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Upregulation of Intervertebral Disc-Cell Matrix Synthesis by Pulsed Electromagnetic Field Is Mediated by Bone Morphogenetic Proteins

Okada, Motohiro MD, PhD*,†; Kim, Jin Hwan MD*,†; Hutton, William C. DSc*,†; Yoon, Sangwook Tim MD, PhD*,†

doi: 10.1097/BSD.0b013e31823d36cf
Original Articles

Study Design: An in vitro study on the effects of pulsed electromagnetic field (PEMF) on intervertebral disc-cell matrix synthesis.

Objectives: The objective of the study was to determine whether (1) PEMF can upregulate intervertebral disc-cell matrix synthesis and (2) any upregulation obtained is through transforming growth factor (TGF)-β or bone morphogenetic proteins (BMPs).

Summary of Background Data: PEMF has been reported to produce cell proliferation, enhance cell function, and upregulate matrix synthesis in cell types such as osteoblasts, chondroblasts, endothelial cells, and fibroblasts through the upregulation of several growth factors. PEMF has been used clinically in the treatment of delayed bone union. However, PEMF has never been tested on human intervertebral disc cells.

Methods: The PEMF signal used was similar to that used in the clinical treatment of delayed fracture healing. Human disc cells were treated with PEMF for 8 hours per day for 3 days. Quantitative real-time polymerase chain reaction was performed to determine mRNA expression levels of aggrecan, collagen-2, TGF-β, BMP-2, and BMP-7. Sulfated glycosaminoglycan synthesis was analyzed using the dimethylmethylene blue (DMMB) method. Western blot analysis was performed to determine the protein levels of TGF-β, BMP-2, and BMP-7. To determine whether any action of PEMF was through BMP, recombinant human Noggin was used at a dose of 100 ng/mL to block BMP.

Results: PEMF could upregulate intervertebral disc-cell matrix synthesis. BMP-7 was markedly upregulated by PEMF and was upregulated much more than BMP-2. TGF-β was not upregulated by PEMF. The effect of PEMF on disc-cell matrix was entirely inhibited in the presence of Noggin.

Conclusions: PEMF acts through BMPs to upregulate intervertebral disc-cell matrix synthesis.

*Atlanta Veterans Affairs Medical Center, Decatur

Department of Orthopaedic Surgery, Emory University School of Medicine, Atlanta, GA

The authors declare no conflict of interest.

Reprints: Motohiro Okada, MD, Department of Orthopaedic Surgery, Wakayama Medical University, 811-1 Kimiidera, Wakayama City, Wakayama 641-8510, Japan (e-mail:

Received May 20, 2011

Accepted October 14, 2011

© 2013 Lippincott Williams & Wilkins, Inc.