title: Strontium ranelate increases osteoblast activity.
abstract: Strontium ranelate (SR) is the first generation of a new class of medication for osteoporosis, which is capable of inducing bone formation and, to a certain extent, inhibiting bone resorption. The aim of this study was to evaluate the in vitro effects of SR on osteoblastic cell cultures. MC3TE-E1 cells were seeded in 24-well plates at a density of 2×10(4) cells/well and exposed to SR at 0.05, 0.1, and 0.5mM. The following parameters were assayed: 1) Cell proliferation by hemocytometer counting after 24, 48 and 72h, 2) Cell viability by MTT assay after 24, 48 and 72h, 3) Type I Collagen and Osteopontin (OPN) quantification by Western Blotting, ELISA, and Real Time PCR after 48h, 3) Immunolocalization of fibronectin (FN) by epifluorescence, and 4) matrix mineralization by Alizarin Red staining after 14days. After 24, 48 and 72h, the cell proliferation and viability were not affected by SR at 0.05 and 0.1mM (p>0.05). However, cell cultures exposed to SR at 0.5mM exhibited a decrease in both cell proliferation and cell viability in all time points assayed (p<0.05). High levels of protein and mRNA for Type I Collagen and OPN were detected in cultures exposed to SR, particularly at 0.5mM (p<0.05). SR allowed the expression of FN in osteoblastic cell cultures as observed by epifluorescence analysis. The mineralized bone-like nodule formation was affected in a concentration-dependent manner by SR, with large bone-like nodules being detected in osteoblastic cell cultures exposed to SR at 0.5mM. In conclusion, these results suggest that SR can accelerate acquisition of the osteoblastic phenotype, which explains, at least in part, the rebalancing of bone turnover in favor of bone formation.
authors.affiliation: Laboratory of Immunology and Molecular Biology, São Leopoldo Mandic Institute and Research Center, Campinas, SP, Brazil.
authors.forename: Monica Marletti
authors.initials: MM
authors.lastname: Almeida
authors.affiliation: Laboratory of Immunology and Molecular Biology, São Leopoldo Mandic Institute and Research Center, Campinas, SP, Brazil.
authors.forename: Edson Parra
authors.initials: EP
authors.lastname: Nani
authors.affiliation: Department of Oral Pathology, São Leopoldo Mandic Institute and Research Center, Campinas, SP, Brazil.
authors.forename: Lucas Novaes
authors.initials: LN
authors.lastname: Teixeira
authors.affiliation: Laboratory of Immunology and Molecular Biology, São Leopoldo Mandic Institute and Research Center, Campinas, SP, Brazil.
authors.forename: Daiane Cristina
authors.initials: DC
authors.lastname: Peruzzo
authors.affiliation: Laboratory of Immunology and Molecular Biology, São Leopoldo Mandic Institute and Research Center, Campinas, SP, Brazil.
authors.forename: Júlio César
authors.initials: JC
authors.lastname: Joly
authors.affiliation: Laboratory of Immunology and Molecular Biology, São Leopoldo Mandic Institute and Research Center, Campinas, SP, Brazil.
authors.forename: Marcelo Henrique
authors.initials: MH
authors.lastname: Napimoga
authors.affiliation: Department of Oral Pathology, São Leopoldo Mandic Institute and Research Center, Campinas, SP, Brazil. Electronic address: dr.efmartinez@gmail.com.
authors.forename: Elizabeth Ferreira
authors.initials: EF
authors.lastname: Martinez
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001862:Bone Resorption / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002113:Calcification, Physiologic / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics*; D049109:Cell Proliferation / Q000187:drug effects*; D024042:Collagen Type I / Q000096:biosynthesis; D000090602:Collagen Type I, alpha 1 Chain; D005353:Fibronectins / Q000096:biosynthesis; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D053495:Osteopontin / Q000096:biosynthesis; D010024:Osteoporosis / Q000188:drug therapy* / Q000473:pathology; D013876:Thiophenes / Q000008:administration & dosage*
chemical_list: D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D005353:Fibronectins; D013876:Thiophenes; C081587:strontium ranelate; D053495:Osteopontin
keywords: Bone; Osteoblasts; Strontium ranelate