Effects of type 1 and 2 diabetes mellitus on the osteoblastic differentiation process of mesenchymal stem cells

Author(s)

Denise Weffort

• Document type: Master's Dissertation
• Press: Ribeirão Preto.
• Institution: Universidade de São Paulo (USP). Faculdade de Odontologia de Ribeirão Preto (PCARP/BC)
• Defense date: 2023-01-26

Examining board members

Adalberto Luiz Rosa; Emanuela Prado Ferraz; Gileade Pereira Freitas; Roberta Okamoto

• Advisor: Adalberto Luiz Rosa

Abstract

Diabetes mellitus (DM) is a group of diseases that can be divided into two main types: type 1 (DM1), which is characterized by the absence of insulin production and type 2 (DM2), which is a combination of resistance to and reduced production of insulin, both types lead to hyperglycemia. Inadequate control of hyperglycemia leads to complications in various organs such as the kidneys, eyes, vessels, and the relationship between DM and bone tissue. It is known that osteoblasts under high glucose concentrations present reduced proliferation, expression of genes involved in osteoblastic differentiation, and formation of mineralized nodules. However, there are no studies comparing the distinct negative effects on osteoblastic differentiation induced by DM1 and DM2 and investigating which cell signaling pathways could be involved in this process. Therefore, the objective of this study was to evaluate the effect of DM types 1 and 2 on osteoblastic differentiation of mesenchymal stem cells (MSCs) and the participation of BMP, WNT and integrin (ITG) signaling pathways, which are among the main pathways that operate in this process. For this, DM1 and DM2 were induced in Wistar rats and MSCs were harvested from femurs and cultured under osteogenic conditions, to induce osteoblastic differentiation, and hyperglycemic conditions. Cell proliferation, alkaline phosphatase (ALP) activity, mineralized extracellular matrix formation, gene expression of osteoblastic markers, factor transcription related to runt2 (Runx2), osterix, Alp, bone sialoprotein and osteocalcin and RUNX2 protein expression were evaluated. Gene expression of components of the BMP, WNT and ITG signaling pathways was also evaluated. The results indicated that DM decreases cell proliferation, ALP activity, the expression of osteoblastic genes, and the formation of mineralized nodules, with DM1 being more severe than DM2. The evaluated signaling pathways also showed a greater number of genes with negative modulation in DM1. However, when cultivating MSCs under normoglycemic conditions, DM1 cells developed partial recovery of osteoblastic potential, which did not occur in DM2 MSCs. (AU)

• FAPESP's process: 19/18711-7 - Effect of diabete mellitus on osteoblastic differentiation of mesenchymal stem cells
• Grantee: Denise Weffort
• Support Opportunities: Scholarships in Brazil - Master