Surreal image of a spine transforming into a crystalline ECM network.

Unlocking the Mystery of Axial Spondyloarthritis: Are Matrix Metalloproteinases the Key?

Reese Marlowe in Health & Wellness December 2025 • 4 min read.

"New research explores the link between matrix degradation and radiographic progression in axial spondyloarthritis, offering hope for early detection and treatment."

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease primarily affecting the spine and sacroiliac joints. This condition, characterized by inflammation, can lead to significant pain, stiffness, and, over time, structural damage visible on X-rays, a stage known as radiographic axial spondyloarthritis (r-axSpA).

A hallmark of axSpA is the remodeling of the extracellular matrix (ECM), the structural network surrounding cells in tissues like bone and cartilage. This remodeling process involves the breakdown and rebuilding of the ECM, but in axSpA, this process becomes dysregulated. Scientists are keen on understanding how ECM remodeling contributes to the progression of axSpA and whether it can be targeted to prevent or slow down the disease.

One area of intense research focuses on matrix metalloproteinases (MMPs), a family of enzymes that play a crucial role in ECM degradation. Researchers are investigating whether specific MMPs or their byproducts can serve as biomarkers, measurable indicators, of disease activity and progression in axSpA. The ability to identify individuals at high risk of radiographic progression early in the disease course could revolutionize patient care, allowing for timely interventions and personalized treatment strategies.

Decoding MMPs: What Role Do They Play in Axial Spondyloarthritis?

Surreal image of a spine transforming into a crystalline ECM network.

Recent research published in 'RMD Open' delved into the potential link between MMP-driven ECM degradation and radiographic progression in individuals with r-axSpA. The study aimed to determine whether biomarkers of ECM remodeling, specifically those related to MMP activity, could predict the advancement of structural damage in the spine over a two-year period.

The study included 122 patients diagnosed with r-axSpA from the Outcome in Ankylosing Spondylitis International Study (OASIS). These patients had comprehensive clinical data, serum samples, and spinal radiographs assessed at baseline and two years later. Researchers measured several biomarkers related to the degradation of different ECM components, including:

C1M: A fragment resulting from MMP-mediated degradation of type I collagen.
C5M: A fragment resulting from MMP-mediated degradation of type V collagen.
C6M: A fragment resulting from MMP-mediated degradation of type VI collagen.
VICM: A citrullinated and MMP-degraded fragment of vimentin.

The researchers then analyzed the relationship between these biomarkers at baseline and the change in spinal radiographic scores (mSASSS) over the two-year follow-up, adjusting for potential confounding factors such as age, gender, and disease duration. Surprisingly, the study found limited evidence to support a strong association between the measured MMP-related biomarkers and radiographic progression in r-axSpA.

What's Next for Axial Spondyloarthritis Research?

While this particular study didn't establish a clear link between the selected MMP biomarkers and radiographic progression, it doesn't diminish the importance of ECM remodeling in axSpA. Future research may explore other MMPs, different ECM components, or more sophisticated imaging techniques to capture subtle changes in spinal structures. Additionally, investigating the role of these biomarkers in earlier stages of axSpA, before radiographic damage is evident, could provide valuable insights into disease pathogenesis and potential therapeutic targets.

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This article is based on research published under:

DOI-LINK: 10.1136/rmdopen-2018-000648, Alternate LINK

Title: Is Radiographic Progression In Radiographic Axial Spondyloarthritis Related To Matrix Metalloproteinase Degradation Of Extracellular Matrix?

Subject: Immunology

Journal: RMD Open

Publisher: BMJ

Authors: Anne Sofie Siebuhr, Desirée Van Der Heijde, Anne-C Bay-Jensen, Morten Asser Karsdal, Robert Landewé, Astrid Van Tubergen, Sofia Ramiro

Published: 2018-05-01

Everything You Need To Know

What is axial spondyloarthritis (axSpA), and how does it affect the body?

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease that primarily affects the spine and sacroiliac joints. The inflammation associated with axSpA can cause significant pain and stiffness. Over time, this inflammation can lead to structural damage that becomes visible on X-rays, which is then classified as radiographic axial spondyloarthritis (r-axSpA). The remodeling of the extracellular matrix (ECM), a structural network surrounding cells, is also a key characteristic, involving the breakdown and rebuilding of tissues like bone and cartilage. When this process becomes dysregulated, it contributes to the progression of axSpA.

What are matrix metalloproteinases (MMPs), and why are they important in the context of axial spondyloarthritis (axSpA)?

Matrix metalloproteinases (MMPs) are a family of enzymes that play a crucial role in the degradation of the extracellular matrix (ECM). In the context of axial spondyloarthritis (axSpA), researchers are investigating whether specific MMPs or their byproducts can serve as biomarkers. These biomarkers could indicate disease activity and progression. Identifying individuals at high risk of radiographic progression early on could revolutionize patient care by allowing for timely interventions and personalized treatment strategies. The study mentioned focuses on MMP-related biomarkers like C1M, C5M, C6M, and VICM to predict structural damage progression in r-axSpA.

What did the 'RMD Open' study reveal about the link between MMP-driven ECM degradation and radiographic progression in r-axSpA?

The 'RMD Open' study investigated the link between matrix metalloproteinases (MMP)-driven extracellular matrix (ECM) degradation and radiographic progression in individuals with radiographic axial spondyloarthritis (r-axSpA). The study measured biomarkers like C1M, C5M, C6M, and VICM, which are related to the degradation of different ECM components, to see if they could predict the advancement of structural damage in the spine over two years. Surprisingly, the study found limited evidence to support a strong association between these specific MMP-related biomarkers and radiographic progression in r-axSpA.

If the study found limited evidence linking specific MMP biomarkers to radiographic progression in r-axSpA, what other research avenues are being considered?

Even though the study didn't establish a clear link between the selected matrix metalloproteinases (MMP) biomarkers and radiographic progression, the importance of extracellular matrix (ECM) remodeling in axial spondyloarthritis (axSpA) remains significant. Future research may explore other MMPs, different ECM components, or more advanced imaging techniques to better capture subtle changes in spinal structures. Additionally, investigating the role of these biomarkers in earlier stages of axSpA, before radiographic damage is evident, could provide valuable insights into the disease's pathogenesis and potential therapeutic targets.

What are the potential implications of identifying biomarkers like C1M, C5M, C6M and VICM in the early stages of axial spondyloarthritis (axSpA)?

Identifying biomarkers such as C1M, C5M, C6M, and VICM in the early stages of axial spondyloarthritis (axSpA) could revolutionize patient care. These biomarkers, related to matrix metalloproteinases (MMPs) and extracellular matrix (ECM) degradation, could help identify individuals at high risk of radiographic progression before structural damage becomes extensive. This early detection would enable timely interventions, personalized treatment strategies, and potentially slow down or prevent the progression of the disease, significantly improving the quality of life for those affected. Further research is needed to explore their roles in pre-radiographic stages.