Something that I had discovered while I was doing research on the retinoic acid in the post “Endogenous Retinoic Acid Negatively Regulates Growth Plate Chondrogenesis And Longitudinal Growth” were two compounds which really got me excited in the research.
It seems that while retinoic acid inhibits longitudinal growth of the long bones, it’s antagonist known as the Retinoic Acid Receptor antagonist (aka RAC antagonist) seems to be able to actually reverse the inhibitory effects of RA. it seems to be able to make the mineralization, calcification, and chondrocyte maturation process go in reverse and turn cartilage extracellular matrix which have started to mineralize and accumulate with calcium deposits known as hydroxyapatite back to the collagenous and glycoaminoglycan filled tissue it was originally.
What makes the RAC antagonist so promising was the fact that the RA was fed to the lab rat of a single dosage orally and the effects on the growth plates and endochondral ossification became obvious after just a few days. If the RA can be taken orally, then it might be possible for the RAR antagonist to be taken orally as well.
If the RAR antagonist can indeed be taken orally, then what we have would be one of the first and only true scientifically validated compounds discovered which can actually accelerate growth in growing children. This would have huge implications for children around the world who developed stunted growth from bad nutrition. If the RAR antagonist can be separated and isolated, using chemistry devices like HPLCs, and then concentrated, we might be able to mass produce this compound element.
What is interesting is that the RAR antagonist can reverse the calcification and mineralization process so even if a person had a sliver of open growth plates left, they can start growing maybe even in a few weeks of a few millimeters.
Since the human body produces the retinoic acid and the retinoic acid receptor antagonist endogenously, it would be safe to intake orally/ ingest. It is safe for human oral consumption.
The 2nd compound which I discovered which may have evern bigger implications as I had researched in the previous post linked above is Parathyroid Hormone, PTH.
In that post, I had quoted a phrase from the study entitled “Retinoic acid induces rapid mineralization and expression of mineralization-related genes in chondrocytes.“
“Mineralization was completely abolished by treatment with parathyroid hormone; this profound effect…”
It seems that the PTH has the ability to break down the calcium deposits down. In terms of general biological and medical literature, the fact that PTH can cause calcium accumulation to be resorbed back into the blood is already a very well known point.
Parathyroid hormone accomplishes its job by stimulating at least three processes:
- Mobilization of calcium from bone: Although the mechanisms remain obscure, a well-documented effect of parathyroid hormone is to stimulate osteoclasts to reabsorb bone mineral, liberating calcium into blood.
- Enhancing absorption of calcium from the small intestine: Facilitating calcium absorption from the small intestine would clearly serve to elevate blood levels of calcium. Parathyroid hormone stimulates this process, but indirectly by stimulating production of the active form of vitamin D in the kidney. Vitamin D induces synthesis of a calcium-binding protein in intestinal epithelial cells that facilitates efficient absorption of calcium into blood.
Excessive secretion of parathyroid hormone is seen in two forms:
- Primary hyperparathyroidism is the result of parathyroid gland disease, most commonly due to a parathyroid tumor (adenoma) which secretes the hormone without proper regulation. Common manifestations of this disorder are chronic elevations of blood calcium concentration (hypercalcemia), kidney stones and decalcification of bone.
- Secondary hyperparathyroidism is the situation where disease outside of the parathyroid gland leads to excessive secretion of parathyroid hormone. A common cause of this disorder is kidney disease – if the kidneys are unable to reabsorb calcium, blood calcium levels will fall, stimulating continual secretion of parathyroid hormone to maintain normal calcium levels in blood. Secondary hyperparathyroidism can also result from inadequate nutrition – for example, diets that are deficient in calcium or vitamin D, or which contain excessive phosphorus (e.g. all meat diets for carnivores). A prominent effect of secondary hyperparathyroidism is decalcification of bone, leading to pathologic fractures or “rubber bones”.
There is no doubt that chronic secretion or continuous infusion of parathyroid hormone leads to decalcification of bone and loss of bone mass. However, in certain situations, treatment with parathyroid hormone can actually stimulate an increase in bone mass and bone strength.
Analysis & Interpretation:
Another great resource I have used to learn more about the Parathyroid Hormone is the website Parathyroid.com. The thing is that one can stimulate calcium mineral deposits to break apart using the PTH. If you can extract enough calcium, the bones turn into “rubber” (or become very easy to fracture as well) which means that we can then probably stretch the bones.
I had already concluded in two previous, pivotal posts that the compound PTHrP (Parathyroid Hormone related Peptide) is most likely the key to induce the first step for adults with no cartilage to possibly dissolve the hard bone matrix for cartilage replacement using other growth factors with more chondrogenic effects. This post seems to put more anecdotal, but still weak evidence in showing that either PTH or PTHrP can be used for our ultimate goal of achieving bone lengthening after the cartilages completely disappear.
It seems that we have quite a few ways to demineralize bone and give it just enough elastic properties to strength the bones.
I like to conclude this pivotal post with the link for how one can actually turn bone into rubber-like using vinegar for an elementary school science project.