The Connection Between Aggrecan, Chondrogenesis, And Height

Protein_ACAN_PDB_1tdqA compound or protein that I have been reading a lot about in the literature is aggrecan and it seems that have some direct influence and effect on chondrogenesis and the overall height. This is my attempt to do some basic research on Aggrecan.

I start off by just reading the Wikipedia article on aggrecan to get a general idea on what it is and what it does. The first few sentences makes me realize that aggrecan may be a not more important than I had previously believed.

“Aggrecan also known as cartilage-specific proteoglycan core protein (CSPCP) or chondroitin sulfate proteoglycan 1 is a protein that in humans is encoded by the ACAN gene. This gene is a member of the aggrecan/versican proteoglycan family. The encoded protein is an integral part of the extracellular matrix in cartilagenous tissue and it withstands compression in cartilage…Aggrecan is a proteoglycan, or a protein modified with large carbohydrates”

We remember that in at least the hyaline type cartilage found in the epiphyseal growth plates, the chondrocytes did excrete two main types of waste which would go on to make the extracellular matrix of the cartilage, type II collagen and proteoglycans. I had only briefly touched on looking at proteoglycans in the past in a very early post “The Effect On Height By Proteoglycans“. Looking back on these older posts I realize that I had no idea what I was doing or researching and understood very little of the details and mechanics of the cartilage that form the growth plates. I was trying and that is what I think is important.

From the name itself of aggrecan “cartilage specific proteoglycan core protein” it suggest that this type of protein is a type of proteoglycan which is either mainly or only found in cartilage. The fact that another name for it is chondroitin sulfate proteoglycan 1 shows that it may be similar to to the glycoaminoglycans we saw in the past or the non-sulfated type like the hyaluranon (aka hyaluronic acid)

From Wikipedia…

Aggrecan is a high molecular weight (1×106 < M < 3×106) proteoglycan. It exhibits a bottlebrush structure, in which chondroitin sulfate and keratan sulfate chains are attached to an extended protein core.

Aggrecan has a molecular mass >2,500 kDa. The core protein (210–250 kDa) has 100–150 glycosaminoglycan (GAG) chains attached to it. Along with type-II collagen, aggrecan forms a major structural component of cartilage, particularly articular cartilage.

What we are seeing is that aggrecans make up a huge major component in the matrix of most cartilage. When originally we were looking at the composition of cartilage, we only called them by the names, Collagen Type 2 and Proteoglycans. Now we can be more specific in seeing that one major type of proteoglycan found in at least articular cartilage is the aggrecan. The aggrecan itself seems to be much bigger than any glycoaminoglycan we saw before. There is a core protein part, and from the core protein projects about a couple hundred GAG chains, many of them being chondroitin sulfate and keratan sulfate.

If we remember from our past research on trying to find some type of supplement which can possible increase height, two major contenders were glucosamine sulfate and hyaluronic acid while another type, the chondroitin sulfate was very big as well. What we see from supplement stacks used from GrowTallForum.com was the use of glucosamine and chondroitin being used extensively. This suggest that GAGs have been the major source type of biological protein we were taking. At some point, after doing research on all three components, I tentatively decided that glucosamine sulfate and hyaluronic acid were two of three types of supplements which had the best chance of leading to some height increase for physically mature adults, even though those results might have been only a few milimeters of extra height at best.

It seems that overall, the aggrecan has 4 major areas, with 2 areas being on the N end and one area in the C end. There are areas in the compound called G1, G2, and G3 which have the function of chondrocyte apoptosis, hyaluronan binding, aggregation, and cell binding.

From the section for functions….

Aggrecan plays an important role in mediating chondrocyte-chondrocyte and chondrocyte-matrix interactions through its ability to bind hyaluronan

I am not sure about this but I would be willing to make a guess at this point that when the wikipedia article is referring to chondrocyte-chondrocyte interactions, the issue of orientation and chondrocyte arrangement might be included. One of the domains called G1 seems to bind to hyaluranon and proteins and form big complexes of protein that is 3-parts. This might involve a hyaluranon-aggrecan-protein system.

This next part in the wikipedia article was extremely englightening…

Aggrecan provides intervertebral disc and cartilage with the ability to resist compressive loads. The localized high concentrations of aggrecan provide the osmotic properties necessary for normal tissue function with the GAGs producing the swelling pressure that counters compressive loads on the tissue. This functional ability is dependent on a high GAG/aggrecan concentration being present in the tissue extracellular matrix.

This shows that there is a clear direct link between having extra aggrecan & GAGs and resisting the loss of height from intervertebral disk compression from gravitational loading. This is not only the first indication that taking certain GAGs may indeed lead to certain height increase like chondroitin sulfate and hyaluronic acid, but that any process to increase aggrecan especially in the cartilage that are part of a joint can lead to some height increase.

At the end of the clinical significance section it says…

Osteoarthritis is characterized by the slow progressive deterioration of articular cartilage. Cartilage contains up to 10% proteoglycan consisting of mainly the large aggregating chondroitin sulfate proteoglycan aggrecan.

It seems to validate the idea that the majority of proteoglycan types found in cartilage is the aggrecan. Since chondroitin sulfate does form a huge part of the chains that make the globular parts of the aggrecan, maybe taking chondroitin sulfate and keratan sulfate can really do lead to at least some decreased height loss from intervertebral decompression throughout a day.

Conclusion:

From only a quick analysis of just the Wikipedia article on aggrecan, I am willing to guess that this large complex of a protein is critical in giving the structure and strength of cartilage in general. I would say that aggrecan can lead to some height increase if one can get enough of hyaluranon and aggrecan in the right cartilage regions in one’s body. I am quite confident in showing that getting enough GAGs and aggrecan into one’s system can possibly lead to lead height loss throughout the day and may also help prevent the onset of osteoarthritis.