RA is a chronic autoimmune disease characterized by synovial inflammation and joint damage, driven by autoantibodies such as ACPA, anti-CarP and RF. These autoantibodies, influenced by genetic and environmental factors, play a crucial role in RA pathogenesis through post-translational modifications like citrullination, carbamylation, and acetylation. The early detection of ACPA provides a potential window for intervention, while anti-CarP antibodies correlate with severe disease progression and RF aids in diagnosis. Translating these findings from human pathology to animal models presents significant challenges. Although the presence of adaptative immune cells (T cells) is well defined in animal models of RA, studies yield inconsistent results regarding autoantibody production and implication in the disease onset and progression, with varying detectability of ACPA, anti-CarP antibodies, and RF across different species and models. The collagen-induced arthritis (CIA) model shows PAD4 expression and citrullinated protein presence but inconsistent ACPA detection, while the K/BxN model elucidates the pathogenicity of anti-GPI autoantibodies and implicates Fcγ receptors in disease processes. Therefore, further research is needed to bridge the gap between animal models and human RA pathology. Future studies should focus on developing more representative animal models, exploring pharmacological targets and pathways that involve the interplay between anti-inflammatory and autoimmune responses, and investigating the complex interplay between genetic predisposition, environmental triggers, and autoimmune mechanisms. This approach may lead to improved early diagnostic tools, targeted therapies, and potentially preventive strategies for RA, ultimately enhancing patient outcomes and quality of life.

The purinergic system has a dual role: the maintenance of energy balance and signaling within cells. Adenosine and adenosine triphosphate (ATP) are essential for maintaining these functions. Sarcopenia is characterized by alterations in the control of energy and signaling in favor of catabolic pathways. This review details the association between the purinergic system and muscle and adipose tissue homeostasis, discussing recent findings in the involvement of purinergic receptors in muscle wasting and advances in the use of the purinergic system as a novel therapeutic target in the management of sarcopenia.

Objective: Rheumatoid sarcopenia, characterized by the progressive loss of skeletal muscle mass and function, is a frequent comorbidity in rheumatoid arthritis (RA), linked to prolonged, severe systemic inflammation. Purinergic signaling (adenosine, AMP, and ATP) plays a crucial role in inflammation, myogenesis, and muscle hypertrophy. Dipyridamole, an antiplatelet agent, enhances extracellular adenosine availability, alters AMP/ATP ratio, and activates A2BR and AMP kinase (AMPK) pathways. We aim to investigate its potential use as a therapeutic agent for RA and rheumatoid sarcopenia. Methods: K/BxN‐induced mice received preventive or therapeutic dipyridamole treatment daily and were sacrificed at joint inflammation peak and resolution stage. Motor activity tests and dual‐energy x‐ray absorptiometry were performed. C‐reactive protein levels were also analyzed in serum, and cytokines array was performed in serum and muscle. Histology of tibialis anterior and talus joint were studied. Myogenesis, purinergic system, atrophy, and senescence key markers were analyzed via Western blot and reverse transcriptase–polymerase chain reaction in gastrocnemius. Nucleotide content via high‐performance liquid chromatography was performed. Two‐dimensional and three‐dimensional models with C2C12 cells were done. Results: Dipyridamole reduced joint, muscle, and systemic inflammation, counteracting muscle wasting and physical inactivity via an anabolic mechanism involving down‐regulation of myostatin expression. This effect was mediated by increased adenosine and AMP levels, which activate adenosine A2BR and downstream cAMP/AMPK signaling pathways. Conclusion: These results support a dual role for dipyridamole in RA, combining robust anti‐inflammatory effects with a novel, myostatin‐linked anabolic action on sarcopenia, mediated through adenosine and AMPK signaling, distinct from conventional therapeutic mechanisms. image