Rheumatoid arthritis (RA) is a chronic disease of joints that is characterized by inflammation, abnormal cellular and humoral immune responses, and synovial hyperplasia. Mast cells (MCs) are involved in several of these inflammatory and immune events. MC-derived mediators induce edema, destroy connective tissue, and are involved in lymphocyte chemotaxis and infiltration and in pathological fibrosis of RA joints. Moreover, MCs are involved in angiogenesis during RA, and their proteolytic activity results in cartilage destruction and bone remodeling. Lastly, MCs could be a target in the treatment of RA.

Angiogenesis is a multistep process driven by a wide range of positive and negative regulatory factors. Extracellular matrix (ECM) plays a crucial role in the regulation of this process. The degradation of ECM, occurring in response to an angiogenic stimulus, leads to degradation or partial modification of matrix molecules, release of soluble factors, and exposure of cryptic sites with pro- and/or antiangiogenic activity. ECM molecules and fragments, resulting from proteolysis, can also act directly as inflammatory stimuli, and this can explain the exacerbated angiogenesis that drives and maintains several inflammatory diseases. In this review we have summarized some of the more recent literature data concerning the molecular control of ECM in angiogenesis in both physiological and pathological conditions.

Evidence of the role of vitamin D in the regulation of T and B cells, macrophages, dendritic cells, and keratinocytes continues to accumulate and provides a link between vitamin D and many autoimmune diseases, including Crohn's disease, juvenile diabetes mellitus, multiple sclerosis, asthma, and rheumatoid arthritis. Considering the influence of vitamin D on the immune system, it may have potential as a treatment for immune-mediated diseases, even if additional research is required to better quantify dosage. But the biggest obstacle to its clinical use is its potent hypercalcemic effect. The calcium status of the host may influence the effect of vitamin D on immunity.

Even if osteoarthritis pathogenesis is still poorly understood, numerous evidences suggest that osteoblasts dysregulation plays a key role in osteoarthritis pathogenesis. An abnormal expression of OPG and RANKL has been described in osteoarthritis osteoblasts, which is responsible for abnormal bone remodeling and decreased mineralization. Alterations in genes expression are involved in dysregulation of osteoblast function, bone remodeling, and mineralization, leading to osteoarthritis development. Moreover, osteoblasts produce numerous transcription factors, growth factors, and other proteic molecules which are involved in osteoarthritis pathogenesis.

Considering that osteoblasts may be involved in bone disorders, such as osteoporosis, osteopetrosis, osteogenesis imperfecta, and Paget's disease, and that bisphosphonates may stimulate proliferation of osteoblasts and inhibit apoptosis of osteocytes and osteoblasts, it is conceivable that a role for bisphosphonates exists in these diseases beyond merely the osteoclast influence.