The effect of electrical fields on gene and protein expression in human osteoarthritic cartilage explants

Background: The destruction of cartilage in patients with osteoarthritis is a consequence of an imbalance between matrix synthesis and degradation. The purpose of the present study was to determine the effects of electrical stimulation on these processes in full-thickness osteoarthritic adult human articular cartilage explants. Methods: Full-thickness articular cartilage explants from osteoarthritic adult human knee joints were cultured in the absence or presence of interleukin-1 beta (IL-1 beta) and in the absence or presence of a specifically defined capacitively coupled electrical signal for seven or fourteen days. Total collagen and proteoglycan production were assessed by means of hydroxyproline and hexosamine analyses, respectively. Quantitative real-time polymerase chain reaction assays were used to measure mRNA expression levels of aggrecan, type-II collagen, collagenase-1 (MMP-1), collagenase-3 (MMP-13), stromelysin-1 (MMP-3), aggrecanase-1 (ADAM-TS4), and aggrecanase-2 (ADAM-TS5). Results: Electrical stimulation of cultured explants for seven or fourteen days resulted in significant increases (p < 0.007) in proteoglycan and collagen production and a highly significant upregulation (p <= 0.005) of aggrecan and type-II collagen mRNA expression. This occurred even in the presence of IL-1 beta. In the absence of IL-1 beta, the expression of metalloproteinases was at barely detectable levels in these explants. Treatment with IL-1 beta led to the significant upregulation of metal loproteinase expression (p < 0.03), but simultaneous administration of the capacitively coupled electrical signal dramatically inhibited this stimulation. Conclusions: The data show that, even in the presence of IL-1 beta, a specific, defined capacitively coupled electrical signal can result in significant upregulation of cartilage matrix protein expression and production while simultaneously significantly attenuating the upregulation of metal loproteinase expression. These results support the contention that delivery of a specific, defined electrical field to articular cartilage could result in matrix preservation. Clinical Relevance: Osteoarthritis ultimately results in the progressive destruction of articular cartilage through mechanisms involving metalloproteinase activity. The use of electrical stimulation to both increase matrix production and diminish matrix destruction has the promising potential to treat osteoarthritic patients in a noninvasive manner.