Binder, Nikolaus B. and Niederreiter, Birgit and Hoffmann, Oskar and Stange, Richard and Pap, Thomas and Stulnig, Thomas M. and Mack, Matthias and Erben, Reinhold G. and Smolen, Josef S. and Redlich, Kurt (2009) Estrogen-dependent and C-C chemokine receptor-2-dependent pathways determine osteoclast behavior in osteoporosis. NATURE MEDICINE, 15 (4). pp. 417-424. ISSN 1078-8956, 1546-170X
Full text not available from this repository. (Request a copy)Abstract
Understanding the mechanisms of osteoclastogenesis is crucial for developing new drugs to treat diseases associated with bone loss, such as osteoporosis. Here we report that the C-C chemokine receptor-2 (CCR2) is crucially involved in balancing bone mass. CCR2-knockout mice have high bone mass owing to a decrease in number, size and function of osteoclasts. In normal mice, activation of CCR2 in osteoclast progenitor cells results in both nuclear factor-kappa B (NF-kappa B) and extracellular signal-related kinase 1 and 2 (ERK1/2) signaling but not that of p38 mitogen-activated protein kinase or c-Jun N-terminal kinase. The induction of NF-kappa B and ERK1/2 signaling in turn leads to increased surface expression of receptor activator of NF-kappa B (RANK, encoded by Tnfrsf11a), making the progenitor cells more susceptible to RANK ligand-induced osteoclastogenesis. In ovariectomized mice, a model of postmenopausal osteoporosis, CCR2 is upregulated on wild-type preosteoclasts, thus increasing the surface expression of RANK on these cells and their osteoclastogenic potential, whereas CCR2-knockout mice are resistant to ovariectomy-induced bone loss. These data reveal a previously undescribed pathway by which RANK, osteoclasts and bone homeostasis are regulated in health and disease.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | BONE-MINERAL DENSITY; KAPPA-B LIGAND; RECEPTOR ACTIVATOR; MULTIPLE-MYELOMA; NECROSIS-FACTOR; EXPRESSION; CELLS; RESORPTION; CYTOKINE; HORMONE; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 18 Sep 2020 14:59 |
| Last Modified: | 18 Sep 2020 14:59 |
| URI: | https://pred.uni-regensburg.de/id/eprint/29202 |
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