Growth Factor Osteogenic Protein-1

Objective: The objective of this study was to determine if cells isolated from three distinct zones in the bovine intervertebral disc (IVD) differ in their response to growth factor osteogenic protein-1 (OP-1) because of inherent biological differences. The new knowledge gained will help determine if treatment of degenerative disc disease with purified growth factors is effective and will provide guidance in terms of the injection technique and frequency of treatments required. Design: This was an in vitro study measuring the effects of OP-1 on proteoglycan accumulation and synthesis by cells from the nucleus pulposus, inner-annulus fibrosus (inner-AF), and outer-annulus fibrosus (outer-AF) in the bovine IVD. Results: Growth factor OP-1, at 100 ng/ml, stimulated proteoglycan accumulation and resulted in a statistically significant increase in the proteoglycan content of cells derived from three zones of the bovine IVD: 97% in the nucleus pulposus, 40% in the inner-AF, and 75% in the outer-AF. To elucidate the mechanism of enhanced proteoglycan accumulation in response to OP-1, we studied the rate of proteoglycan synthesis and cell proliferation. OP-1 stimulation resulted in a statistically significant increase in the DNA content in cultures containing cells from all three zones of the IVDs: 79% in the nucleus pulposus, 100% in the inner-AF, and 73% in the outer-AF. After dividing by DNA content, OP-1 resulted in a statistically significant increase in the rate of proteoglycan synthesis in the nucleus pulposus (78%) and outer-AF (17%) cells, but the increase in inner-AF cells (23%) did not achieve statistical significance. Conclusions: OP-1 stimulates proteoglycan accumulation by bovine IVD cells isolated from all three zones of the bovine IVDs. Cells from all three zones proliferated significantly. Individual cells derived from nucleus pulposus and outer-AF, but not those from the inner-AF, synthesized proteoglycans at a significantly faster rate with OP-1 stimulation.