Th17/IL‐17A Drives Alveolar Bone Loss via the JAK/STAT3‐RANKL Axis in the Periodontal Ligament

Objectives Th17 cells play a critical role in alveolar bone loss, which is closely associated with osteoclast maturation during periodontitis. Previous studies have established that periodontal ligament cells (PDLCs) are a significant source of receptor activator of nuclear factor‐κB ligand (RANKL), a pivotal osteoclast‐inducing cytokine. However, the mechanisms by which IL‐17A promotes osteoclast activation via the PDL‐mediated pathways are poorly understood. This study investigates how IL‐17A promotes RANKL production in PDLCs and evaluates the therapeutic potential of targeting the JAK/STAT3 pathway in periodontitis. Methods A ligature‐induced periodontitis (LIP) model was established and alveolar bone loss was assessed using micro‐CT and TRAP staining. The molecular mechanisms were investigated using bioinformatic analysis, western blotting, and immunohistochemistry. The efficacy of anti‐IL‐17A (αIL‐17A) and tofacitinib in inhibiting alveolar bone loss was evaluated through intraperitoneal injection. Results RANKL was predominantly expressed in the PDL during periodontitis. IL‐17A enhanced osteoclast activity in RAW264.7 cells co‐cultured with PDLCs. IL‐17A upregulated RANKL expression in PDLCs through STAT3 activation. Tofacitinib significantly inhibited alveolar bone loss by suppressing Th17 cell differentiation and osteoclast activation. Conclusions IL‐17A promoted RANKL expression through JAK/STAT3 activation in PDLCs. Tofacitinib, a clinically available JAK inhibitor, significantly attenuated alveolar bone loss in periodontitis.