A pulsing electric field (PEF) increases human chondrocyte proliferation through a transduction pathway involving nitric oxide signaling.
A potential treatment modality for joint pain due to cartilage degradation is electromagnetic fields (EMF) that can be delivered, noninvasively, to chondrocytes buried within cartilage. A pulsed EMF in clinical use for recalcitrant bone fracture healing has been modified to be delivered as a pulsed electric field (PEF) through capacitive coupling. It was the objective of this study to determine whether the PEF signal could have a direct effect on chondrocytes in vitro. This study shows that a 30-min PEF treatment can increase DNA content of chondrocyte monolayer by approximately 150% at 72 h poststimulus. Studies intended to explore the biological mechanism showed this PEF signal increased nitric oxide measured in culture medium and cGMP measured in cell extract within the 30-min exposure period. Increasing calcium in the culture media or adding the calcium ionophore A23187, without PEF treatment, also significantly increased short-term nitric oxide production. The inhibitor W7, which blocks calcium/calmodulin, prevented the PEF-stimulated increase in both nitric oxide and cGMP. The inhibitor L-NAME, which blocks nitric oxide synthase, prevented the PEF-stimulated increase in nitric oxide, cGMP, and DNA content. An inhibitor of guanylate cyclase (LY83583) blocked the PEF-stimulated increase in cGMP and DNA content. A nitric oxide donor, when present for only 30 min, increased DNA content 72 h later. Taken together, these results suggest the transduction pathway for PEF-stimulated chondrocyte proliferation involves nitric oxide and the production of nitric oxide may be the result of a cascade that involves calcium, calmodulin, and cGMP production.
Fitzsimmons
Robert J
RJ
The Technical Basis LLC, 24769 Redlands Blvd, Suite E, Loma Linda, California 92354, USA. biocore1@aol.com
Gordon
Stephen L
SL
Kronberg
James
J
Ganey
Timothy
T
Pilla
Arthur A
AA
D000634:Aminoquinolines / Q000494:pharmacology; D002455:Cell Division / Q000502:physiology / Q000528:radiation effects; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D006152:Cyclic GMP / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004558:Electric Stimulation; D004574:Electromagnetic Fields; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects*
D000634:Aminoquinolines; D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D009599:Nitroprusside; D009569:Nitric Oxide; D004247:DNA; C041715:6-anilino-5,8-quinolinedione; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester