Calcium signaling dysregulation in rheumatoid arthritis: a comparative perspective with osteoarthritis

Rheumatoid arthritis and osteoarthritis are among the most prevalent chronic diseases worldwide, imposing a significant burden on both patients and healthcare systems. Despite their distinct etiology and progression, emerging evidence suggests that calcium signaling plays a pivotal role in the pathogenesis of both diseases by influencing a variety of cellular processes within joint tissues. Calcium is essential for regulating key cellular functions, including gene expression, muscle contraction, cell cycle progression, proliferation, apoptosis, excitation-contraction coupling, synaptic transmission, and embryonic development. Particularly, in the context of arthritic diseases, an imbalance in calcium homeostasis has significant consequences, since the osteogenic and chondrogenic processes, as well as extracellular matrix formation, are highly influenced by calcium levels. Given these insights, a deeper understanding of the mechanisms governing calcium uptake, release, and metabolism could enhance our comprehension of disease pathogenesis and facilitate the development of novel therapeutic strategies. This review provides an overview of calcium signaling mechanisms, particularly in the most affected cells and tissues in rheumatoid arthritis and osteoarthritis, and summarizes the emerging therapies targeting calcium metabolism that may improve current treatment options.