By Emily Dickson
If you read the last blog post, you already know that biomarkers are indicators of something happening in the body.
When talking about cartilage, the biomarkers we are looking at have to do with the two main components of cartilage: type II collagen and proteoglycans.
In research, biomarkers are used to give us a hint about what’s going on in the animal. It’s a relatively easy, non-invasive way to get an accurate picture without having to pull cartilage out of a research animal’s joint.
While it’s not yet common practice for the everyday horse owner to have their horse's biomarkers tested (don’t call your vet asking them to pull joint fluid from your horse!), I do believe that as research expands and we understand more this might become a mainstream diagnostic test.
There’s a lot of potential for biomarkers to tell us in greater detail what is going on in the joint and the body, sometimes more so than an x-ray or ultrasound.
The study of biomarkers is fascinating to me because it helps us better understand the joint at the cellular level, and especially what happens during exercise or nutritional interventions. They can give us information sometimes before we can visually see the damage in a picture.
What is the CPII biomarker?
Carboxypropeptide of Type II Collagen (CPII) is a measure of type II collagen synthesis.
Chondrocytes, the master regulator of cells in cartilage, are the ones responsible for initiating collagen synthesis, but there are many steps in the collagen formation process. Collagen is produced in individual fibrils, or fibers, and each fibril goes through different stages of development, traveling from the chondrocyte to the extracellular matrix.
An important stage of development for the fibrils is an extensive cross-linking process. Think about the road system of a major city: roads are twisted and connected in a big intertwined grid or web.
As the collagen fibril goes through this process, there are pieces, or extensions, on the ends that are released as they are no longer needed. Think of them like baby teeth—you need them in your younger years until they are no longer necessary. Those released extensions are the basis of the CPII biomarker, and give us an idea of what is being synthesized in the joint.
CPII will end up in synovial fluid and blood, but is typically measured by analyzing a sample of synovial fluid. Synovial fluid, if you remember, is in direct contact with cartilage, so it contains the most accurate picture of what is going on in a particular joint, as opposed to blood, which travels all over the body, and therefore, contains levels of things that may be unrelated to the joint.
What does CPII tell us about the equine joint?
You might initially think that higher CPII levels are a good thing (more cartilage is ideal, right?!), but it can actually indicate damage. This is where there is some ambiguity with biomarkers.
Think about exercise. Obviously, it’s a good thing. We know this. Exercise is necessary for normal joint function, regeneration, and stimulating blood flow, not to mention all the other health-related benefits.
On the other hand, we also know that exercise done wrong can cause excessive damage to joints due to the creation of “micro tears” in cartilage. Some stress is good. But when there is too much damage too fast, the body cannot repair itself quickly enough and things start to go haywire.
Namely, too much stress causes increased inflammation. I know inflammation is a buzzword these days, but there’s a reason: it’s a really big problem. Inflammation doesn’t just do one thing, it causes a whole cascade of downstream effects that can be highly destructive to the joint and the entire body.
Studies have shown that CPII is elevated in young, growing horses, horses undergoing exercise, and in diseased joints, such as osteoarthritis.
While this is a good thing, as it indicates that the joint is attempting to repair itself in the face of insult, it is important to realize that too much synthesis could also be a red flag.
While we do want collagen synthesis, what we really want is a balance of synthesis and degradation. Enter C2C, the next biomarker in the series.