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ADAMTS-9 in Mouse Cartilage Has Aggrecanase Activity That Is Distinct from ADAMTS-4 and ADAMTS-5.


ABSTRACT: A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4 and ADAMTS-5 are the principal aggrecanases in mice and humans; however, mice lacking the catalytic domain of both enzymes (TS-4/5?cat) have no skeletal phenotype, suggesting there is an alternative aggrecanase for modulating normal growth and development in these mice. We previously identified aggrecanase activity that (a) cleaved at E?G rather than E?A bonds in the aggrecan core protein, and (b) was upregulated by retinoic acid but not IL-1?. The present study aimed to identify the alternative aggrecanase. Femoral head cartilage explants from TS-4/5?cat mice were stimulated with IL-1? or retinoic acid and total RNA was analysed by microarray. In addition to ADAMTS-5 and matrix metalloproteinase (MMP)-13, which are not candidates for the novel aggrecanase, the microarray analyses identified MMP-11, calpain-5 and ADAMTS-9 as candidate aggrecanases upregulated by retinoic acid. When calpain-5 and MMP-11 failed to meet subsequent criteria, ADAMTS-9 emerged as the most likely candidate for the novel aggrecanase. Immunohistochemistry revealed ADAMTS-9 expression throughout the mouse growth plate and strong expression, particularly in the proliferative zone of the TS-4/5-?cat mice. In conclusion, ADAMTS-9 has a novel specificity for aggrecan, cleaving primarily at E?G rather than E?A bonds in mouse cartilage. ADAMTS-9 might have more important roles in normal skeletal development compared with ADAMTS-4 and ADAMTS-5, which have key roles in joint pathology.

SUBMITTER: Rogerson FM 

PROVIDER: S-EPMC6387038 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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ADAMTS-9 in Mouse Cartilage Has Aggrecanase Activity That Is Distinct from ADAMTS-4 and ADAMTS-5.

Rogerson Fraser M FM   Last Karena K   Golub Suzanne B SB   Gauci Stephanie J SJ   Stanton Heather H   Bell Katrina M KM   Fosang Amanda J AJ  

International journal of molecular sciences 20190129 3


A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4 and ADAMTS-5 are the principal aggrecanases in mice and humans; however, mice lacking the catalytic domain of both enzymes (TS-4/5∆cat) have no skeletal phenotype, suggesting there is an alternative aggrecanase for modulating normal growth and development in these mice. We previously identified aggrecanase activity that (a) cleaved at E↓G rather than E↓A bonds in the aggrecan core protein, and (b) was upregulated by retino  ...[more]

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