title: Mesenchymal Stem Cells Repress Osteoblast Differentiation Under Osteogenic-Inducing Conditions.
abstract: This study was designed to investigate the influence of mesenchymal stem cells (MSCs) on osteoblast (OB) differentiation. Rat bone marrow MSCs were cultured either in growth medium that maintained a MSC phenotype or in osteogenic medium that induced differentiation into OBs. Then, cells were grown in two different culture conditions: indirect co-culture of MSCs and OBs and OBs cultured in MSC-conditioned medium. As a control culture condition, OBs were grown in osteogenic medium without the influence of MSCs. We evaluated cell proliferation, the gene expression of key bone markers, alkaline phosphatase (ALP) activity, bone sialoprotein (BSP) expression, and extracellular matrix mineralization. The results showed that, regardless of whether OBs were indirectly co-cultured with MSCs or cultured in MSC-conditioned medium, MSCs repressed OB differentiation, as evidenced by the downregulation of all evaluated bone marker genes, decreased ALP activity, inhibition of BSP protein expression, and reduced extracellular matrix mineralization. Taken together, these results indicate that despite the key role of both MSCs and OBs in the osteogenic process, the repressive effect of MSCs on OB differentiation in an osteogenic environment may represent a barrier to the strategy of using them together in cell-based therapies to induce bone repair.
authors.affiliation: Cell Culture Laboratory, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Thiago S
authors.initials: TS
authors.lastname: Santos
authors.affiliation: Cell Culture Laboratory, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Rodrigo P F
authors.initials: RP
authors.lastname: Abuna
authors.affiliation: Cell Culture Laboratory, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Larissa M S
authors.initials: LM
authors.lastname: Castro Raucci
authors.affiliation: Cell Culture Laboratory, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Lucas N
authors.initials: LN
authors.lastname: Teixeira
authors.affiliation: Cell Culture Laboratory, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Paulo T
authors.initials: PT
authors.lastname: de Oliveira
authors.affiliation: Cell Culture Laboratory, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Marcio M
authors.initials: MM
authors.lastname: Beloti
authors.affiliation: Cell Culture Laboratory, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Adalberto L
authors.initials: AL
authors.lastname: Rosa
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D005109:Extracellular Matrix / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology*; D010012:Osteogenesis / Q000235:genetics*; D051381:Rats
chemical_list: D017077:Culture Media, Conditioned
keywords: BONE MARROW; CELL CULTURE; DIFFERENTIATION; MESENCHYMAL STEM CELL; OSTEOBLAST