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<p>Rheumatoid arthritis (RA) is an autoimmune condition that involves inflammation of the joints, cartilage destruction, and progressive bone loss. RA is a disabling disease that may result in poor quality of life and permanent physical disability. Current interventions like NSAIDs, DMARDs, and biologics are more symptom-relieving and disease-preventing. But the increased risk of side effects, impaired immune system, and variability in efficacy restrict the efficacy and safety of such agents. The literature has brought to the forefront the pivotal role of Protease-activated receptors (PARs) in initiating inflammatory cascade, immune reactions, and progressive joint destruction. The main purpose of this review is to determine the potential of PAR inhibitors as an alternate treatment strategy for RA patients. <i>In-vitro</i> and <i>in-vivo</i> experiments have brought to the forefront the role of PAR inhibitors, like PAR-1 and PAR-2, in the modulation of bone cell activity, inhibition of cartilage destruction, and prevention of joint inflammation, and joint pain. Even though these observations are encouraging, we have yet to confirm the efficacy, safety, and specificity of PAR inhibitors. This review brings to the forefront the necessity to perform well-designed clinical trials with large sample sizes, to design specific and selective PAR inhibitors, and to explore the benefit of combination therapies in the treatment of RA.</p> Graphical abstract <p></p>

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Protease activated receptor inhibitors in rheumatoid arthritis: a new frontier in treatment

  • 期刊论文

  • 发表日期：

    2025年6月28日

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  • Tayyaba Rana,
  • Huma Hameed,
  • Ana Cláudia Paiva-Santos,
  • Muhammad Jamshaid,
  • Muneeba Anwar

摘要

Rheumatoid arthritis (RA) is an autoimmune condition that involves inflammation of the joints, cartilage destruction, and progressive bone loss. RA is a disabling disease that may result in poor quality of life and permanent physical disability. Current interventions like NSAIDs, DMARDs, and biologics are more symptom-relieving and disease-preventing. But the increased risk of side effects, impaired immune system, and variability in efficacy restrict the efficacy and safety of such agents. The literature has brought to the forefront the pivotal role of Protease-activated receptors (PARs) in initiating inflammatory cascade, immune reactions, and progressive joint destruction. The main purpose of this review is to determine the potential of PAR inhibitors as an alternate treatment strategy for RA patients. In-vitro and in-vivo experiments have brought to the forefront the role of PAR inhibitors, like PAR-1 and PAR-2, in the modulation of bone cell activity, inhibition of cartilage destruction, and prevention of joint inflammation, and joint pain. Even though these observations are encouraging, we have yet to confirm the efficacy, safety, and specificity of PAR inhibitors. This review brings to the forefront the necessity to perform well-designed clinical trials with large sample sizes, to design specific and selective PAR inhibitors, and to explore the benefit of combination therapies in the treatment of RA.

Graphical abstract