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Role of Extracellular Signal-Regulated Kinases (ERKs) on Osteoblast and Adipoblast Phenotype Expression of Mesenchymal Stem-Cells Cultured on Titanium with Nanotopography

Grant number: 15/04630-4
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): July 01, 2015
Effective date (End): June 30, 2016
Field of knowledge:Health Sciences - Dentistry - Oral and Maxillofacial Surgery
Principal researcher:Márcio Mateus Beloti
Grantee:Leonardo Pimentel Fiori
Home Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil


Titanium (Ti) with nanotopography enhances bone formation in close contact with implant surface, which is essential for osseointegration. Ti osseointegration may be affected by imbalances between osteogenic and adipogenic differentiation related to aging and diseases such as osteoporosis. The differentiation of bone marrow mesenchymal stem cells (BMMSCs) into either osteoblasts or adipoblasts is regulated by critical transcription factors runt-related transcription factor 2 (Runx2) and peroxime proliferator-activated receptor gamma (PPAR³), respectively. It has been shown that extracellular signal-regulated kinases (ERKs), specifically ERK 1/2, members of the mitogen-activated protein kinases (MAPKs) family, acts as a switch for the reciprocal regulation of osteogenesis and adipogenesis by modulating Runx2 and PPAR³ expression and/or activity. Considering this, it is possible to hypothesize that the positive effect of Ti surfaces with nanotopography on osteogenesis is, at least partially, due to a modulation of ERK/Runx2/PPAR³ interactions and a consequent balance between osteoblast and adipoblast phenotype expression of BMMSCs. To test this hypothesis, rat BMMSCs will be cultured in osteogenic and adipogenic medium on Ti surfaces with nanotopography and machined (untreated, control) for periods of up to 17 days, in the presence or absence of an inhibitor (PD98059) signaling pathway ERKs. The following parameters will be assessed: 1) gene expression of ERK1/2, Runx2 and PPAR³ in osteogenic and adipogenic cultures at day 10; 2) mineralized matrix formation by Alizarin red S staining at day 17 days in osteogenic cultures and 3) Oil red O Staining at day 17 in adipogenic cultures.