Lysophosphatidic acid induces proliferation and osteogenic differentiation of human dental pulp stem cell through lysophosphatidic acid receptor 3/extracellular signal-regulated kinase signaling axis

Soon Chul Heo; Bo Ram Keum; Eun Jin Seo; Jinhwan Yoon; Sanghwa Jeong; Gabor J Tigyi; Derek Norman; Il Ho Jang; Hyung Joon Kim

doi:10.1016/j.jds.2023.01.029

Lysophosphatidic acid induces proliferation and osteogenic differentiation of human dental pulp stem cell through lysophosphatidic acid receptor 3/extracellular signal-regulated kinase signaling axis

J Dent Sci. 2023 Jul;18(3):1219-1226. doi: 10.1016/j.jds.2023.01.029. Epub 2023 Feb 9.

Authors

Soon Chul Heo¹, Bo Ram Keum¹, Eun Jin Seo², Jinhwan Yoon³, Sanghwa Jeong⁴, Gabor J Tigyi⁵, Derek Norman⁵, Il Ho Jang², Hyung Joon Kim¹

Affiliations

¹ Department of Oral Physiology, Periodontal Diseases Signaling Network Research Center, Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan, Republic of Korea.
² Department of Oral Biochemistry, Pusan National University, Yangsan, Republic of Korea.
³ Department of Chemistry Education, Graduate Department of Chemical Materials, Institute for Plastic Information and Energy Materials, Sustainable Utilization of Photovoltaic Energy Research Center (ERC), Pusan National University, Busan, Republic of Korea.
⁴ School of Biomedical Convergence Engineering, Pusan National University, Yangsan, Republic of Korea.
⁵ Department of Physiology, University of Tennessee Health Science Center Memphis, Memphis, TN, USA.

Abstract

Background/purpose: Human dental pulp stem cells (hDPSCs) possess excellent proliferative and osteogenic differentiation potentials. This study aimed to elucidate the role of lysophosphatidic acid (LPA) signaling in the proliferation and osteogenic differentiation of hDPSCs.

Materials and methods: hDPSCs were treated with LPA and proliferation was measured using the cell counting kit-8 assay. Following the osteogenic differentiation of hDPSCs using osteogenic medium in the presence or absence of LPA, alkaline phosphatase (ALP) staining, ALP activity measurements, and RT-qPCR were performed to analyze the osteoblast differentiation. Small interfering RNA (siRNA)-mediated LPAR3 silencing and extracellular signal-regulated (ERK)/mitogen-activated protein (MAP) kinase inhibitors were used to elucidate the molecular mechanisms underlying LPA-induced proliferation and differentiation of hDPSCs.

Results: LPA treatment significantly induced proliferation and osteogenic differentiation of hDPSCs. The depletion of LPAR3 expression by LPAR3-speicifc siRNA in hDPSCs diminished LPA-induced proliferation and osteogenic differentiation. The LPAR3-mediated proliferation and osteogenic differentiation of hDPSCs in response to LPA were significantly suppressed by U0126, a selective inhibitor of ERK.

Conclusion: These findings suggest that LPA induces the proliferation and osteogenic differentiation of hDPSCs via LPAR3-ERK-dependent pathways.

Keywords: Human dental pulp stem cells; Lysophosphatidic acid; Osteogenic differentiation; Proliferation.