Inhibition of bovine nasal cartilage degradation by selective matrix metalloproteinase inhibitors

被引：38

作者：

Bottomley, KM ^{[1
]}

Borkakoti, N ^{[1
]}

Bradshaw, D ^{[1
]}

Brown, PA ^{[1
]}

Broadhurst, MJ ^{[1
]}

Budd, JM ^{[1
]}

Elliott, L ^{[1
]}

Eyers, P ^{[1
]}

Hallam, TJ ^{[1
]}

Handa, BK ^{[1
]}

Hill, CH ^{[1
]}

James, M ^{[1
]}

Lahm, HW ^{[1
]}

Lawton, G ^{[1
]}

Merritt, JE ^{[1
]}

Nixon, JS ^{[1
]}

Rothlisberger, U ^{[1
]}

Whittle, A ^{[1
]}

Johnson, WH ^{[1
]}

机构：

[1] F HOFFMAN LA ROCHE AG,CH-4070 BASEL,SWITZERLAND

来源：

BIOCHEMICAL JOURNAL | 1997年 / 323卷

关键词：

D O I：

10.1042/bj3230483

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 [生物化学与分子生物学]; 081704 [应用化学];

摘要：

N-terminal analysis of aggrecan fragments lost from bovine nasal cartilage cultured in the presence of recombinant human interleukin la revealed a predominant ARGSVIL sequence with an additional ADLEX sequence. Production of the ARGSVIL-containing fragments has been attributed to the action of a putative proteinase, aggrecanase. The minor sequence (ADLEX) corresponds to a new reported cleavage product; comparison of this sequence with the available partial sequence of bovine aggrecan indicates that this is the product of a cleavage occurring towards the C-terminus of the protein. Matrix metalloproteinase (MMP) inhibitors inhibited aggrecan loss from bovine nasal explants incubated in the presence of recombinant human interleukin la. A strong correlation between inhibition of aggrecan metabolism and inhibition of stromelysin 1 (MMP 3) (r = 0.93) suggests a role for stromelysin or a stromelysin-like enzyme in cartilage aggrecan metabolism. However, the compounds were approx. 1/1000 as potent in inhibiting aggrecan loss from the cartilage explants as they were in inhibiting stromelysin. There was little or no correlation between inhibition of aggrecan metabolism and inhibition of gelatinase B (MMP 9) or inhibition of collagenase 1 (MMP 1). Studies with collagenase inhibitors with a range of potencies showed a correlation between inhibition of collagenase activity and inhibition of collagen degradation in the cartilage explant assay. This indicates that in interleukin 1 alpha-driven bovine nasal cartilage destruction, stromelysin (or a closely related enzyme) is involved in aggrecan metabolism, whereas collagenase is principally responsible for collagen degradation.

引用

页码：483 / 488

页数：6

共 30 条

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