The Pros1/Tyro3 axis protects against periodontitis by modulating STAT/SOCS signalling

Area of Science:

• Oral Biology
• Immunology
• Pharmacology

Background:

• Periodontitis is a prevalent chronic inflammatory disease with significant healthcare costs.
• TAM receptor tyrosine kinases and their ligands, including Pros1, are crucial for resolving inflammation and are implicated in chronic diseases.

Purpose of the Study:

• To investigate the therapeutic potential of exogenous Pros1 in periodontitis models.
• To elucidate the mechanisms underlying Pros1's effects on periodontitis.

Main Methods:

• Analysis of Pros1 and Tyro3 levels in human gingival specimens.
• In vitro studies using human gingival epithelial cells stimulated with Porphyromonas gingivalis LPS.
• In vivo studies in a rat model of periodontitis.
• Assays included PCR, Western blot, ELISA, and gelatin zymography.

Main Results:

• Periodontitis patients exhibited higher Pros1 and lower Tyro3 levels in gingival tissues.
• Exogenous Pros1 inhibited inflammatory cytokine and matrix metalloproteinase production in vitro in a Tyro3-dependent manner.
• Pros1 treatment reduced gingival inflammation and alveolar bone loss in a rat model.
• Mechanistic studies identified SOCS1/3 and STAT1/3 as mediators of Pros1's anti-inflammatory effects.

Conclusions:

• Pros1 demonstrates significant anti-inflammatory and protective effects in both in vitro and in vivo periodontitis models.
• Pros1 acts through Tyro3, SOCS1/3, and STAT1/3 pathways to mitigate periodontitis.
• Pros1 represents a potential novel therapeutic agent for periodontitis.