Increased bone density and resistance to ovariectomy-induced bone loss in FoxP3-transgenic mice based on impaired osteoclast differentiation
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Increased bone density and resistance to ovariectomy-induced bone loss in FoxP3-transgenic mice based on impaired osteoclast differentiation. / Zaiss, Mario M; Sarter, Kerstin; Hess, Andreas; Engelke, Klaus; Böhm, Christina; Nimmerjahn, Falk; Voll, Reinhard; Schett, Georg; David, Jean-Pierre.
in: ARTHRITIS RHEUMATOL, Jahrgang 62, Nr. 8, 01.08.2010, S. 2328-38.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Increased bone density and resistance to ovariectomy-induced bone loss in FoxP3-transgenic mice based on impaired osteoclast differentiation
AU - Zaiss, Mario M
AU - Sarter, Kerstin
AU - Hess, Andreas
AU - Engelke, Klaus
AU - Böhm, Christina
AU - Nimmerjahn, Falk
AU - Voll, Reinhard
AU - Schett, Georg
AU - David, Jean-Pierre
PY - 2010/8/1
Y1 - 2010/8/1
N2 - OBJECTIVE: Immune activation triggers bone loss. Activated T cells are the cellular link between immune activation and bone destruction. The aim of this study was to determine whether immune regulatory mechanisms, such as naturally occurring Treg cells, also extend their protective effects to bone homeostasis in vivo.METHODS: Bone parameters in FoxP3-transgenic (Tg) mice were compared with those in their wild-type (WT) littermate controls. Ovariectomy was performed in FoxP3-Tg mice as a model of postmenopausal osteoporosis, and the bone parameters were analyzed. The bones of RAG-1(-/-) mice were analyzed following the adoptive transfer of isolated CD4+CD25+ T cells. CD4+CD25+ T cells and CD4+ T cells isolated from FoxP3-Tg mice and WT mice were cocultured with monocytes to determine their ability to suppress osteoclastogenesis in vitro.RESULTS: FoxP3-Tg mice developed higher bone mass and were protected from ovariectomy-induced bone loss. The increase in bone mass was found to be the result of impaired osteoclast differentiation and bone resorption in vivo. Bone formation was not affected. Adoptive transfer of CD4+CD25+ T cells into T cell-deficient RAG-1(-/-) mice also increased the bone mass, indicating that Treg cells directly affect bone homeostasis without the need to engage other T cell lineages.CONCLUSION: These data demonstrate that Treg cells can control bone resorption in vivo and can preserve bone mass during physiologic and pathologic bone remodeling.
AB - OBJECTIVE: Immune activation triggers bone loss. Activated T cells are the cellular link between immune activation and bone destruction. The aim of this study was to determine whether immune regulatory mechanisms, such as naturally occurring Treg cells, also extend their protective effects to bone homeostasis in vivo.METHODS: Bone parameters in FoxP3-transgenic (Tg) mice were compared with those in their wild-type (WT) littermate controls. Ovariectomy was performed in FoxP3-Tg mice as a model of postmenopausal osteoporosis, and the bone parameters were analyzed. The bones of RAG-1(-/-) mice were analyzed following the adoptive transfer of isolated CD4+CD25+ T cells. CD4+CD25+ T cells and CD4+ T cells isolated from FoxP3-Tg mice and WT mice were cocultured with monocytes to determine their ability to suppress osteoclastogenesis in vitro.RESULTS: FoxP3-Tg mice developed higher bone mass and were protected from ovariectomy-induced bone loss. The increase in bone mass was found to be the result of impaired osteoclast differentiation and bone resorption in vivo. Bone formation was not affected. Adoptive transfer of CD4+CD25+ T cells into T cell-deficient RAG-1(-/-) mice also increased the bone mass, indicating that Treg cells directly affect bone homeostasis without the need to engage other T cell lineages.CONCLUSION: These data demonstrate that Treg cells can control bone resorption in vivo and can preserve bone mass during physiologic and pathologic bone remodeling.
KW - Animals
KW - Bone Density
KW - Bone Resorption
KW - Bone and Bones
KW - CD4-Positive T-Lymphocytes
KW - Cell Differentiation
KW - Cells, Cultured
KW - Flow Cytometry
KW - Forkhead Transcription Factors
KW - Immunohistochemistry
KW - Mice
KW - Mice, Knockout
KW - Osteoclasts
KW - Ovariectomy
KW - Reverse Transcriptase Polymerase Chain Reaction
KW - T-Lymphocyte Subsets
U2 - 10.1002/art.27535
DO - 10.1002/art.27535
M3 - SCORING: Journal article
C2 - 20506516
VL - 62
SP - 2328
EP - 2338
JO - ARTHRITIS RHEUMATOL
JF - ARTHRITIS RHEUMATOL
SN - 2326-5191
IS - 8
ER -