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A pulsing electric field (PEF) increases human chondrocyte proliferation through a transduction pathway involving nitric oxide signaling
Author(s) -
Fitzsimmons Robert J.,
Gordon Stephen L.,
Kronberg James,
Ganey Timothy,
Pilla Arthur A.
Publication year - 2008
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.20590
Subject(s) - nitric oxide , chondrocyte , calmodulin , chemistry , nitric oxide synthase , calcium , signal transduction , biophysics , microbiology and biotechnology , in vitro , biochemistry , biology , organic chemistry
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. © 2008 Orthopaedic Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:854–859, 2008