Loss of menin in osteoblast lineage affects osteocyte–osteoclast crosstalk causing osteoporosis
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 b...
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Veröffentlicht in: | Cell death and differentiation 2017-04, Vol.24 (4), p.672-682 |
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Sprache: | eng |
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Zusammenfassung: | 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. |
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ISSN: | 1350-9047 1476-5403 |
DOI: | 10.1038/cdd.2016.165 |