title: Loss of menin in osteoblast lineage affects osteocyte-osteoclast crosstalk causing osteoporosis.
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.
authors.affiliation: Institute of Comparative Molecular Endocrinology, University of Ulm, Ulm D-89081, Germany.|Tissue-specific Hormone Action, Leibniz Institute on Aging-Fritz Lipmann Institute (FLI), Jena D-07745, Germany.
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.affiliation: Institute of Comparative Molecular Endocrinology, University of Ulm, Ulm D-89081, Germany.|Tissue-specific Hormone Action, Leibniz Institute on Aging-Fritz Lipmann Institute (FLI), Jena D-07745, Germany.
authors.forename: Sooyeon
authors.initials: S
authors.lastname: Lee
authors.affiliation: Tissue-specific Hormone Action, Leibniz Institute on Aging-Fritz Lipmann Institute (FLI), Jena D-07745, Germany.
authors.forename: Jeanette
authors.initials: J
authors.lastname: Knoll
authors.affiliation: Tissue-specific Hormone Action, Leibniz Institute on Aging-Fritz Lipmann Institute (FLI), Jena D-07745, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Rauch
authors.affiliation: Tissue-specific Hormone Action, Leibniz Institute on Aging-Fritz Lipmann Institute (FLI), Jena D-07745, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Ostermay
authors.affiliation: Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg D-20246, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Luther
authors.affiliation: Institute of Comparative Molecular Endocrinology, University of Ulm, Ulm D-89081, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Malkusch
authors.affiliation: 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.
authors.forename: Ulf H
authors.initials: UH
authors.lastname: Lerner
authors.affiliation: Department of Internal Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen D-91054, Germany.
authors.forename: Mario M
authors.initials: MM
authors.lastname: Zaiss
authors.affiliation: Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg D-20246, Germany.
authors.forename: Mona
authors.initials: M
authors.lastname: Neven
authors.affiliation: Institute for Laser Technologies in Medicine and Metrology at Ulm University, Ulm D-89081, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Wittig
authors.affiliation: Division of Endocrinology and Bone Diseases, Department of Medicine III, TU Dresden, Dresden D-01307, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Rauner
authors.affiliation: Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg D-20246, Germany.|Department of Internal Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen D-91054, Germany.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: David
authors.affiliation: Centre de Recherche en Cancérologie de Lyon, Inserm U1052, CNRS UMR5286, Université Lyon 1, Lyon F-69000, France.
authors.forename: Philippe
authors.identifier: 0000-0001-8064-8269
authors.initials: P
authors.lastname: Bertolino
authors.affiliation: Centre de Recherche en Cancérologie de Lyon, Inserm U1052, CNRS UMR5286, Université Lyon 1, Lyon F-69000, France.
authors.forename: Chang X
authors.initials: CX
authors.lastname: Zhang
authors.affiliation: Institute of Comparative Molecular Endocrinology, University of Ulm, Ulm D-89081, Germany.|Tissue-specific Hormone Action, Leibniz Institute on Aging-Fritz Lipmann Institute (FLI), Jena D-07745, Germany.
authors.forename: Jan P
authors.initials: JP
authors.lastname: Tuckermann
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D057134:Antibodies, Neutralizing / Q000008:administration & dosage / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology; D002450:Cell Communication / Q000502:physiology*; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D054357:Chemokine CXCL10 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism; D010011:Osteocytes / Q000166:cytology / Q000378:metabolism; D010012:Osteogenesis; D010024:Osteoporosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000076182:Sp7 Transcription Factor / Q000235:genetics / Q000378:metabolism
chemical_list: D057134:Antibodies, Neutralizing; D054357:Chemokine CXCL10; C484898:Men1 protein, mouse; D011518:Proto-Oncogene Proteins; D000076182:Sp7 Transcription Factor; C479466:Sp7 protein, mouse; C510878:ALPL protein, mouse; D000469:Alkaline Phosphatase