Lidocaine intensifies the anti-osteogenic effect on inflammation-induced human dental pulp stem cells via mitogen-activated protein kinase inhibition

Sang-Hoon Lee; Cheul-Hong Kim; Ji-Young Yoon; Eun-Ji Choi; Mi Kyoung Kim; Ji-Uk Yoon; Hee Young Kim; Eun-Jung Kim

doi:10.1016/j.jds.2022.11.020

Lidocaine intensifies the anti-osteogenic effect on inflammation-induced human dental pulp stem cells via mitogen-activated protein kinase inhibition

J Dent Sci. 2023 Jul;18(3):1062-1072. doi: 10.1016/j.jds.2022.11.020. Epub 2022 Dec 1.

Authors

Sang-Hoon Lee¹, Cheul-Hong Kim¹, Ji-Young Yoon¹, Eun-Ji Choi¹, Mi Kyoung Kim², Ji-Uk Yoon³, Hee Young Kim³, Eun-Jung Kim¹

Affiliations

¹ Department of Dental Anesthesia and Pain Medicine, School of Dentistry, Pusan National University, Dental Research Institute, Yangsan, Republic of Korea.
² Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan, Republic of Korea.
³ Department of Anesthesia and Pain Medicine, School of Medicine, Pusan National University, Yangsan, Republic of Korea.

Abstract

Background/purpose: Human dental pulp stem cells (hDPSCs) are an emerging source of mesenchymal stem cells (MSCs) for bone tissue regeneration and engineering. In bone regeneration using transplanted MSCs, the extracellular environment or co-injected drugs can affect their success or failure. In this study, we investigated the effects and signaling mechanisms of lidocaine on osteogenic differentiation of hDPSCs after inducing inflammatory conditions with lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF-α).

Materials and methods: To investigate the effect of lidocaine on the osteogenic differentiation of LPS/TNF-α-treated hDPSCs, alkaline phosphatase (ALP) and Alizarin red S (ARS) staining were conducted. The expression of osteogenesis-related genes was assessed using quantitative real-time polymerase chain reaction and western blotting. The expression of mitogen-activated protein kinases was analyzed to evaluate the effect of lidocaine on osteogenic differentiation of LPS/TNF-α-treated hDPSCs.

Results: Various concentrations of lidocaine (0.05, 0.2, and 1 mM) further decreased ALP and ARS staining of LPS/TNF-α-treated hDPSCs. Similarly, the mRNA and protein expression of osteogenesis-related genes was suppressed via lidocaine treatment in LPS/TNF-α-treated hDPSCs. Lidocaine treatment downregulated the protein expression of p-ERK and p-JNK in LPS/TNF-α-treated hDPSCs.

Conclusion: Lidocaine intensified the inhibition of osteogenic differentiation on inflammation-induced hDPSCs by inhibiting the ERK and JNK signaling pathways. This in vitro study suggested that lidocaine may have an inhibitory effect on bone regeneration.

Keywords: Dental pulp stem cell; Inflammation; Lidocaine; Mitogen-activated protein kinases; Osteogenic differentiation.