PMID- 28106886 OWN - NLM STAT- MEDLINE DCOM- 20180129 LR - 20220202 IS - 1476-5403 (Electronic) IS - 1350-9047 (Print) IS - 1350-9047 (Linking) VI - 24 IP - 4 DP - 2017 Apr TI - Loss of menin in osteoblast lineage affects osteocyte-osteoclast crosstalk causing osteoporosis. PG - 672-682 LID - 10.1038/cdd.2016.165 [doi] AB - 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. FAU - Liu, Peng AU - Liu P AD - Institute of Comparative Molecular Endocrinology, University of Ulm, Ulm D-89081, Germany. AD - Tissue-specific Hormone Action, Leibniz Institute on Aging-Fritz Lipmann Institute (FLI), Jena D-07745, Germany. FAU - Lee, Sooyeon AU - Lee S AD - Institute of Comparative Molecular Endocrinology, University of Ulm, Ulm D-89081, Germany. AD - Tissue-specific Hormone Action, Leibniz Institute on Aging-Fritz Lipmann Institute (FLI), Jena D-07745, Germany. FAU - Knoll, Jeanette AU - Knoll J AD - Tissue-specific Hormone Action, Leibniz Institute on Aging-Fritz Lipmann Institute (FLI), Jena D-07745, Germany. FAU - Rauch, Alexander AU - Rauch A AD - Tissue-specific Hormone Action, Leibniz Institute on Aging-Fritz Lipmann Institute (FLI), Jena D-07745, Germany. FAU - Ostermay, Susanne AU - Ostermay S AD - Tissue-specific Hormone Action, Leibniz Institute on Aging-Fritz Lipmann Institute (FLI), Jena D-07745, Germany. FAU - Luther, Julia AU - Luther J AD - Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg D-20246, Germany. FAU - Malkusch, Nicole AU - Malkusch N AD - Institute of Comparative Molecular Endocrinology, University of Ulm, Ulm D-89081, Germany. FAU - Lerner, Ulf H AU - Lerner UH AD - Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition at Institute for Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg SE-41345, Sweden. FAU - Zaiss, Mario M AU - Zaiss MM AD - Department of Internal Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nurnberg (FAU) and Universitatsklinikum Erlangen, Erlangen D-91054, Germany. FAU - Neven, Mona AU - Neven M AD - Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg D-20246, Germany. FAU - Wittig, Rainer AU - Wittig R AD - Institute for Laser Technologies in Medicine and Metrology at Ulm University, Ulm D-89081, Germany. FAU - Rauner, Martina AU - Rauner M AD - Division of Endocrinology and Bone Diseases, Department of Medicine III, TU Dresden, Dresden D-01307, Germany. FAU - David, Jean-Pierre AU - David JP AD - Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg D-20246, Germany. AD - Department of Internal Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nurnberg (FAU) and Universitatsklinikum Erlangen, Erlangen D-91054, Germany. FAU - Bertolino, Philippe AU - Bertolino P AUID- ORCID: 0000-0001-8064-8269 AD - Centre de Recherche en Cancerologie de Lyon, Inserm U1052, CNRS UMR5286, Universite Lyon 1, Lyon F-69000, France. FAU - Zhang, Chang X AU - Zhang CX AD - Centre de Recherche en Cancerologie de Lyon, Inserm U1052, CNRS UMR5286, Universite Lyon 1, Lyon F-69000, France. FAU - Tuckermann, Jan P AU - Tuckermann JP AD - Institute of Comparative Molecular Endocrinology, University of Ulm, Ulm D-89081, Germany. AD - Tissue-specific Hormone Action, Leibniz Institute on Aging-Fritz Lipmann Institute (FLI), Jena D-07745, Germany. LA - eng PT - Journal Article DEP - 20170120 PL - England TA - Cell Death Differ JT - Cell death and differentiation JID - 9437445 RN - 0 (Antibodies, Neutralizing) RN - 0 (Chemokine CXCL10) RN - 0 (Men1 protein, mouse) RN - 0 (Proto-Oncogene Proteins) RN - 0 (Sp7 Transcription Factor) RN - 0 (Sp7 protein, mouse) RN - EC 3.1.3.1 (ALPL protein, mouse) RN - EC 3.1.3.1 (Alkaline Phosphatase) SB - IM MH - Alkaline Phosphatase/genetics/metabolism MH - Animals MH - Antibodies, Neutralizing/administration & dosage/immunology MH - Bone Marrow Cells/cytology MH - Cell Communication/*physiology MH - Cell Differentiation MH - Cell Lineage MH - Cells, Cultured MH - Chemokine CXCL10/genetics/immunology/metabolism MH - Female MH - Femur/diagnostic imaging MH - Mice MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - Osteoclasts/cytology/metabolism MH - Osteocytes/cytology/metabolism MH - Osteogenesis MH - Osteoporosis/etiology/metabolism/pathology MH - Proto-Oncogene Proteins/deficiency/genetics/*metabolism MH - Sp7 Transcription Factor/genetics/metabolism PMC - PMC5384024 COIS- The authors declare no conflict of interest. EDAT- 2017/01/21 06:00 MHDA- 2018/01/30 06:00 PMCR- 2017/04/01 CRDT- 2017/01/21 06:00 PHST- 2016/06/30 00:00 [received] PHST- 2016/12/08 00:00 [revised] PHST- 2016/12/20 00:00 [accepted] PHST- 2017/01/21 06:00 [pubmed] PHST- 2018/01/30 06:00 [medline] PHST- 2017/01/21 06:00 [entrez] PHST- 2017/04/01 00:00 [pmc-release] AID - cdd2016165 [pii] AID - 10.1038/cdd.2016.165 [doi] PST - ppublish SO - Cell Death Differ. 2017 Apr;24(4):672-682. doi: 10.1038/cdd.2016.165. Epub 2017 Jan 20.