Abstract

Periodontitis is the chronic inflammation of the periodontal tissue. The present study aimed to investigate the role of baricitinib, a Janus kinase (JAK)1/2 inhibitor, in periodontitis by using a lipopolysaccharide (LPS)-induced human periodontal ligament stem cell (PDLSC) model. The viability of PDLSCs stimulated by LPS was assessed in the presence of baricitinib by Cell Counting Kit-8 assay. The induction of oxidative stress was evaluated by detecting the intracellular reactive oxygen species (ROS) levels, superoxide dismutase (SOD) activity and glutathione (GSH) content. ELISA and reverse transcription-quantitative PCR were used to determine the levels of inflammatory factors TNF-α, IL-1β and IL-6. Alkaline phosphatase (ALP) activity and alizarin red staining were used to assess the osteogenic differentiation of PDLSCs. The expression levels of osteogenic differentiation- and JAK/signal transducer and activator of transcription (STAT) signaling-associated proteins were estimated with western blotting. RO8191, an agonist of the JAK/STAT pathway, was used to treat PDLSCs to investigate the regulatory mechanism of baricitinib. The results indicated that baricitinib elevated the LPS-induced decrease in cell viability. LPS-triggered oxidative stress and inflammation were inhibited by baricitinib, as demonstrated by the decreased levels of ROS, TNF-α, IL-1β, IL-6 and increased levels of SOD and GSH. In addition, baricitinib caused a marked elevation in ALP activity and mineralization ability of PDLSCs, as determined by the upregulated osteocalcin and Runt-related transcription factor 2 expression. Moreover, the expression levels of phosphorylated (p)-JAK1, p-JAK2 and p-STAT3 were downregulated by baricitinib in a dose-dependent manner. Furthermore, addition of RO8191 restored the effect of baricitinib on the induction of oxidative stress, inflammation and osteogenic differentiation of PDLSCs exposed to LPS.