The needle puncture approach, using 16G to 21G needles, resulted in a reproducible decrease of disc height and magnetic resonance imaging grade. The ease of the procedure and transfer of the methodology will benefit researchers studying disc degeneration.

PRP isolated from autologous blood may be useful as a source of anabolic growth factors for stimulating chondrocytes to engineer cartilage tissue.

The results of this study show the feasibility of restoring degenerative rabbit discs by a single injection of OP-1 into the nucleus pulposus. Importantly, the effects of the OP-1 injection on disc height were sustained for up to 24 weeks. The metabolic changes in the cells, following a single injection, might be sustained and, thus, induce long-term changes in disc structure. An efficacy study in large animals is required to show further that the intradiscal injection of OP-1, or bone morphogenetic proteins or growth factors with similar properties would be useful for the structural restoration of the IVD in humans.

Cells of the anulus fibrosus and nucleus pulposus react to tissue degeneration differently. Decreased mRNA expression by nucleus pulposus cells and declining protein content of the matrix make the nucleus more vulnerable to degeneration than the anulus. The cells in the anulus fibrosus respond to early degeneration by upregulating biosynthetic processes. However, in heavily degenerated tissues, the decline in the synthesis of aggrecan and the increase in the concentrations of small proteoglycans may be responsible for the failure of the repair processes.

Study Design-To characterize age-related changes in the matrix of human intervertebral disc specimens, human specimens from the 3 rd to the 8 th decade of life were collected and analyzed for collagen and proteoglycan composition.Objectives-To identify age-related changes in the concentration of matrix macromolecules (collagen and proteoglycans, including the small leucine-rich proteoglycans biglycan, decorin, fibromodulin and lumican) in human anulus fibrosus and nucleus pulposus.Summary of Background Data-Intervertebral disc degeneration is associated with changes in the concentration and fragmentation of matrix molecules. Deciphering age-related matrix alterations may help us to better understand the regulatory mechanisms underlying intervertebral disc degeneration.Methods-Forty-six whole intervertebral discs were obtained from the thoracolumbar spines (T11-L5) of humans aged between 32 and 80 years. All specimens were classified as Thompson Grade 1 or 2 according to MRI criteria. Specimens were separated into (i) outer-and (ii) inner anulus fibrosus as well as (iii) nucleus pulposus. DNA, collagen and proteoglycan contents were measured using chemical assays while small non-aggregating proteoglycan levels were analyzed by comparative Western blotting.Results-Total proteoglycan and collagen contents in both the anulus fibrosus and nucleus pulposus consistently decreased with aging. The concentrations of small non-aggregating proteoglycans varied. In the outer anulus, decorin levels decreased while biglycan and fibromodulin levels increased with age. In the inner anulus and nucleus, biglycan demonstrated a significant increase with aging. These changes differed in most cases from those previously reported for degenerating disc tissues.Conclusions-Collagen and proteoglycans appeared to undergo specific age-related changes in the human intervertebral disc. While the total contents of these two families of molecules decreased during aging, individual species of small non-aggregating proteoglycans showed species-specific age-related changes. Interestingly, the level of biglycan rose and remained elevated in all three NIH Public AccessAuthor Manuscript Spine (Phila Pa 1976 compartments of the disc with aging. The functional significance of these alterations is yet to be determined.

To date, no study has demonstrated the potential in vivo effects of growth factors on the intervertebral disc. The present study reports that the intradiscal administration of osteogenic protein-1 in vivo results in an increased disc height present at 2, 4, and 8 weeks and an increase in PG content of the nucleus pulposus at the 2-week time point. Therefore, osteogenic protein-1 may act to stimulate metabolic activity in the nucleus pulposus. Continued research is needed to evaluate the potential of growth factor-induced reversal of age-related disc degeneration in an appropriate animal model. In addition, studies in a nonhuman primate animal model will be essential before considering intradiscal injection of growth factors in humans.

This study was performed to determine if recombinant human osteogenic protein-] (rhOP-I) is effective in promoting matrix synthesis and matrix formation by rabbit nucleus pulposus (NP) and annulus fibrosus (AF) cells cultured in alginate beads. The effects of culturing the cells in the presence of various concentrations of rhOP-1 were assessed by measuring changes in cell proliferation, proteoglycan (PG) and collagen synthesis and mRNA expression, and in the matrix contents of PG and collagen, as indicators of matrix accumulation. At high concentrations, rhOP-l had a moderate mitogenic effect on both NP and A F cells. It also stimulated the synthesis of PG and collagen in a dose-dependent manner: this was associated with a corresponding increase in the expression of mRNA for aggrecan core protein and collagen type 11. The stimulatory effect of rhOP-1 on PG synthesis was more pronounced than that on collagen synthesis. Continuous treatment with rhOP-1 led to an increase in the total DNA, P G and collagen contents in both N P and A F cultures. The results presented here provide evidence of the ability of rhOP-l to stimulate the metabolism of both rabbit A F and N P cells cultured in alginate beads.

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