Genetic variation including nonsynonymous polymorphisms of a major aggrecanase, ADAMTS-5
, in susceptibility to osteoarthritis.
The breakdown of AGC is believed to be initiated by a disintegrin and metalloproteinase with thrombospondin-like motifs (ADAMTS)-4 and ADAMTS-5
Brevican is also degraded by various MMPs and ADAMTS proteases [56, 57], including ADAMTS-4  and ADAMTS-5
Small Molecules to Inhibit ADAMTS-5
for Osteoarthritis 31
Shi, "Expression of ADAMTs-5
and TIMP-3 in the condylar cartilage of rats induced by experimentally created osteoarthritis," Archives of Oral Biology, vol.
In the EGCG-treated (intraperitoneal injection) mice, articular cartilage shows downregulation of MMP-1, MMP-3, MMP-8, MMP-13, ADAMTS-5
, IL-1[beta], and TNF[alpha] mRNA and upregulation of CBP/p300 interacting transactivator with ED-rich tail 2 (CITED2), which suppresses MMPs transcription .
The expression levels of MMP-1, MMP-3, MMP13, ADAMTS-4, ADAMTS-5
, collagen type II alpha 1 chain (COL2A1), cartilage oligomeric matrix protein (COMP), collagen type I alpha 2 chain (COL1A2), and collagen type X alpha 1 chain (COL10A1) mRNA in the articular cartilage were determined by RT-PCR assays using a SYBR green kit (Sigma-Aldrich) according to the method described by Takahito  and Hyuck .
After 24 hrs of stimulation with DAMPs, culture media were dialyzed and concentrated for examination of MMP-1, MMP-3, MMP-13, ADAMTS-5
, and ADAM-8.
The primary antibodies included rabbit polyclonal antibodies specific for ADAMTS-1 (1:50; Abcam, Cambridge, United Kingdom), ADAMTS-4 (1:50; AVIVA Systems Biology, San Diego, California), ADAMTS-5
(1:100; Novus, Littleton, Colorado), ADAMTS-14 (1:100, Abcam), and rabbit polyclonal IgG purified from preimmune serum samples (1:50 or 1:100, ab27478; Abcam).
During the OA process, aggrecans are cleaved at specific Glu-Xaa peptide bonds by aggrecanases such as ADAMTS-4 and ADAMTS-5
, resulting in a breakdown of HA and link proteins and a decrease in stable ternary complexes in the extracellular matrix .
Results: We report that low mass 4.5-kDa HA-fs enhance MMPs, including MMP -3 and 13 but not an ADAMTS-5
in chondrocytes and cartilage explant cultures, to a lesser extent than a Fn-f, included as a positive control, but enhance cartilage matrix damage to a similar extent as Fn-f.
It is also suggested that another enzyme, aggrecanase-2, or ADAMTS-5
(a disintegrin and MMP domain with thrombospondin motifs), plays a predominant role in the proteolysis of OA cartilage aggrecan.