ADAMTS4

ADAMTS4

ADAMTS4 (A Disintegrin and Metalloproteinase with Thrombospondin Motifs 4) is an enzyme that belongs to the ADAMTS family of proteins. These proteins are known for their roles in the degradation of extracellular matrix components, which is crucial in various physiological and pathological processes.

Structure

ADAMTS4 is a member of the ADAMTS family, characterized by a multi-domain structure that includes a propeptide region, a metalloproteinase domain, a disintegrin-like domain, a thrombospondin type 1 motif, and a spacer region. The enzyme is synthesized as an inactive zymogen and requires proteolytic cleavage for activation.

Function

ADAMTS4 is primarily known for its ability to cleave aggrecan, a major component of cartilage. This activity is significant in the context of osteoarthritis, where excessive degradation of aggrecan by ADAMTS4 and related enzymes leads to cartilage breakdown and joint degeneration. ADAMTS4 is also involved in other processes such as tissue remodeling, inflammation, and angiogenesis.

Regulation

The activity of ADAMTS4 is regulated at multiple levels, including gene expression, zymogen activation, and inhibition by tissue inhibitors of metalloproteinases (TIMPs). Cytokines and growth factors can modulate the expression of ADAMTS4, influencing its role in disease processes.

Clinical Significance

Due to its role in cartilage degradation, ADAMTS4 is a target for therapeutic intervention in diseases like osteoarthritis. Inhibitors of ADAMTS4 are being explored as potential treatments to prevent or slow down the progression of cartilage damage.

Research

Ongoing research is focused on understanding the precise mechanisms by which ADAMTS4 contributes to disease and identifying specific inhibitors that can selectively block its activity without affecting other metalloproteinases.

Also see

• ADAMTS family
• Osteoarthritis
• Extracellular matrix
• Metalloproteinase