title: Silencing of RB1 and RB2/P130 during adipogenesis of bone marrow stromal cells results in dysregulated differentiation.
abstract: Bone marrow adipose tissue (BMAT) is different from fat found elsewhere in the body, and only recently have some of its functions been investigated. BMAT may regulate bone marrow stem cell niche and plays a role in energy storage and thermogenesis. BMAT may be involved also in obesity and osteoporosis onset. Given the paramount functions of BMAT, we decided to better clarify the human bone marrow adipogenesis by analyzing the role of the retinoblastoma gene family, which are key players in cell cycle regulation. Our data provide evidence that the inactivation of RB1 or RB2/P130 in uncommitted bone marrow stromal cells (BMSC) facilitates the first steps of adipogenesis. In cultures with silenced RB1 or RB2/P130, we observed an increase of clones with adipogenic potential and a higher percentage of cells accumulating lipid droplets. Nevertheless, the absence of RB1 or RB2/P130 impaired the terminal adipocyte differentiation and gave rise to dysregulated adipose cells, with alteration in lipid uptake and release. For the first time, we evidenced that RB2/P130 plays a role in bone marrow adipogenesis. Our data suggest that while the inactivation of retinoblastoma proteins may delay the onset of last cell division and allow more BMSC to be committed to adipocyte, it did not allow a permanent cell cycle exit, which is a prerequisite for adipocyte terminal maturation.
authors.affiliation: Department of Experimental Medicine; Biotechnology and Molecular Biology Section; Second University of Naples; Naples, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Capasso
authors.affiliation: Department of Experimental Medicine; Biotechnology and Molecular Biology Section; Second University of Naples; Naples, Italy; Institute of Protein Biochemistry; CNR; Naples, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Alessio
authors.affiliation: Department of Experimental Medicine; Biotechnology and Molecular Biology Section; Second University of Naples; Naples, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Di Bernardo
authors.affiliation: Department of Experimental Medicine; Biotechnology and Molecular Biology Section; Second University of Naples; Naples, Italy.
authors.forename: Marilena
authors.initials: M
authors.lastname: Cipollaro
authors.affiliation: Department of Clinical and Experimental Medicine; Second University of Naples; Naples, Italy.
authors.forename: Mariarosa Ab
authors.initials: MA
authors.lastname: Melone
authors.affiliation: Institute of Protein Biochemistry; CNR; Naples, Italy; Institute of Biomedicine and Bioresources; CNR; Naples, Italy.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Peluso
authors.affiliation: Sbarro Institute for Cancer Research and Molecular Medicine; Center For Biotechnology; Temple University; Philadelphia, PA USA; Department of Medicine, Surgery and Neurociences; University of Siena; Siena, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Giordano
authors.affiliation: Department of Experimental Medicine; Biotechnology and Molecular Biology Section; Second University of Naples; Naples, Italy; Institute of Protein Biochemistry; CNR; Naples, Italy; Sbarro Institute for Cancer Research and Molecular Medicine; Center For Biotechnology; Temple University; Philadelphia, PA USA; GENKÖK; Genome and Stem Cell Center; Erciyes University; Kayseri, Turkey.
authors.forename: Umberto
authors.initials: U
authors.lastname: Galderisi
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D050156:Adipogenesis; D001853:Bone Marrow / Q000378:metabolism; D002453:Cell Cycle; D002454:Cell Differentiation; D002478:Cells, Cultured; D020868:Gene Silencing; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism*; D050717:Retinoblastoma-Like Protein p130 / Q000235:genetics / Q000378:metabolism*
chemical_list: C493837:RBL2 protein, human; D016160:Retinoblastoma Protein; D050717:Retinoblastoma-Like Protein p130
keywords: adipocytes; bone marrow; differentiation; marrow stromal stem cells; retinoblastoma gene family