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JAK Inhibitor Tofacitinib Ameliorates Inflammation Response and Osteogenic Differentiation in Immune-Mediated

Zhiming Zhang1, Zhiming Lin2, Genlian Hu3

  • 1Department of Rheumatology and Immunology, The Second Affiliated Hospital of Fujian Traditional Chinese Medical University, Fuzhou, Fujian, China.

International Journal of Rheumatic Diseases
|July 15, 2026
PubMed
Abstract

Insights

Tofacitinib reduces inflammation and bone formation in arthritis by inhibiting the JAK/STAT3 pathway. This study in rats shows tofacitinib

Area of Science:

  • Immunology
  • Rheumatology
  • Cell Biology

Background:

  • Immune-mediated inflammatory arthritis involves complex inflammatory responses and aberrant osteogenic differentiation.
  • The Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) signaling pathway is implicated in inflammatory and bone remodeling processes.
  • Understanding the role of JAK/STAT3 in arthritis pathogenesis is crucial for developing targeted therapies.

Purpose of the Study:

  • To investigate the mechanism of tofacitinib in modulating inflammatory responses and osteogenic differentiation in a rat model of immune-mediated inflammatory arthritis.
  • To elucidate the involvement of the Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) signaling pathway in tofacitinib's effects.

Main Methods:

  • An immune-mediated inflammatory arthritis rat model was established using bovine proteoglycan and Freund's adjuvant.
  • Clinical, pathological, and molecular markers were assessed, including inflammatory factors, Th17 cell proportion, alkaline phosphatase (ALP) activity, and osteogenic differentiation markers.
  • The JAK/STAT3 signaling pathway activation and the effect of tofacitinib, alone and with a STAT3 agonist (Colivelin), were analyzed.

Main Results:

  • Tofacitinib treatment significantly reduced joint swelling, inflammation, cartilage destruction, and pro-inflammatory cytokine levels in arthritic rats.
  • Tofacitinib inhibited JAK/STAT3 phosphorylation, decreased osteogenic differentiation markers, alkaline phosphatase activity, and mineralized nodule formation.
  • Partial reversal of tofacitinib's effects was observed when co-administered with a STAT3 agonist, suggesting pathway-specific action.

Conclusions:

  • Tofacitinib effectively alleviates inflammatory responses in immune-mediated inflammatory arthritis.
  • Tofacitinib inhibits osteogenic differentiation in this arthritis model.
  • These therapeutic effects are mediated through the inhibition of the JAK/STAT3 signaling pathway.
Keywords:
JAK/STAT3 signaling pathwayinflammatory disorderinflammatory responseosteogenic differentiationtofacitinib

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