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

Autor: Nicole Malkusch, Jeanette Knoll, Sooyeon Lee, Ulf H. Lerner, Jan Tuckermann, Mario M. Zaiss, Mona Neven, Susanne Ostermay, Alexander Rauch, Julia Luther, Philippe Bertolino, Martina Rauner, Chang X. Zhang, Peng Liu, Jean-Pierre David, Rainer Wittig
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
Zelle
endocrine system diseases
receptor
Osteoporosis
Osteoclasts
Bone resorption
Expression
Cell Communication
Mice
DDC 570 / Life sciences
Osteogenesis
Cell differentiation
Femur
Cells
Cultured
Gen
Chemistry
Osteoblast
Cell Differentiation
differentiation
Maus
endocrine neoplasia type-1
Cell biology
Crosstalk (biology)
medicine.anatomical_structure
Sp7 Transcription Factor
Osteocyte
Female
Chemokines
musculoskeletal diseases
medicine.medical_specialty
congenital
hereditary
and neonatal diseases and abnormalities
endocrine system
Cells
Zelldifferenzierung
Bone Marrow Cells
Mice
Transgenic
Osteocytes
03 medical and health sciences
Ausdruck
Osteoclast
Internal medicine
ddc:570
Proto-Oncogene Proteins
medicine
CXCL10
Animals
MEN1
Cell Lineage
Glucocorticosteroide
gene
Molecular Biology
Glucocorticoids
mouse
Original Paper
Cell Biology
cell
medicine.disease
Alkaline Phosphatase
Antibodies
Neutralizing
Chemokine CXCL10
Mice
Inbred C57BL
030104 developmental biology
Endocrinology
Genes
Zdroj: Cell Death and Differentiation
Cell death and differentiation, 24:672-682
ISSN: 1476-5403
1350-9047
Popis: 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.
publishedVersion
Databáze: OpenAIRE
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