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Loss of menin in os...
Loss of menin in osteoblast lineage affects osteocyte-osteoclast crosstalk causing osteoporosis
- Article/chapterEnglish2017
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2017-01-20
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Springer Science and Business Media LLC,2017
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LIBRIS-ID:oai:gup.ub.gu.se/252712
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https://gup.ub.gu.se/publication/252712URI
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https://doi.org/10.1038/cdd.2016.165DOI
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
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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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Lee, S.
(author)
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Knoll, J.
(author)
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Rauch, A.
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Ostermay, S.
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Luther, J.
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Malkusch, N.
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Lerner, Ulf HGothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition(Swepub:gu)xlerul
(author)
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Zaiss, M. M.
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Neven, M.
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Wittig, R.
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Rauner, M.
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David, J. P.
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Bertolino, P.
(author)
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Zhang, C. X.
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Tuckermann, J. P.
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Göteborgs universitetCentre for Bone and Arthritis Research
(creator_code:org_t)
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In:Cell Death and Differentiation: Springer Science and Business Media LLC24:4, s. 672-6821350-90471476-5403
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Liu, P.
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Lee, S.
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Knoll, J.
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Rauch, A.
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Ostermay, S.
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Luther, J.
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Malkusch, N.
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Lerner, Ulf H
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Zaiss, M. M.
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Neven, M.
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Wittig, R.
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Rauner, M.
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David, J. P.
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Bertolino, P.
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Zhang, C. X.
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Tuckermann, J. P ...
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NATURAL SCIENCES
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NATURAL SCIENCES
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Cell Death and D ...
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University of Gothenburg