Baricitinib alleviates lipopolysaccharide‑induced human periodontal ligament stem cell injury and promotes osteogenic differentiation by inhibiting JAK/STAT signaling

Yang,Ping; Shi,Fenghua; Zhang,Yanli

doi:10.3892/etm.2022.11773

Baricitinib alleviates lipopolysaccharide‑induced human periodontal ligament stem cell injury and promotes osteogenic differentiation by inhibiting JAK/STAT signaling

Authors:
- Ping Yang
- Fenghua Shi
- Yanli Zhang
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Affiliations: Department of Stomatology, AnTing Campus, The Third Affiliated Hospital of Naval Military Medical University, Shanghai 200438, P.R. China, Department of Radiotherapy, AnTing Campus, The Third Affiliated Hospital of Naval Military Medical University, Shanghai 201805, P.R. China, Outpatient Department, ChangHai Road Campus, The Third Affiliated Hospital of Naval Military Medical University, Shanghai 200438, P.R. China
Published online on: December 22, 2022 https://doi.org/10.3892/etm.2022.11773
Article Number: 74
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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. Collectively, these findings suggested that baricitinib alleviated oxidative stress and inflammation and promoted osteogenic differentiation of LPS‑induced PDLSCs by inhibiting JAK/STAT signaling.

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