Up-regulation of chondrocyte matrix genes and products by electric fields.
This study tested the hypothesis that selective and specific capacitively coupled electrical signals could stimulate gene expression and matrix production in bovine articular chondrocytes. Starting with a capacitively coupled electric signal that previously was shown to be effective in stimulating proliferation in bovine articular cartilage chondrocytes, dose responses were done sequentially for duration, response time, amplitude, duty cycle, and frequency. Results showed that a 0.5-hour, 20 mV/cm, signal at 60 kHz up-regulated aggrecan gene expression approximately eightfold (p < 0.0003) using a 50% duty cycle, whereas Type II collagen gene expression was up-regulated approximately fivefold (p < 0.02) using an 8.3% duty cycle. Using a compound signal (a 0.5-hour continuous period plus multiple 1-hour periods of 50% duty cycle for 7 days) both proteoglycan and collagen accumulation in vitro were increased approximately fivefold (p < 0.0003) and twofold (p < 0.0008), respectively. Also, the most effective capacitively coupled electric signal was different for each of the two molecules studied (aggrecan, 50% duty cycle and 4-hour response time; Type II collagen, 8.3% duty cycle and 6-hour response time). We conclude that selective up-regulation of gene expression and matrix accumulation of cartilage structural macromolecules (such as aggrecan and Type II collagen) with specific capacitively coupled fields occurs in vitro. This may be useful in vivo as a noninvasive modality to promote cartilage healing or ameliorate the effects of osteoarthritis, or both.
Department of Orthopaedic Surgery, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Wei
W
Wang
Zhenyu
Z
Wang
Guihong
G
Zhang
Charles C
CC
Clark
Carl T
CT
Brighton
D053674:Aggrecans; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D019902:Chondrocytes / Q000502:physiology* / Q000528:radiation effects*; D024043:Collagen Type II / Q000096:biosynthesis / Q000235:genetics*; D004574:Electromagnetic Fields; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis / Q000235:genetics*; D037181:Lectins, C-Type; D011509:Proteoglycans / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis; D015854:Up-Regulation / Q000528:radiation effects*
D053674:Aggrecans; D024043:Collagen Type II; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D011509:Proteoglycans; D012333:RNA, Messenger