Recently the commenter who goes by the name Matheus from Brazil gave me a lot of studies which showed the effects on longitudinal bone growth by a multiple of chemical compounds. His research has been very extensive and broad and it took me many hours to figure out what exactly he was saying and to condense all that information into a format that the average reader can take and understand.

I had talked about his research in Podcast Episode #11. Click on “Natural Height Growth Podcast, Episode 11: I Review And Outline All The Research And Studies Matheus Has Shown To Me” to listen

Some of the compounds he talked about I am aware of since some of his references are to posts I had written months ago. However there was a few compounds which I have never heard about and seem to be rather important in either epiphyseal growth plate cartilage physiology or in the endochondral ossification process.

The first compound I wanted to do more research on is something called Matrix Gla Protein.

From the podcast post I had listed this about Matrix Gla Protein

MGP (Matrix Gla Protein-derived K2) which is produced by Vitamin K2 – inhibits the calcification of tissues and cartilages – is the major inhibitor of human body tissue calcification and seems to have much influence on chondrocytes. (Coordinated expression of matrix Gla protein is required during endochondral ossification for chondrocyte survival)

The study: Coordinated expression of Matrix Gla protein is required during endochondral ossification for chondrocyte survival

Summary of the study:

So first a little background on this compound. It weighs on average around 14 kiloDaltons, which is considered average size for proteins and peptides. It is part of of the family known as Gla which has the function of binding to minerals. There is two primary functions that is listed, both in terms of decalcification of specific types of tissue. So the Matrix Gla Protein inhibits…

1. extracellular matrix calcification in arteries
2. extracellular matrix calcification in the epiphyseal growth plate

MGP binds calcium ions and hydroxyapatite via its five γ-carboxylated glutamic acid (Gla) residues

Other things that show how the MGP regulates or functions within growth plate is noted below from the study…

“…the epiphyseal growth plate is disorganized in the MGP-deficient mouse, in that the proliferative chondrocytes fail to form regular palisaded columns and hypertrophic chondrocytes are absent. In this situation, it is unclear whether the aberrant calcification causes disruption of the normal proliferative chondrocyte zone architecture, or if MGP has a direct influence on chondrocyte maturation. However, misexpression of MGP in chick embryo limb buds has been shown to inhibit the formation of hypertrophic chondrocytes during endochondral bone growth…”

The location where this compound is expressed seem to be in two regions that are not next to each other, at the proliferative and late hypertrophic chondrocyte zones. In vitro studies showed the same pattern of biphasic expression pattern as in vivo. There is supposed to be a type of compound known as MGP anti-serum which seem to have the reverse effects as the MGP. When the anti-serum is used for the proliferative chondrocytes that are expressing the MGP in that zone, the chondrocytes started to die much early that they were supposed to be.

From the study, we learn that the Matrix Gla Protein has 4 main types of effects when either overexpressed or underexpressed in specific regions. They are…

1. overexpression of MGP in maturing chondrocytes induces apoptosis
2. underexpression of MGP in proliferative and hypertrophic chondrocytes induced apoptosis
3. overexpression of MGP during the hypertrophic phase has no effect on chondrocyte viability
4. overexpression of MGP during the hypertrophic phase does reduce mineralization.

If we combine all the effects of changing the expression level of MGP together we realize that increase of MGP expression is a good thing for epiphyseal cartilage health, in not becoming mineralized too fast. However it might be important to also control the expression level of mature chondrocytes so that they can go through the necessary steps for apoptosis in the ossification layer.