IGF-II , CNP, and HDAC4 inhibitors - wall of text - Height increase research.

[Wrecker]

I've been becoming a lot more active in height increase research, and I wanted to share a few of my findings to the community. I personally have not "been in the game" for too long, so please understand if I say something that doesn't particularly add up. I try my best, but I am by no means a scholar when it comes to this stuff.

Let's begin.

First, but not foremost (IMO) is IGF-2 . As much people talk about IGF-1 and it's role that is has in longitudinal bone growth, I believe that IGF-2 should not be entirely overlooked. If you take a look at this study, An essential role for IGF2 in cartilage development and glucose metabolism during postnatal long bone growth , it mentions that IGF-2 is strongly expressed in the proliferating zone of the growth plate, which is the hyaline cartilage if I am not mistaken. One issue I find with this though is, IGF2 is generally considered to play a key role in early fetal development, NOT in adulthood development being that a switch in expression levels makes IGF1 the dominant IGF in adulthood where it functions as a regulator for postnatal growth maintenance.. Though when we look at this next study - Spatial and temporal regulation of GH-IGF-related gene expression in growth plate cartilage, it mentions that the decrease in growth velocity that occurs with age may be caused, in part, by decreasing expression of IGF-II and increasing expression of type 2 IGF receptor and multiple IGFBPs..

So, IGF-2 is something that I've been personally looking at being that it isint always brought up.

The second thing I would like to bring to your attention is CNP, and the receptors of CNP. In this study - cGMP produced in response to ANP and CNP regulates proliferation and differentiation of osteoblastic cells, it mentions that natriuretic peptides (one of which being natriuretic peptide precursor C) were demonstrated to promote bone formation via the action of cGMP in a signal-transduction pathway mediated by specific receptors in osteoblast-like cells. This is why I believe that it should not be overlooked.

For those who don't know, the osteoblasts are cells that secrete the matrix for bone formation; this is why we want them to proliferate!

If you refer to this image, the osteoblasts are located in the perichondrium, and the chondrocytes are located in the hyaline cartilage - the area in the middle. We want more of BOTH... If you're heightmaxing.

-

Also, in this study, 8-Nitro-cGMP promotes bone growth through expansion of growth plate cartilage, it mentions that C-type natriuretic peptide (CNP) also positively regulates the elongation of bones through expansion of the growth plate cartilage. ALSO, 8-bromo-cGMP enhanced the growth of bones with expansion of hypertrophic zone of the growth plates without affecting either the width of proliferating zone or proliferation of chondrocytes. These results indicate that 8-nitro-cGMP formed in growth plate cartilage accelerates chondrocyte proliferation and bone growth.

8-bromo-cGMP, CNP, and cGMP are all things that I believe could be useful to know about when heightmaxing.


Lastly, but most DEFINITELY not least are HDAC4 inhibitors. The HDAC4 gene provides instructions for making an enzyme called histone deacetylase 4. This enzyme is part of a group of related enzymes, called histone deacetylases, that modify proteins called histones. In this study, MicroRNA-1 regulates chondrocyte phenotype by repressing histone deacetylase 4 during growth plate development, it mentions that HDAC4 negatively regulates chondrocyte hypertrophy by inhibiting Runx2, a critical transcription factor for chondrocyte hypertrophy. This is not good for heightmaxers! In the study they used MiR-1 ( Micro Rna - One ) to inhibit said gene ( HDAC 4) However, HDAC4 can be inhibited in other ways aswell.

In my personal opinion, HDAC4 could be inhibited to better enable the proliferation of chondrocytes.



TL;DR : I wonder if IGF-2 would benefit a heightmaxer. I'm pretty certain that 8-bromo-cGMP, CNP, and cGMP will be of use to a person wanting to increase height. Also, the inhibition of HDAC4 will better enable the proliferation of chondrocytes which is generally a good thing for a heightmaxer.




