Abstract
Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation of synovium (synovitis), with inflammatory/immune cells and resident fibroblast-like synoviocytes (FLS) acting as major players in the pathogenesis of this disease. The resulting inflammatory response poses considerable risks as loss of bone and cartilage progresses, destroying the joint surface, causing joint damage, joint failure, articular dysfunction, and pre-mature death if left untreated. At the cellular level, early changes in RA synovium include inflammatory cell infiltration, synovial hyperplasia, and stimulation of angiogenesis to the site of injury. Different angiogenic factors promote this disease, making the role of anti-angiogenic therapy a focus of RA treatment. To control angiogenesis, mesenchymal stromal cells/pericytes (MSCs) in synovial tissue play a vital role in tissue repair. While recent evidence reports that MSCs found in joint tissues can differentiate to repair damaged tissue, this repair function can be repressed by the inflammatory milieu. Extremely-low frequency pulsed electromagnetic field (PEMF), a biophysical form of stimulation, has an anti-inflammatory effect by causing differentiation of MSCs. PEMF has also been reported to increase the functional activity of MSCs to improve differentiation to chondrocytes and osteocytes. Moreover, PEMF has been demonstrated to accelerate cell differentiation, increase deposition of collagen, and potentially return vascular dysfunction back to homeostasis. The aim of this report is to review the effects of PEMF on MSC modulation of cytokines, growth factors, and angiogenesis, and describe its effect on MSC regeneration of synovial tissue to further understand its potential role in the treatment of RA.
Highlights
Rheumatoid arthritis (RA) is a systemic autoimmune disease affecting over 1.3 million Americans, and as much as 1% of the population worldwide [1]
In RA, pulsed electromagnetic field (PEMF) upregulates adenosine receptors to increase antiinflammatory effects on both chondrocytes and fibroblast-like synoviocytes (FLS) and reduces levels of enzymes produced by FLS and osteoclasts that lead to bone destruction [24, 27, 77] (Table 1)
mesenchymal stromal cells/pericytes (MSCs)/pericytes down-modulate the production of synovial macrophages, which trigger production of cytokines, such as IL-4, that initiate the proliferation of synovial fibroblasts, promoting the expression of growth factors such as vascular endothelial growth factor (VEGF) and TGF-β [138, 139]
Summary
Rheumatoid arthritis (RA) is a systemic autoimmune disease affecting over 1.3 million Americans, and as much as 1% of the population worldwide [1]. PEMF therapy is based on Faraday’s law, a basic law of electromagnetism that predicts how a magnetic field will interact with an electric circuit to produce an electromotive force known as electromagnetic induction This law dictates the more charge that is needed, the higher the intensity of the PEMF signal needs to be. Since the PEMF signal needs to be able to pass deep enough through the tissue to produce healing results, field intensity, frequency, and time of exposure are all important components in the dosimetry. Several studies have reported that PEMF can modulate both cell surface receptor expression/activation, and downstream signal transduction pathways, thereby restoring homeostatic cell functions such as viability, proliferation, differentiation, communication with neighboring cells, and interaction with components of the extracellular matrix (ECM) [18,19,20,21,22,23]. The beneficial effects of PEMF have been reported to last up to 3 months or longer in human patients with chronic inflammatory/autoimmune disorders [38] with no evidence of adverse effects [39]
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