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2024

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Nature Reviews Rheumatology | Liu Chuanju Team Depth Analysis of Ion Channels: New Hope for Osteoarthritis Treatment

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Osteoarthritis (OA) is a common joint disease characterized by joint pain and disability. Due to the lack of effective preventive measures or treatments that can delay the progression of OA, this disease not only seriously affects the quality of life of patients, but also brings a huge economic burden. Ion channels are located on the cell membrane.porinThe ion balance, membrane potential and cell volume of cells are maintained by regulating the flow of ions.Studies have shown that the abnormal expression or dysfunction of ion channels is one of the important reasons for the progression of OA.An in-depth understanding of how ion channels affect gene expression and signaling in joint cells is essential for exploring effective treatments for OA.Increasing evidence suggests that ion channels are not only key mediators in the pathogenesis of OA, but also potential targets for mitigating disease progression in OA.

Yale University School of MedicineLiu ChuanjuThe Professor team is invitedNature Reviews Rheumatology（IF=29.4）The magazine is entitled"Ion channels in osteoarthritis: emerging roles and potential targets"Review article. The article was published online on August 9, 2024. This review systematically discusses the structure and function of a variety of ion channels, including transient receptor potential channel (TRP), Piezo channel, voltage-gated sodium channel (Nav), voltage-dependent calcium channel (Cav), potassium channel (K+), acid-sensitive ion channel (ASIC), chloride ion channel (Cl-) and the role of P2X receptors in OA and their underlying molecular mechanisms.This review comprehensively addresses the important contributions of ion channels in the pathophysiology of OA and highlights the potential of targeted regulation of ion channels in the treatment of OA.Therapeutic strategies targeting ion channels are complex and require an in-depth understanding of the biology and pathophysiology of ion channels.This review highlights the clinical implications of further exploration of ion channels in OA and the potential new opportunities for targeted ion channel intervention.

With the aging of the population, the treatment of OA is facing great challenges. Current pharmacologic and non-pharmacologic interventions focus on symptom relief, but these often provide only partial relief and are associated with significant side effects.Therefore, there is an urgent need to develop more effective and safer treatments that target the underlying mechanisms of OA.

This review explores the potential of ion channels as therapeutic targets in the multifaceted nature of OA pathology and associated pain. A detailed overview of the key regulatory roles of ion channels in normal and OA articular cells, such as osmotic regulation, mechanotransduction, chemical transduction and metabolic functions in chondrocytes. Abnormal expression or deregulation of ion channels can accelerate the progression of OA, and a large number of evidences show that they are closely related to synovial hyperplasia, cartilage destruction, endochondral ossification, inflammatory reaction and pain. This article describes the structure and function of various ion channels and their roles and potential mechanisms in gene expression and signal transduction in joint cells. In addition, ion channels affect the inflammatory response and associated pain by regulating the release of pro-and anti-inflammatory factors. The article also summarizes the progress of clinical trials of ion channel modulators in the treatment of OA, pointing out that most of the trials mainly focus on the study of the effects of agonists or antagonists on knee pain, and pay less attention to the evaluation of cartilage degradation, local inflammation or other weight-bearing joints (such as hip and ankle joints).Although the role of ion channels in OA has been well understood, there are still many unknown areas that need to be further explored.An in-depth study of the electrophysiological properties and interaction mechanisms of ion channels in joint cells and the development of specific modulators are essential for the development of effective and safe treatments for OA. Future therapeutic strategies may include innovative approaches such as small molecule drugs, gene therapy, local injections and biomaterials to improve efficacy and reduce side effects.

This review not only provides a new perspective for our understanding of the complex mechanisms of OA, but also provides important guidance for the development of novel therapeutic approaches. Although targeted ion channel therapy for OA is still in its infancy, it brings new hope and possibilities for more effective and targeted OA management interventions and innovative treatment strategies in the future.
Dr. Renpeng Zhou of Yale University School of Medicine is the first author of this article, and Professor Liu Chuanju of Yale University School of Medicine (Charles W. Ohse Endowed Chair Professor) is the corresponding author of this article.

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Wu Haitao of Nantong University and Chu Bo of Shandong University have shown that the development and survival of cerebellar Purkinje cells are regulated by iron death!

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Cell sub-journal | Lu Yan of Shanghai Jiaotong University and other teams have jointly revealed the important role of deubiquitinating enzyme RPN11 in improving nonalcoholic fatty liver disease!

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