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Gene Review:

Adamts4 - ADAM metallopeptidase with thrombospondin...

Rattus norvegicus

Synonyms: A disintegrin and metalloproteinase with thrombospondin motifs 4, ADAM-TS 4, ADAM-TS4, ADAMTS-4, Aggrecanase-1

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Disease relevance of Adamts4

Aggrecanase inhibitors may provide a unique means to halt the progression of cartilage destruction in osteoarthritis [1].

High impact information on Adamts4

ADAMTS4 (a disintegrin and metalloproteinase with thrombospondin motifs), a protease that selectively cleaves lecticans, was detected in cultures of neurons, astrocytes and microglia [2].
In rats that seized after kainate, there was a dramatic elevation in ADAMTS1 and ADAMTS4 transcript that correlated and co-localized with a robust elevation in an extractable, 55-kDa fragment of brevican in temporal lobe and hippocampus [3].
In untreated rats, in situ hybridization and reverse transcriptase polymerase chain reaction indicated that ADAMTS4 expression was higher than ADAMTS1 and was localized to hippocampus, temporal lobe and other areas of cortex, striatum and hypothalamus [3].
ADAMTS4 mRNA expression in these regions correlated with the presence of the QEAVESE neo-epitope, which was concentrated in perineuronal nets and in neuropil [3].
ADAMTS-4 mRNA and protein were up-regulated by TNF in primary human astrocyte cultures [4].

Biological context of Adamts4

RESULTS: Immobilization and dynamic compression affect anabolic and catabolic genes, with an overall downregulation of types 1 and 2 collagen and upregulation of aggrecanase, collagenase, and stromelysin in the anulus [5].

Anatomical context of Adamts4

ADAMTS1, ADAMTS4, ADAMTS5 and versican were expressed in dental pulp cells, odontoblasts, cementoblasts, cementocytes, periodontal ligament cells, osteoblasts and osteocytes [6].
The present study suggests that dental pulp cells, odontoblasts, cementoblasts, cementocytes, periodontal ligament cells, osteoblasts and osteocytes may be involved in both production and degradation of versican with secreting ADAMTS1, ADAMTS4 and ADAMTS5 [6].

Other interactions of Adamts4

One subtracted gene that showed the Abeta-induced expression was rat ADAMTS-4 (a disintegrin and metalloproteinase with thrombospondin motifs) [7].
3-Hydroxy-4-arylsulfonyltetrahydropyranyl-3-hydroxamic acids are novel inhibitors of MMP-13 and aggrecanase [8].

Analytical, diagnostic and therapeutic context of Adamts4

The mRNA expression of ADAMTS1, ADAMTS4, ADAMTS5 and versican was localized using in situ hybridization [6].

References

Synthesis and biological evaluation of biphenylsulfonamide carboxylate aggrecanase-1 inhibitors. Xiang, J.S., Hu, Y., Rush, T.S., Thomason, J.R., Ipek, M., Sum, P.E., Abrous, L., Sabatini, J.J., Georgiadis, K., Reifenberg, E., Majumdar, M., Morris, E.A., Tam, S. Bioorg. Med. Chem. Lett. (2006) [Pubmed]
Altered production and proteolytic processing of brevican by transforming growth factor beta in cultured astrocytes. Hamel, M.G., Mayer, J., Gottschall, P.E. J. Neurochem. (2005) [Pubmed]
Association between protease-specific proteolytic cleavage of brevican and synaptic loss in the dentate gyrus of kainate-treated rats. Yuan, W., Matthews, R.T., Sandy, J.D., Gottschall, P.E. Neuroscience (2002) [Pubmed]
ADAMTS-1 and -4 are up-regulated following transient middle cerebral artery occlusion in the rat and their expression is modulated by TNF in cultured astrocytes. Cross, A.K., Haddock, G., Stock, C.J., Allan, S., Surr, J., Bunning, R.A., Buttle, D.J., Woodroofe, M.N. Brain Res. (2006) [Pubmed]
Effects of immobilization and dynamic compression on intervertebral disc cell gene expression in vivo. MacLean, J.J., Lee, C.R., Grad, S., Ito, K., Alini, M., Iatridis, J.C. Spine. (2003) [Pubmed]
Expression of Versican and ADAMTS During Rat Tooth Eruption. Sone, S., Nakamura, M., Maruya, Y., Takahashi, I., Mizoguchi, I., Mayanagi, H., Sasano, Y. Journal of molecular histology. (2005) [Pubmed]
ADAMTS-4 (a disintegrin and metalloproteinase with thrombospondin motifs) is transcriptionally induced in beta-amyloid treated rat astrocytes. Satoh, K., Suzuki, N., Yokota, H. Neurosci. Lett. (2000) [Pubmed]
3-Hydroxy-4-arylsulfonyltetrahydropyranyl-3-hydroxamic acids are novel inhibitors of MMP-13 and aggrecanase. Noe, M.C., Snow, S.L., Wolf-Gouveia, L.A., Mitchell, P.G., Lopresti-Morrow, L., Reeves, L.M., Yocum, S.A., Liras, J.L., Vaughn, M. Bioorg. Med. Chem. Lett. (2004) [Pubmed]

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