Fibronectin and its fragments increase with degeneration in the human intervertebral disc

Study Design. This laboratory-based experiment correlates fibronectin conte nt of intervertebral disc with a morphologic grade of degeneration. Objectives. To correlate the fibronectin content of the anulus fibrosus and nucleus pulposus with a gross morphologic grade of disc degeneration, and to determine the molecular size of the extractable fibronectin. Summary of Background Data. Intervertebral disc degeneration increases with age and can lead to low back pain. Fibronectin helps to organize the extra cellular matrix and provides environmental cues by interaction with cell su rface integrins. In other tissues, its synthesis is elevated in response to injury. Fibronectin fragments can stimulate cells to produce metalloprotea ses and cytokines and inhibit matrix synthesis. Methods. In this study, 17 anuli fibrosis and 18 nuclei pulposus from 11 sp ines were graded by Thompson's gross morphologic scale. Fibronectin was seq uentially extracted with 4 mol/L guanidine hydrochloride and trypsin, and t hen quantitated by enzyme-linked immunoassay. The size of extractable fibro nectin was determined by Western blot analyses. Results. The fibronectin content of the disc increased with grade and was s ignificantly elevated between Grades 3 and 4. The percentage of extractable fibronectin varied widely, but it was more extractable from the nucleus. I n both the nucleus and anulus, 30% to 40% of the extractable fibronectin ex isted as fragments. Many of the fragments contained functional heparin or c ollagen-binding sites. Conclusions. Fibronectin is elevated in degenerated discs and frequently pr esent as fragments. Elevated levels of fibronectin suggest that disc cells are responding to the altered environment. Fibronectin fragments resulting from;normal or enhanced proteolytic activity could be a mechanism that indu ces the cell to degrade the matrix further.