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Influence of patented jaboticaba peel extract (PJE) on the processes of osteoblastic and adipocytic differentiation of mesenchymal stem cells derived from bone marrow and adipose tissue

Grant number: 19/14506-0
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): September 01, 2019
Effective date (End): August 31, 2020
Field of knowledge:Health Sciences - Dentistry - Oral and Maxillofacial Surgery
Principal Investigator:Márcio Mateus Beloti
Grantee:Sofia Garibaldi Otavio
Home Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Several natural products have been investigated for therapeutic purposes, such as preventing metabolic damage. Fruits can be an important source of various bioactive compounds mainly concentrated in their peel. Among them, the jaboticaba peel has been indicated as a promising product in the treatment of obesity. Since the increase in bone marrow adipogenesis is correlated with a decrease in bone mineral density, which are directly influenced by the osteoblastic and adipocytic differentiation of mesenchymal stem cells (MSCs), the patented jaboticaba peel extract (PJE) could act in these cells as a growth factor preventing the negative effect that bone marrow adiposity generates on bone tissue, including in the repair of fractures. In this context, the aim of the present project is to evaluate the effect of PJE on the osteoblastic and adipocytic differentiation of bone marrow-derived mesenchymal stem cells (BM-MSCs) and adipose tissue-derived MSCs (AT-MSCs). Cells will be cultured in growth medium in the presence of different concentrations of PJE (0.25 ¼g/mL, 2.5 ¼g/mL, 25 ¼g/mL and 250 ¼g/mL) and vehicle (Control-distilled water), and the highest concentration of PJE that does not affect cell proliferation will be selected. Then, BM-MSCs and AT-MSCs will be cultured in osteogenic medium or adipogenic medium, in the presence or absence of PJE at the predetermined concentration and it will be evaluated (1) the osteoblastic parameters: in situ alkaline phosphatase (ALP) activity, the formation of mineralized extracellular matrix and gene expression of the transcription factor related to runt 2 (Runx2), Alp, bone sialoprotein (Bsp) and osteocalcin (Oc) by real-time PCR; and (2) the adipocyte parameters: formation of lipid accumulation and gene expression of peroxisome proliferator-activated receptors gamma (Ppar³), adipocytic protein 2 (aP2) and resistin (Retn). The data will be submitted to the normal curve adherence test to determine the appropriate statistical test. Considering the interrelationship between bone and fat, and that such interactions may impair bone metabolism, the results of this study may contribute to the development of new strategies involving MSCs and PJE that favor events related to relevant clinical situations such as the repair of bone fractures.