PI3K/AKT signaling mediate collagen type 1-induced osteogenic differentiation of dental pulp stem cells via focal adhesion mechanism.

Abstract

Background: Dental pulp stem cells (DPSCs) are widely available sources of stem cells that have been extensively studied for its capacity to differentiate into osteoblasts and endothelial cells and to support bone repair and regeneration. Collagen type 1 (Col-1) is a well-known extracellular matrix component, which plays a vital role in regulating the signaling pathway for osteoinduction of bone progenitor cells. However, the exact mechanism of Col-1 activation during stem cell osteogenesis remains unclear.

Objectives: This study aims to identify the key signalling pathway and proteins interaction associated with Col-1-induced osteogenesis of DPSCs.

Methodology: The localization of OCN protein was assessed by immunocytochemistry analysis, followed by Western blot analysis on OCN, AKT, p- AKT, Smad2/3, p-Smad2/3, ERK1/2, and p-ERK1/2 pathways. Protein profiling was performed using gel-free digestion and LC-MS/MS, followed by protein-protein interaction analysis using STRING online tools to assist in determination of link between various pathways.

Results: The data indicated that the PI3K/AKT pathway is the key signaling pathway involved in Col-1-induced DPSC, showing a significant impact and potential crosstalk with TGF-b/Smad and MAPK/ERK mainly via focal adhesion protein complexes.

Conclusion: The evidence suggests that PI3K/AKT signaling pathway is more dominant than the TGF-β/Smad and MAPK/ERK pathways, acting via stimulation of the focal adhesion protein complex. Together, these findings may provide deeper insight into cellular biology of differentiated cells for potential manipulation in bone tissue repair and regeneration.