Loss of menin in osteoblast lineage affects osteocyte-osteoclast crosstalk causing osteoporosis

Liu P, Lee S, Knoll J, Rauch A, Ostermay S, Luther J, Malkusch N, Lerner UH, Zaiss M, Neven M, Wittig R, Rauner M, David JP, Bertolino P, Zhang CX, Tuckermann JP (2017)

Publication Type: Journal article

Publication year: 2017

Journal

Cell Death and Differentiation Nature Publishing Group: Open Access Hybrid Model Option B

DOI: 10.1038/cdd.2016.165

Abstract

During osteoporosis bone formation by osteoblasts is reduced and/or bone resorption by osteoclasts is enhanced. Currently, only a few factors have been identified in the regulation of bone integrity by osteoblast-derived osteocytes. In this study, we show that specific disruption of menin, encoded by multiple endocrine neoplasia type 1 (Men1), in osteoblasts and osteocytes caused osteoporosis despite the preservation of osteoblast differentiation and the bone formation rate. Instead, an increase in osteoclast numbers and bone resorption was detected that persisted even when the deletion of Men1 was restricted to osteocytes. We demonstrate that isolated Men1-deficient osteocytes expressed numerous soluble mediators, such as C-X-C motif chemokine 10 (CXCL10), and that CXCL10-mediated osteoclastogenesis was reduced by CXCL10-neutralizing antibodies. Collectively, our data reveal a novel role for Men1 in osteocyte-osteoclast crosstalk by controlling osteoclastogenesis through the action of soluble factors. A role for Men1 in maintaining bone integrity and thereby preventing osteoporosis is proposed.Cell Death and Differentiation advance online publication, 20 January 2017; doi:10.1038/cdd.2016.165.

Authors with CRIS profile

Mario Zaiss Department of Medicine 3 – Rheumatology and Immunology

Involved external institutions

Universität Ulm DE Germany (DE) Université Claude Bernard Lyon 1 (UCB) FR France (FR) Universitätsklinikum Hamburg-Eppendorf (UKE) DE Germany (DE) Technische Universität Dresden DE Germany (DE) University of Gothenburg / Göteborgs universitet SE Sweden (SE) Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut (FLI) DE Germany (DE)

How to cite

APA:

Liu, P., Lee, S., Knoll, J., Rauch, A., Ostermay, S., Luther, J.,... Tuckermann, J.P. (2017). Loss of menin in osteoblast lineage affects osteocyte-osteoclast crosstalk causing osteoporosis. Cell Death and Differentiation. https://doi.org/10.1038/cdd.2016.165

MLA:

Liu, Peng, et al. "Loss of menin in osteoblast lineage affects osteocyte-osteoclast crosstalk causing osteoporosis." Cell Death and Differentiation (2017).

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