Hdl Handle:
http://hdl.handle.net/10675.2/690
Title:
Profiling Insulin Like Factor 3 (INSL3) Signaling in Human Osteoblasts
Authors:
Ferlin, Alberto ( 0000-0002-0391-6570 ) ; Perilli, Lisa; Gianesello, Lisa; Taglialavoro, Giuseppe; Foresta, Carlo
Abstract:
Background: Young men with mutations in the gene for the INSL3 receptor (Relaxin family peptide 2, RXFP2) are at risk of reduced bone mass and osteoporosis. Consistent with the human phenotype, bone analyses of Rxfp2â /â mice showed decreased bone volume, alterations of the trabecular bone, reduced mineralizing surface, bone formation, and osteoclast surface. The aim of this study was to elucidate the INSL3/RXFP2 signaling pathways and targets in human osteoblasts.; Methodology/Principal Findings: Alkaline phosphatase (ALP) production, protein phosphorylation, intracellular calcium, gene expression, and mineralization studies have been performed. INSL3 induced a significant increase in ALP production, and Western blot and ELISA analyses of multiple intracellular signaling pathway molecules and their phosphorylation status revealed that the MAPK was the major pathway influenced by INSL3, whereas it does not modify intracellular calcium concentration. Quantitative Real Time PCR and Western blotting showed that INSL3 regulates the expression of different osteoblast markers. Alizarin red-S staining confirmed that INSL3-stimulated osteoblasts are fully differentiated and able to mineralize the extracellular matrix.; Conclusions/Significance: Together with previous findings, this study demonstrates that the INSL3/RXFP2 system is involved in bone metabolism by acting on the MAPK cascade and stimulating transcription of important genes of osteoblast maturation/differentiation and osteoclastogenesis.
Editors:
Mei, Lin
Citation:
PLoS One. 2011 Dec 28; 6(12):e29733
Issue Date:
28-Dec-2011
URI:
http://hdl.handle.net/10675.2/690
DOI:
10.1371/journal.pone.0029733
PubMed ID:
22216350
PubMed Central ID:
PMC3247287
Type:
Article
ISSN:
1932-6203
Appears in Collections:
Department of Neurology: Faculty Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorFerlin, Albertoen_US
dc.contributor.authorPerilli, Lisaen_US
dc.contributor.authorGianesello, Lisaen_US
dc.contributor.authorTaglialavoro, Giuseppeen_US
dc.contributor.authorForesta, Carloen_US
dc.contributor.editorMei, Lin-
dc.date.accessioned2012-10-26T16:29:34Z-
dc.date.available2012-10-26T16:29:34Z-
dc.date.issued2011-12-28en_US
dc.identifier.citationPLoS One. 2011 Dec 28; 6(12):e29733en_US
dc.identifier.issn1932-6203en_US
dc.identifier.pmid22216350en_US
dc.identifier.doi10.1371/journal.pone.0029733en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/690-
dc.description.abstractBackground: Young men with mutations in the gene for the INSL3 receptor (Relaxin family peptide 2, RXFP2) are at risk of reduced bone mass and osteoporosis. Consistent with the human phenotype, bone analyses of Rxfp2â /â mice showed decreased bone volume, alterations of the trabecular bone, reduced mineralizing surface, bone formation, and osteoclast surface. The aim of this study was to elucidate the INSL3/RXFP2 signaling pathways and targets in human osteoblasts.en_US
dc.description.abstractMethodology/Principal Findings: Alkaline phosphatase (ALP) production, protein phosphorylation, intracellular calcium, gene expression, and mineralization studies have been performed. INSL3 induced a significant increase in ALP production, and Western blot and ELISA analyses of multiple intracellular signaling pathway molecules and their phosphorylation status revealed that the MAPK was the major pathway influenced by INSL3, whereas it does not modify intracellular calcium concentration. Quantitative Real Time PCR and Western blotting showed that INSL3 regulates the expression of different osteoblast markers. Alizarin red-S staining confirmed that INSL3-stimulated osteoblasts are fully differentiated and able to mineralize the extracellular matrix.en_US
dc.description.abstractConclusions/Significance: Together with previous findings, this study demonstrates that the INSL3/RXFP2 system is involved in bone metabolism by acting on the MAPK cascade and stimulating transcription of important genes of osteoblast maturation/differentiation and osteoclastogenesis.en_US
dc.rightsFerlin et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.subjectResearch Articleen_US
dc.subjectBiologyen_US
dc.subjectMolecular Cell Biologyen_US
dc.subjectSignal Transductionen_US
dc.subjectMembrane Receptor Signalingen_US
dc.subjectHormone Receptor Signalingen_US
dc.subjectGene Expressionen_US
dc.subjectMedicineen_US
dc.subjectEndocrinologyen_US
dc.subject.meshAlkaline Phosphataseen_US
dc.subject.meshAnimalsen_US
dc.subject.meshBlotting, Westernen_US
dc.subject.meshCalciumen_US
dc.subject.meshEnzyme-Linked Immunosorbent Assayen_US
dc.subject.meshGene Expressionen_US
dc.subject.meshHumansen_US
dc.subject.meshInsulinen_US
dc.subject.meshMiceen_US
dc.subject.meshOsteoblastsen_US
dc.subject.meshPhosphorylationen_US
dc.subject.meshProteinsen_US
dc.subject.meshSignal Transductionen_US
dc.titleProfiling Insulin Like Factor 3 (INSL3) Signaling in Human Osteoblastsen_US
dc.typeArticleen_US
dc.identifier.pmcidPMC3247287en_US
dc.contributor.corporatenameDepartment of Neurology-
dc.contributor.corporatenameCollege of Graduate Studies-

Related articles on PubMed

All Items in Scholarly Commons are protected by copyright, with all rights reserved, unless otherwise indicated.