Kinda curious about what @Strike_Poseidon will think about the inhibition of HDAC4. It sounds kinda nice, tbh.

 

[Deleted member 2527]

Is any of this applicable after the age of 21?

 

[Tom2004]

just get LL

 

[Deleted member 4946]

I've been becoming a lot more active in height increase research, and I wanted to share a few of my findings to the community. I personally have not "been in the game" for too long, so please understand if I say something that doesn't particularly add up. I try my best, but I am by no means a scholar when it comes to this stuff.

Let's begin.

First, but not foremost (IMO) is IGF-2 . As much people talk about IGF-1 and it's role that is has in longitudinal bone growth, I believe that IGF-2 should not be entirely overlooked. If you take a look at this study, An essential role for IGF2 in cartilage development and glucose metabolism during postnatal long bone growth , it mentions that IGF-2 is strongly expressed in the proliferating zone of the growth plate, which is the hyaline cartilage if I am not mistaken. One issue I find with this though is, IGF2 is generally considered to play a key role in early fetal development, NOT in adulthood development being that a switch in expression levels makes IGF1 the dominant IGF in adulthood where it functions as a regulator for postnatal growth maintenance.. Though when we look at this next study - Spatial and temporal regulation of GH-IGF-related gene expression in growth plate cartilage, it mentions that the decrease in growth velocity that occurs with age may be caused, in part, by decreasing expression of IGF-II and increasing expression of type 2 IGF receptor and multiple IGFBPs..

So, IGF-2 is something that I've been personally looking at being that it isint always brought up.

The second thing I would like to bring to your attention is CNP, and the receptors of CNP. In this study - cGMP produced in response to ANP and CNP regulates proliferation and differentiation of osteoblastic cells, it mentions that natriuretic peptides (one of which being natriuretic peptide precursor C) were demonstrated to promote bone formation via the action of cGMP in a signal-transduction pathway mediated by specific receptors in osteoblast-like cells. This is why I believe that it should not be overlooked.

For those who don't know, the osteoblasts are cells that secrete the matrix for bone formation; this is why we want them to proliferate!

View attachment 526440

If you refer to this image, the osteoblasts are located in the perichondrium, and the chondrocytes are located in the hyaline cartilage - the area in the middle. We want more of BOTH... If you're heightmaxing.

-

Also, in this study, 8-Nitro-cGMP promotes bone growth through expansion of growth plate cartilage, it mentions that C-type natriuretic peptide (CNP) also positively regulates the elongation of bones through expansion of the growth plate cartilage. ALSO, 8-bromo-cGMP enhanced the growth of bones with expansion of hypertrophic zone of the growth plates without affecting either the width of proliferating zone or proliferation of chondrocytes. These results indicate that 8-nitro-cGMP formed in growth plate cartilage accelerates chondrocyte proliferation and bone growth.

8-bromo-cGMP, CNP, and cGMP are all things that I believe could be useful to know about when heightmaxing.


Lastly, but most DEFINITELY not least are HDAC4 inhibitors. The HDAC4 gene provides instructions for making an enzyme called histone deacetylase 4. This enzyme is part of a group of related enzymes, called histone deacetylases, that modify proteins called histones. In this study, MicroRNA-1 regulates chondrocyte phenotype by repressing histone deacetylase 4 during growth plate development, it mentions that HDAC4 negatively regulates chondrocyte hypertrophy by inhibiting Runx2, a critical transcription factor for chondrocyte hypertrophy. This is not good for heightmaxers! In the study they used MiR-1 ( Micro Rna - One ) to inhibit said gene ( HDAC 4) However, HDAC4 can be inhibited in other ways aswell.

In my personal opinion, HDAC4 could be inhibited to better enable the proliferation of chondrocytes.



