiliação
  • Lehmann J; Department of Medicine III, Division of Endocrinology, Diabetes and Bone Diseases, Technische Universität Dresden, Dresden 01307, Germany.
  • Thiele S; Center for Healthy Aging, Technische Universität Dresden, Dresden, Germany.
  • Baschant U; Department of Medicine III, Division of Endocrinology, Diabetes and Bone Diseases, Technische Universität Dresden, Dresden 01307, Germany.
  • Rachner TD; Center for Healthy Aging, Technische Universität Dresden, Dresden, Germany.
  • Niehrs C; Department of Medicine III, Division of Endocrinology, Diabetes and Bone Diseases, Technische Universität Dresden, Dresden 01307, Germany.
  • Hofbauer LC; Center for Healthy Aging, Technische Universität Dresden, Dresden, Germany.
  • Rauner M; Department of Medicine III, Division of Endocrinology, Diabetes and Bone Diseases, Technische Universität Dresden, Dresden 01307, Germany.
iScience ; 24(3): 102224, 2021 Mar 19.
Article em En | MEDLINE | ID: mdl-33748710
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 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.
Palavras-chave

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2021 Tipo de documento: Article