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-1beta (IL-1beta) 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 <or= 0.005) of aggrecan and type-II collagen mRNA expression. This occurred even in the presence of IL-1beta. In the absence of IL-1beta, the expression of metalloproteinases was at barely detectable levels in these explants. Treatment with IL-1beta led to the significant upregulation of metalloproteinase 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-1beta, 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 metalloproteinase expression. These results support the contention that delivery of a specific, defined electrical field to articular cartilage could result in matrix preservation.
Brighton
Carl T
CT
McKay Laboratory of Orthopaedic Surgery Research, University of Pennsylvania School of Medicine, 424 Stemmler Hall, Philadelphia, PA 19104-6081, USA. ctb@mail.med.upenn.edu
Wang
Wei
W
Clark
Charles C
CC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002358:Cartilage, Articular / Q000378:metabolism* / Q000473:pathology; D002470:Cell Survival; D019902:Chondrocytes / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism*; D004558:Electric Stimulation; D005260:Female; D005269:Femur / Q000378:metabolism; D006595:Hexosamines / Q000378:metabolism*; D006801:Humans; D006909:Hydroxyproline / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D045726:Metalloproteases / Q000378:metabolism*; D008875:Middle Aged; D010003:Osteoarthritis / Q000378:metabolism* / Q000473:pathology; D016133:Polymerase Chain Reaction; D011897:Random Allocation; D013977:Tibia / Q000378:metabolism
D006595:Hexosamines; D003094:Collagen; D045726:Metalloproteases; D006909:Hydroxyproline