What is the Extracellular matrix (ECM)?

Ross Hauser, MD

There are many studies which suggest that patients heal better when they understand how they are healing. One of the most fascinating parts of our bodies’ healing components is the extracellular matrix (ECM). In this article we will discuss how comprehensive Prolotherapy repairs cartilage by impacting cartilage chondrocytes and their extracellular matrix.

The bricks and mortar of healing

What is the extracellular matrix? Chondrocytes are cells that are the building blocks of cartilage. Imagine the brick wall below is the cartilage in your knee. that has holes in it. Our body calls the chondrocytes to the area where the wall needs to be patched. The Chondrocytes are the bricks. The bricks are useless without mortar to hold them in place. So the chondrocytes secrete an extracellular matrix, their own mortar.

So imagine again:

  • A chemical process that tells the wall bricks are in the area available for repair
  • The wall sends signals to the bricks to attract them to where they need to line up for a good patch fit.
  • The brick arrives at the specific hole in the wall it was told to go to.
  • The brick fits itself into the hole and secures itself in place by secreting its own mortar
  • Now imagine this brick is joined by other bricks doing the same thing.  
  • Repaired brick wall

The simple illustration of this brick wall explains how regenerative medicine such as Prolotherapy, platelet rich plasma prolotherapy, and stem cell prolotherapy repairs damaged cartilage

When the mortar is too thin, the bricks don’t hold, osteoarthritis progresses

In reviewing the work of Italian researchers on the effectiveness of Platelet Rich Plasma in early stage knee osteoarthritis that appeared in the May 2017 edition of the medical journal Joint,1 we came across a great paragraph that describes how when the extracellular matrix is diluted by inflammation causing the cartilage bricks to fall out of the wall.

“Osteoarthritis is not related to only mechanical stress (wear and tear load), but many cellular and biochemical processes are also involved in its pathogenesis. In normal conditions, cartilage extracellular matrix is in a dynamic equilibrium. In particular, the balance between anabolic and catabolic activities of chondrocytes maintains the structural and functional integrity of cartilage. In osteoarthritis, a deregulated balance between proteinases degrading (protein enzymes in the inflammatory process breaks down) the extracellular matrix and their inhibitors (which should stop the process) may be responsible for cartilage degeneration.”

So what’s happening is that the extracellular matrix is being diluted and the things that protects it from this dilution are being attacked by protein enzymes in the inflammatory cycle that is out of control.

Stopping ECM dilution is one of the healing factors in PRP Prolotherapy

In the research we are discussing, the doctors tested whether a single injection of Platelet Rich Plasma (PRP) would be effective for patients in early stage knee osteoarthritis. The answer?

“a single dose of PRP in patients with knee osteoarthriti grade I or II is a safe an effective treatment for managing the symptoms associated with this pathology, especially pain, and achieving improvements in quality of life of patients.”1

How? Because one of the characteristics of PRP is that is works to change the chemical milieu of the joint environment. In the context of this article it sent the chemical signals necessary to strategically shut down this inflammation harmful to the extracellular matrix.

Stopping ECM degradation is one of the healing factors in stem cell prolotherapy

Please see this article to understand the role of stem cell therapy in cartilage repair and to see if you are a candidate 

  • When stem cells are injected into a diseased joint they start talking to the repair cells, the blood cells, the inflammatory cells, and the native stem cells in a “reboot” command to restart the natural healing of the joint. This comes under the phenomena of “cell signalling.”

However, the stem cells can be bogged down and the messages blurred by the oxidative stress caused by the chronic inflammation, so repair can take longer and be more challenging. This problem is what new research is trying to tackle. This new research is covered in our article How stem cells heal degenerative joint disease after years of cortisone and painkillers.

1 Martini LI, Via AG, Fossati C, Randelli F, Randelli P, Cucchi D, Barbour KE, Helmick CG, Theis KA, Al-Arfaj A, Al-Boukai AA. Single Platelet-Rich Plasma Injection for Early Stage of Osteoarthritis of the Knee. Joints. 2017 Mar;5(01):002-6.


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