A Suggested Idea On How We Can Theoretically “Reopen” The Closed Growth Plates

A Suggested Idea On How That We Can Theoretically “Reopen” The Closed Growth Plates

I have said multiple times that it would be next to impossible within this century to create any type of technology to ‘reopen’ fully closed growth plates, at least completely non-invasively. That has been my opinion for a long time since I really started to understand how human bones really work and are organized. Unless there is some type of radical biomedical technology I am not aware of that is coming down the pipeline in the next few decades, I would not be looking for a completely non-invasive way to get the growth plates back.

However, I did recently read an article which seems to suggest at a very theoretical level that it might be possible to kind of “reopen” the closed growth plates, but it would still not be completely non-invasive. Refer to the paper “Roles of neutrophil-mediated inflammatory response in the bony repair of injured growth plate cartilage in young rats“. The PDF for the article is free for download.

I was made aware of the paper when I was trying to find relevant research that Cory Xian had done, since Tyler said that Xian was one of those people we should be following. This paper I did take the time to really look over extensively, and it just slightly hints at the idea that we might be able to change the progenitor cell lineage to something which it is not naturally supposed to go into.

Here is what you need to understand about the microbiological processes that seems to occur after the growth plates in a rat model were intentionally fractured and then analyzed.

Process #1: Inflammatory – This would be the initial injury induced inflammatory response, which is the automatic process that is activated when almost every part of the body is injured. What happens is that inflammatory cells, which comes in the types known as neutrophils, monocytes, lymphocytes, starts being rushed to the local area of injury. In terms of time, at least on the rat models, the first process lasts around 3 days, the maximum effect being around 1 day.

  • Process #2: Fibrogenic
  • Process #3: Osteogenic
  • Process #4: Bone Bridge Maturation

More Details On the Initial Inflammatory Response – The researchers have identified at least 5 different types of chemicals which will be stimulated to go towards the injury area. They include a chemokine, pro-inflammatory cytokines, and fibrogenic growth factors.

  • 1 type of neutrophil Chemotactic Chemokine – CINC-1
  • 2 types of Pro-inflammatory Cytokine – TNF-Alpha and IL-1Beta
  • 2 types of Fibrogenic Growth Factors – TGF-Beta1 and PDGF-B

What the researchers did was add a type of chemical which will decrease the number of neutrophil cell count. Quote: “Using an antirat neutrophil antiserum, a significant 60% reduction in neutro- phil count was achieved at the growth plate injury site”

(Side Note: The most interesting part of the neutrophil to pro-inflammatory cytokine stimulation is that while the antis-serum reduced the neutrophil count, it did not decrease the expression and numbers of the TNF-Alpha or the IL-1Beta (or the Fibrogenic Growth Factors like TGF-Beta1 and PDGF-B) . The reasoning is because besides the neutrophil expression increasing in the bone fracture site, there is two other types of cells which are rushed there, the monocytes and the lymphocytes, and the monocytes, which are also known as macrophage, are the other type of cells which really increase the expression of the Interleukin (IL-1Beta) and the tumor necrosis factor (TNF-Alpha). The results is that the number of MSCS which rushed to the local fracture sight was not not decreased. That suggested that the number of neutrophils in the growth plate injury sight had no real link to the amount of MSCs which will go to that growth plate injury area.)

The result of adding the chemical was that in the injury area, there was more bone tissue than cartilage tissue by ratio that had developed. This suggests that neutrophil cell types has the effect of at least shifting the osteogenic/chondrogenic ratio the other way. The researchers tested the osteogenic and chondrogenic gene expressors the SOX-9 and the COl-Type IIa and saw that the gene expressions were reduced. In reverse, the expression of bone cell differentiation transcription factor cbf-alpha1 and bone matrix protein osteocalcin, which create osteogenic tissue was increased.

If there is an injury aka fracture in the bones, the neutrophils would be able to help the fibrogenic growth factors to develop more cartilage progenitor type tissue and cells.

I quote the last sentence that is in the paper…

“These results suggest that an injury- induced, neutrophil-mediated inflammatory response may be involved in regulating downstream chondrogenic and osteogenic events, leading to bony tissue formation at the growth plate injury site; it appears to play a role in suppressing mesenchymal cell osteoblastic differentiation and increasing chondrogenic differentiation in the repair of injured growth plate cartilage”

It seems that one might be able to block the formation of bone bridges and keep the MSCs in the chondrogenic lineage if we could around the Fibrogenic or Inflammatory stage find some type of chemical to block the injury response processes from ever reaching the osteogenic stages.

It would be the pro-inflammatory cytokines the TNF-Alpha and IL-1Beta that we need to suppress while at the same type increase the number of neutrophils. The researchers did notices from their previous studies that if they did a local induction of chemokine IL-8 (or CINC-1 in rats) the neutrophil numbers would increase, but from past research, interleukin types are not good for cartilage tissue generation. The result of using the suggested IL-8 seems to be an increase in the macrophages in releasing the TNF-Alpha and IL-1Beta. So another chemical besides the IL-8 for neutrophil number increase would be needed. The researchers did say that The TNF-Alpha and the IL-1Beta are what will stimulate the fibrogenic growth factors to be stimulated so we might need to find a third compound to stimulate the fibrogenic growth factors while at the same time we decrease the levels of cytokine inflammation.

What ever chemical has that duo effect, when injected into the fracture area of a bone, might mean that cartilage type tissue, even if it is fibrocartilage in nature, would develop. Sure, we are talking about the growth plate response mechanism in rat models, but there is still some type of knowledge we can transfer for human application. If we do that, I believe that we might be able to create some type of pseudoepiphyseal cartilage layer, which can be slowly changed over time to be hyaline in nature, and then expanded for lengthening of the bones.

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