ADAMTS Proteases in Cartilage Degradation and Osteoarthritis

ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) proteases constitute a family of secreted zinc-dependent enzymes that orchestrate the remodelling of the cartilage extracellular matrix. In healthy cartilage, a balanced activity of these enzymes supports normal turnover of proteoglycans, collagens and other matrix components. In osteoarthritis, however, key family members—particularly ADAMTS-4 and ADAMTS-5—become dysregulated, leading to excessive cleavage of aggrecan, the major cartilage proteoglycan. This initiates a cascade of cartilage erosion, chondrocyte hypertrophy and subchondral bone remodelling that drives joint pain and functional decline. Recent advances have elucidated molecular controls over ADAMTS gene expression, their activation by inflammatory mediators and mechanical stress, and their interplay with chondrocyte signalling pathways. Therapeutic efforts now focus on sensitive detection of protease activity, selective inhibition of aggrecanase function, and modulation of upstream regulatory networks. Together, these lines of inquiry aim to restore matrix homeostasis, slow disease progression and open new avenues for precision medicine in joint disorders.

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ADAMTS Proteases in Cartilage Degradation and Osteoarthritis publication trend

The graph below shows the total number of articles in adamts proteases in cartilage degradation and osteoarthritis across all publications each year (not limited to Nature Index journals).

Technical terms

ADAMTS protease: A secreted zinc-dependent enzyme with thrombospondin motifs that cleaves extracellular matrix components.

Aggrecan: A large cartilage proteoglycan that provides compressive resistance and interacts with collagen fibrils.

Extracellular matrix: The network of proteoglycans, collagens and glycoproteins that gives cartilage its structure and mechanical properties.

Chondrocyte: The specialised cartilage cell responsible for matrix synthesis, maintenance and response to mechanical and inflammatory stimuli.

Aggrecanase: An enzyme, primarily ADAMTS-4 or ADAMTS-5, that cleaves the core protein of aggrecan, leading to cartilage degradation.

Epigenetic modification: A heritable change in gene expression caused by chemical alterations (such as N6-methyladenosine) of DNA or RNA rather than changes in the genetic code.

FRET substrate: A peptide probe labelled with donor and acceptor fluorophores that reports protease activity by energy transfer changes upon cleavage.

References

1. Development of Selective ADAMTS‑5 Peptide Substrates to Monitor Proteinase Activity. Journal of Medicinal Chemistry (2023).
2. Epigenetic regulatory mechanism of ADAMTS12 expression in osteoarthritis. Molecular Medicine (2023).
3. ADAMTS5 in Osteoarthritis: Biological Functions, Regulatory Network, and Potential Targeting Therapies. Frontiers in Molecular Biosciences (2021).
4. The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) family. Genome Biology (2015).