LIM Mineralization Protein-1 Enhances the Committed Differentiation of Dental Pulp Stem Cells through the ERK1/2 and p38 MAPK Pathways and BMP Signaling

Abstract

Tissue regeneration is the preferred treatment for dentin and bone tissue defects. Dental pulp stem cells (DPSCs) have been extensively studied for their use in tissue regeneration, including the regeneration of dentin and bone tissue. LIM mineralization protein-1 (LMP-1) is an intracellular non-secretory protein that plays a positive regulatory role in the mineralization process. In this study, an LMP-1-induced DPSCs model was used to explore the effect of LMP-1 on the proliferation and odonto/osteogenic differentiation of DPSCs, as well as the underlying mechanisms. As indicated by the cell counting kit-8 assay, the results showed that LMP-1 did not affect the proliferation of DPSCs. Overexpression of LMP-1 significantly promoted the committed differentiation of DPSCs and vice versa, as shown by alkaline phosphatase activity assay, alizarin red staining, western blot assay, quantitative real-time polymerase chain reaction assay, and in vivo mineralized tissue formation assay. Furthermore, inhibiting the activation of the extracellular signal-regulated kinase 1/2 (ERK1/2), p38 mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK) pathways using specific pathway inhibitors showed that the ERK1/2 and p38 MAPK pathways attenuated the differentiation of DPSCs. Besides, the expression of BMP signaling pathway components were also determined, which suggested that LMP-1 could activate BMP-2/Smad1/5 signaling pathway. Our results not only indicated the underlying mechanism of LMP-1 treated DPSCs but also provided valuable insight into therapeutic strategies in regenerative medicine.

PDZ and LIM Domain-Encoding Genes: Their Role in Cancer Development

“…Due to its osteoinductive properties, PDLIM7 recruits many bone-forming factors [72,73]. The overexpression of PDLIM7 upregulates TGF-β, BMP2, BMP-4, BMP-6, BMP-7, and BMP receptors [74][75][76][77][78][79]. For example, PDLIM7 is able to activate the BMP-2/Smad1/5 signaling pathway and induces the process of pulp/osteogenic differentiation of dental pulp stem cells.…”

Characterization of a Stemness-Optimized Purification Method for Human Dental-Pulp Stem Cells: An Approach to Standardization

“…Ideally, cells that are administered for dental pulp regeneration purposes would support dentin synthesis, enable an efficient dentin-pulp/soft tissue interaction, withstand hypoxia, facilitate anti-inflammatory and regenerative molecular signaling pathways, while building a hard tissue barrier towards potentially inserted repair materials [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ]. In the light of their proliferative capacity, their developmental potential, as well as their self-regenerative properties, SCs are optimal candidates for such applications.…”