A review of ADAMTS5, the main aggrecan-cutting enzyme in cartilage
This 2021 review describes ADAMTS5 as the major aggrecanase degrading joint cartilage matrix. It covers what overactivates it, including senescence, inheritance, inflammation and mechanical stress, the signalling pathways that control it, and the antibodies, small molecules and RNA therapies developed against it in the lab and in animals.
What they did
This is a review of published research, not a new experiment. The authors summarised how ADAMTS5 is regulated, its role in joint inflammation, in how cartilage cells respond to mechanical load and in chondrocyte hypertrophy, and the newer strategies for blocking it.
What they found
The review describes ADAMTS5 as the major aggrecanase degrading articular cartilage matrix. Senescence, inheritance, inflammation and mechanical stress contribute to its overactivation. Signalling pathways that control it include Runx2, Fgf2, Notch, Wnt, NF-kB and YAP/TAZ. Monoclonal antibodies and small molecule inhibitors against ADAMTS5 proved beneficial in cells and in animals, and newer RNA therapies showed potential in animal models.
What it can't tell us
A review adds no new data, and its picture depends on the studies chosen. The abstract reports benefits in cells and animals only, so it does not show any ADAMTS5 blocker working in people. It does not compare ADAMTS5 with MMP13.
Why it matters
MMP13 and ADAMTS5 are the two enzymes most often named in cartilage breakdown. ADAMTS5 goes after aggrecan, MMP13 after type II collagen. Some of the same signals, NF-kB and Runx2 among them, control both, which is why studies such as Jain 2024 and Rong 2019 measured them together.
The paper
- Jiang L, Lin J, Zhao S et al. ADAMTS5 in Osteoarthritis: Biological Functions, Regulatory Network, and Potential Targeting Therapies. Front Mol Biosci 2021.
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