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.

Adenosine regulates multiple physiological processes through the activation of four receptor subtypes, of which the A_2B adenosine receptor (A_2BAR) has the lowest affinity for adenosine. Being the adenosine receptor subtype most prominently expressed in epidermis, we recently described the antiproliferative and anti-inflammatory effect of the selective A_2BAR agonist BAY60-6583 (BAY) in human keratinocytes stimulated with 12-O-tetradecanoylphorbol-13-acetate (TPA), so we sought to establish the effect of topical application of BAY in a model of murine epidermal hyperplasia. Topical application of BAY (1 or 10 μg/site) prevented the inflammatory reaction and skin lesions induced by TPA, minimizing hyperproliferation and acanthosis, as well as the expression of specific markers of proliferative keratinocytes. On the other hand, pre-treatment with the selective A_2BAR antagonist, PSB-1115 (PSB, 5 or 50 μg/site) reversed these beneficial effects. Additionally, BAY application normalized the expression of epidermal barrier proteins, whose integrity is altered in inflammatory skin diseases, while treatment with the antagonist alone worsened it. Our results, besides confirming the anti-inflammatory and antiproliferative effects of the A2BAR agonist, further demonstrate a role of A_2BAR activation to preserve the epidermal barrier. Therefore, the activation of A_2BAR may constitute a possible new pharmacological target for the treatment of skin inflammatory diseases such as psoriasis.

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.

Osteoarthritis (OA) is characterized by a loss of the joint viscoelastic properties. Hyaluronic acid (HA) intraarticular injections restore viscoelasticity, alleviating pain and improving patient function. Larger amounts of HA in a single injection could lead to greater efficacy, although the mechanism responsible for the long-term analgesic effect remains uncertain. We evaluated the effect of high concentrations of intra-articular HA on the innate immune response in synovial tissue in experimental OA and in cultured ATDC5 chondrocytes. Experimental OA was induced by destabilization surgery in the right knee of the rabbits. Four weeks after surgery, some rabbits received weekly intra-articular injections of 0.5 mL of 2% hyaluronic acid (HA, as commercially available formulation Adant Plus) for three weeks, while others received saline (vehicle). Eight weeks after surgery, right tibias, femurs, and synovial membranes were isolated for histopathology and molecular biology studies. In addition, the effect of 0.2% and 0.1% concentrations of HA on chondrocyte viability and oxidative stress was analyzed using ATDC5 chondrocytes in culture. 2% HA did not alter cartilage or synovial damage, although it demonstrated a good safety profile. 2% HA administration reduced IL-1β protein synthesis in the synovial membrane of OA rabbits. In cultured ATDC5 chondrocytes, 0.1% and 0.2% HA partially counteracted the deleterious effects of H₂O₂ on the gene expression of superoxide dismutase (SOD)-1 and heme oxygenase (HMOX)-1. Intra-articular administration of high concentrations of HA reduced IL-1β concentration in the OA synovium despite no observable improvement in cartilage or synovial lesions was observed. We suggest that the long-term beneficial effect of HA in human OA could be attributed to a "memory fingerprint" in the innate immune response, potentially leading to sustained reduced activity over an extended period of treatment.