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

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.

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.

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.

IL-17A promoted RANKL expression through JAK/STAT3 activation in PDLCs. Tofacitinib, a clinically available JAK inhibitor, significantly attenuated alveolar bone loss in periodontitis.