EFFECTS OF HYDROSTATIC-PRESSURE ON MATRIX SYNTHESIS AND MATRIX METALLOPROTEINASE PRODUCTION IN THE HUMAN LUMBAR INTERVERTEBRAL DISC

Study Design. This study is a unique in vitro study on the effects of hydrostatic pressure on human intervertebral disc metabolism. Objectiv e. To investigate the effects of hydrostatic pressure on matrix synthe sis and matrix metalloproteinase production in the human lumbar interv ertebral disc. Summary of Background Data. Mechanical stress and hydro static pressures influence proteoglycan and protein synthesis rates in bovine articular cartilage and coccygeal discs. However, the mechanis m of matrix synthesis regulation of the intervertebral disc under mech anical stress has not been elucidated. Methods. Twenty-eight human lum bar intervertebral discs obtained from surgery and from cadavers at au topsy were used. Each tissue fraction was charged with medium in a pla stic 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 syn thesis rates were determined by radioisotope incorporation. The produc tion of matrix metallaproteinase-3 and tissue inhibitor of metalloprot einases-1 were measured by a one-step enzyme immunoassay method using monoclonal antibodies. Results. Three atm pressure stimulated proteogl ycan synthesis rates in the nucleus pulposus and inner anulus (n = 14 in each tissue). Compared with the control group, 30 atm pressure sign ificantly inhibited proteoglycan synthesis in the inner anulus (P = 0. 011), In the nucleus pulposus, matrix metalloproteinase-3 production w as stimulated at a pressure of 30 atm relative to 3 atm (P = 0.014, n = 16 in each tissue). The highest tissue inhibitor of metalloproteinas es-1 production showed highest values at 3 atm pressure in the inner a nulus (n = 16 in each tissue). Conclusion. The results suggest that hy drostatic pressure influences intervertebral disc cell metabolism. A p hysiologic level of hydrostatic pressure (3 atm) may act as an anaboli c factor for stimulation of proteoglycan synthesis and tissue inhibito r of metalloproteinases-1 production. This may be essential for mainta ining the matrix of the disc. if the pressure was 30 atm or mote 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.