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  • Title: Recombinant human osteogenic protein-1 upregulates proteoglycan metabolism of human anulus fibrosus and nucleus pulposus cells.
    Author: Imai Y, Miyamoto K, An HS, Thonar EJ, Andersson GB, Masuda K.
    Journal: Spine (Phila Pa 1976); 2007 May 20; 32(12):1303-9; discussion 1310. PubMed ID: 17515818.
    Abstract:
    STUDY DESIGN: In vitro assessment of the effects of recombinant human osteogenic protein-1 (rhOP-1) on the proteoglycan metabolism of human intervertebral disc cells. OBJECTIVES: To determine whether rhOP-1 is effective in stimulating the cell proliferation and proteoglycan metabolism of human intervertebral disc cells cultured in alginate beads. SUMMARY OF THE BACKGROUND DATA: OP-1 has been shown to stimulate the proteoglycan and collagen synthesis of rabbit intervertebral disc cells in vitro. In vivo, a single injection of rhOP-1 restored the disc height of a degenerated disc in the rabbit anular-puncture model. The effect of rhOP-1 on human intervertebral disc cells remains unknown. METHODS: Human nucleus pulposus and anulus fibrosus cells were isolated from the discs of 4 cadaveric spines and one surgical specimen. After preculture for 7 days, alginate beads containing nucleus pulposus and anulus fibrosus cells were cultured for 21 days in media containing 10% fetal bovine serum with 0, 100, or 200 ng/mL rhOP-1 and supplements. The synthesis and accumulation of proteoglycans and the DNA content were biochemically assessed. RESULTS: The addition of rhOP-1 to the media resulted in the prevention of a decreased cell number during culture. Treatment with rhOP-1, compared with the control condition (10% fetal bovine serum), significantly upregulated proteoglycan synthesis and accumulation in alginate beads in all cases tested. A longer exposure over 14 days to rhOP-1 resulted in a pronounced response. The retention of newly-synthesized proteoglycan was higher in the rhOP-1-treated cells than in the control. CONCLUSIONS: rhOP-1 was effective in stimulating the cell proliferation and proteoglycan metabolism of human intervertebral disc cells in vitro. The results supported the hypothesis that an in vivo injection of rhOP-1 may increase the metabolic activity of disc cells or prevent apoptosis of disc cells in a degenerated disc. However, the requirement for a long exposure to rhOP-1 for human cells may suggest the need for a prolonged supply of rhOP-1 by a drug delivery system or by repeated injections.
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