NEUTRAL PROTEINASES IN HUMAN INTERVERTEBRAL DISC - ROLE IN DEGENERATION AND PROBABLE ORIGIN

被引:60
作者
FUJITA, K
NAKAGAWA, T
HIRABAYASHI, K
NAGAI, Y
机构
[1] Department of Orthopaedic Surgery, Urawa City Hospital, Urawa, Saitama
[2] Department of Orthopaedic Surgery, Keio University, School of Medicine, Tokyo, Shinjuku
[3] Department of Tissue Physiology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo
关键词
INTERVERTEBRAL DISC; NEUTRAL PROTEINASE; LEUKOCYTE ELASTASE;
D O I
10.1097/00007632-199310000-00009
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Neutral proteinases were partially purified from human intervertebral disc by extraction with guanidine hydrochloride followed by Sephadex G-75 column chromatography. They showed gelatinolytic and elastolytic activities at neutral pH. The apparent molecular weights of these enzymes were 70 KD and 25 KD, the former being the complexed form of the latter. The sensitivity to various synthetic inhibitors indicated these enzymes to be serine elastases. Furthermore, they were considered to be leukocyte elastases because anti-leukocyte elastase antibody inhibited the proteinase activity of these enzymes. Proteinase activity was not detected in normal discs, except for some slight activity in the end-plate, In contrast, the degenerated discs showed high activity, especially in the nucleus pulposus and end-plate. Similar high levels of proteinase activity were found in the vertebral body adjacent to normal as well as degenerated discs. These findings suggest that leukocyte elastase, which is normally present in the vertebral body, flows into and degrades the matrix of the intervertebral disc under pathologic conditions.
引用
收藏
页码:1766 / 1773
页数:8
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共 41 条
  • [1] Adams P., Muri H., Qualitative changes with age of proteoglycans of human lumbar discs, Ann Rheum Dis, 35, pp. 289-296, (1976)
  • [2] Adams P., Eyre D.R., Muir H., Biochemical aspects of development and aging of human lumbar intervertebral discs, Rheumatol Rehabil, 16, pp. 22-29, (1977)
  • [3] Barrett A.J., Proteases M.J., A Glossary and Bibliography. Vol. 1. Endopeptidase, pp. 32-180, (1980)
  • [4] Bunning R., Crawford A., Richardson H.J., Et al., Interleukin 1 preferentially stimulates the production of tissue-type plasminogen activator by human articular chondrocytes, Biochim Biophys Acta, 924, pp. 473-482, (1987)
  • [5] Castillo M.J., Nakajima K., Zimmerman M., Et al., Sensitive substrates for human leukocyte and porcine pancreatic elastase: A study of the merits of various chromophoric and fluorogenic leaving groups in assay for serine proteases, Anal Biochem, 99, pp. 53-64, (1979)
  • [6] Dingle T., Horsfield P., Honor Fell B., Et al., Breakdown of proteoglycan and collagen induced in pig articular cartilage in organ culture, Ann Rheum Dis, 34, pp. 303-311, (1975)
  • [7] Eyre D.R., Muir H., Interchanging radical distribution in annulus fibrosus, Biochem J, 157, pp. 267-270, (1976)
  • [8] Eyre D.R., Muir H., Quantitative analysis of type I and II collagens in human intervertebral discs at various ages, Biochim Biophys Acta, 492, pp. 29-42, (1977)
  • [9] Golds E.E., Ciosek C.P., Hamilton J.A., Differen tial release of plasminogen activator and latent collagenase from mononuclear cell-stimulated synovial cells, Arthritis Rheum, 26, pp. 15-21, (1983)
  • [10] Heussen C., Dowdle E.B., Electrophoretic analysis of plasminogen activators in polyacrylamide gels containing sodium dodecyl sulfate and copolymerized substrates, Anal Biochem, 102, pp. 196-202, (1980)