ISSN: 1449-1907International Journal of Medical Sciences
Global reach, higher impact
Int J Med Sci 2022; 19(8):1307-1319. doi:10.7150/ijms.70411 This issue Cite
Research Paper
LIM Mineralization Protein-1 Enhances the Committed Differentiation of Dental Pulp Stem Cells through the ERK1/2 and p38 MAPK Pathways and BMP Signaling
1. Department of Stomatology, Jinling Hospital, Medical School of Nanjing University, School of Stomatology of Southern Medical University, Clinical Medical School of Nanjing Medical University, Nanjing 210002, China.
2. Stomatology Center, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Guangdong province, Shenzhen 518036, China.
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.
Keywords: Dental pulp stem cells, Differentiation, LIM mineralization protein-1, Mitogen-activated protein kinase pathway, Tissue regeneration
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