Background/purposeHuman 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 methodsTo 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.ResultsVarious 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.ConclusionLidocaine 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.