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EXPERIMENTAL CHEMONUCLEOLYSIS WITH RECOMBINANT HUMAN MATRIX PROTEINASE‐7: O12

Haro, H; Takenouchi, O; Kato, T; Koyanagi, S; Komori, H

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Spine Journal Meeting Abstracts: 2015 - Volume 2015 - Issue - p 21
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INTRODUCTION: Chemonucleolysis has been proposed as a less invasive technique than surgery for patients with lumbar disc herniation. The purpose of this study was to investigate the effects of recombinant human matrix metalloproteinase 7 (rhMMP‐7) in experimental chemonucleolysis in vitro and in vivo and to examine its effects on tissue damage. METHODS: The effects of rhMMP‐7 on the degradation of human herniated discs (HD) were examined by measuring the wet weight in vitro. The correlations between the decrease in wet weight by rhMMP‐7 and the conditions associated with HD were also analyzed. The effects of rhMMP‐7 on the proteoglycan and water content were respectively examined with alcian blue staining and T2‐weighted MRI at 7 days after intradiscal injection in dogs. The distribution of [125I]‐labeled rhMMP‐7 was investigated by autoradioluminography at 7 days after intradiscal injection in dogs. An epidural injection study with rhMMP‐7 was performed to evaluate the effects on the tissue damage around the discs at 1 and 13 weeks after the treatment in dogs. The type 1 and 2 collagen cleavage rates were measured and compared with that of aggrecan in vitro. RESULTS: Rh MMP‐7 concentration‐dependently decreased the wet weight of HD in vitro. The decrease in wet weight didn't significantly correlate with the HD conditions. Intradiscal injection of rhMMP‐7 reduced the proteoglycan content and water content, with an increase in the serum keratan sulfate. Radioactivity of [125I]‐labeled rhMMP‐7 was detected in the disc, but not in the muscle. Epidural injection of rhMMP‐7 had no effect on the injection site or the nerve tissues. CONCLUSIONS: The effects of rhMMP‐7 were not affected by the conditions associated with HD. The epidural injection study suggests that intradiscal injection of rhMMP‐7 may not induce tissue damage around the discs because of its distribution and substrate selectivity. Recombinant human MMP‐7 may be a novel and promising chemonucleolysis agent.

© 2015 Lippincott Williams & Wilkins, Inc.