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Effects of Hydrostatic Pressure on Matrix Synthesis and Matrix Metalloproteinase Production in the Human Lumbar Intervertebral Disc

Handa, Tadashi, MD*; Ishihara, Hirokazu, MD*; Ohshima, Hiroshi, MD*; Osada, Ryusuke, MD*; Tsuji, Haruo, MD*; Obata, Ken'ichi, PhD

Basic Science

Study Design. This study is a unique in vitro study on the effects of hydrostatic pressure on human intervertebral disc metabolism.

Objective. To investigate the effects of hydrostatic pressure on matrix synthesis and matrix metalloproteinase production in the human lumbar intervertebral disc.

Summary of Background Data. Mechanical stress and hydrostatic pressures influence proteoglycan and protein synthesis rates in bovine articular cartilage and coccygeal discs. However, the mechanism of matrix synthesis regulation of the intervertebral disc under mechanical stress has not been elucidated.

Methods. Twenty-eight human lumbar intervertebral discs obtained from surgery and from cadavers at autopsy were used. Each tissue fraction was charged with medium in a plastic syringe and placed in a water-filled hydrostatic pressure-control vessel. The hydrostatic pressures applied were 1 (control), 3, and 30 atm (atm = atmospheres) for 2 hours. The proteoglycan and protein synthesis rates were determined by radioisotope incorporation. The production of matrix metalloproteinase-3 and tissue inhibitor of metalloproteinases-1 were measured by a one-step enzyme immunoassay method using monoclonal antibodies.

Results. Three atm pressure stimulated proteoglycan synthesis rates in the nucleus pulposus and inner anulus (n = 14 in each tissue). Compared with the control group, 30 atm pressure significantly inhibited proteoglycan synthesis in the inner anulus (P = 0.011). In the nucleus pulposus, matrix metalloproteinase-3 production was stimulated at a pressure of 30 atm relative to 3 atm (P = 0.014, n = 16 in each tissue). The highest tissue inhibitor of metalloproteinases-1 production showed highest values at 3 atm pressure in the inner anulus (n = 16 in each tissue).

Conclusion. The results suggest that hydrostatic pressure influences intervertebral disc cell metabolism. A physiologic level of hydrostatic pressure (3 atm) may act as an anabolic factor for stimulation of proteoglycan synthesis and tissue inhibitor of metalloproteinases-1 production. This may be essential for maintaining the matrix of the disc. If the pressure was 30 atm or more or 1 atm or less, a catabolic effect will be predominant, with reduction of proteoglycan synthesis rate and increase of matrix metalloproteinase-3 production. Abnormal hydrostatic pressure, therefore, may accelerate disc degeneration.

From the *Department of Orthopaedic Surgery, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan, and the †Biopharmaceutical Department, Fuji Chemical Industries, Ltd., Takaoka, Toyama, Japan.

Supported by a Grant-in-Aid for Scientific Research from The Japanese Ministry of Education, Science, and Culture, grant No. 05771061, 06771122 in 1993 and 1994.

Acknowledgment date: May 21, 1996.

First revision date: August 19, 1996.

Acceptance date: September 1, 1996.

Device status category: 1.

Address reprint requests to Hirokazu Ishihara, MD; Department of Orthopaedic Surgery; Faculty of Medicine; Toyama Medical and Pharmaceutical University; 2630 Sugitani; Toyama 930-01, Japan;

© 1997 by Lippincott Williams & Wilkins