TL;DR : I wonder if IGF-2 would benefit a heightmaxer. I'm pretty certain that 8-bromo-cGMP, CNP, and cGMP will be of use to a person wanting to increase height. Also, the inhibition of HDAC4 will better enable the proliferation of chondrocytes which is generally a good thing for a heightmaxer.




Kinda curious about what @Strike_Poseidon will think about the inhibition of HDAC4. It sounds kinda nice, tbh.

Runx2 is not good for heightmaxxing, which induces terminal differentiation of chondrocytes to osteoblasts, therefore finishing one chondrogenesis cycle, the key to this is to have a higher density of proliferative chondrocytes before they undergo hypertrophy and then when they do go through hypertrophy, that hypertrophy is enhanced. Anyway, none of this will work if you haven't already reversed and/or delayed senescence because your resting zone chondro progenitors have a finite replicative capacity, you fix that with DNA methylation (and even recover it) expect unlimited height growth however this process is slow...

As for IGF-2, good that you mention that, that would be pretty good, anyway, we don't actually want osteoblast proliferation for best growth potential as that just makes ossification faster, sox9 is what you should be enhancing ALL THE TIME while inhibiting Runx2, and no HDAC4 inhibitors won't help anything for the proliferation of chondrocytes, you just said it assists hypertrophy, there are various other factors which can assist hypertrophy and trust me RUNX-2 is the worst one as it causes the terminal differentiation of those chondrocytes, turning them into the ossified bone.

Also no, the proliferating zone of the growth plate is not the hyaline cartilage, that is the resting zone, the proliferating zone of the growth plate is literally called the proliferative zone

Also as for the CNP effects, meclozine does that just as well if not better as it targets the ERK node and ERK node is it what expands the hypertrophic zone, as for 8-bromo-cGMP that expands the growth plate as a whole, that can be induced with nitric oxide and Kidney secreted bone growth factors (Ecdysterone and BMP formula), I had that part covered a LONG time ago, at this point I think the only useful part of this is IGF-2 but that growth factor is barely used endogenously for postnatal longitudinal bone growth so we would need to get it exogenously, nevertheless, it is very effective!

 

[Wrecker]

Runx2 is not good for heightmaxxing, which induces terminal differentiation of chondrocytes to osteoblasts, therefore finishing one chondrogenesis cycle, the key to this is to have a higher density of proliferative chondrocytes before they undergo hypertrophy and then when they do go through hypertrophy, that hypertrophy is enhanced. Anyway, none of this will work if you haven't already reversed and/or delayed senescence because your resting zone chondro progenitors have a finite replicative capacity, you fix that with DNA methylation (and even recover it) expect unlimited height growth however this process is slow...

As for IGF-2, good that you mention that, that would be pretty good, anyway, we don't actually want osteoblast proliferation for best growth potential as that just makes ossification faster, sox9 is what you should be enhancing ALL THE TIME while inhibiting Runx2, and no HDAC4 inhibitors won't help anything for the proliferation of chondrocytes, you just said it assists hypertrophy, there are various other factors which can assist hypertrophy and trust me RUNX-2 is the worst one as it causes the terminal differentiation of those chondrocytes, turning them into the ossified bone.

Also no, the proliferating zone of the growth plate is not the hyaline cartilage, that is the resting zone, the proliferating zone of the growth plate is literally called the proliferative zone

Also as for the CNP effects, meclozine does that just as well if not better as it targets the ERK node and ERK node is it what expands the hypertrophic zone, as for 8-bromo-cGMP that expands the growth plate as a whole, that can be induced with nitric oxide and Kidney secreted bone growth factors (Ecdysterone and BMP formula), I had that part covered a LONG time ago, at this point I think the only useful part of this is IGF-2 but that growth factor is barely used endogenously for postnatal longitudinal bone growth so we would need to get it exogenously, nevertheless, it is very effective!

Hello, sorry for the late reply.

Firstly, I want to thank you for the learning opportunity. Rather than being bashed for a mistake I made, a learning opportunity was created; I really appreciate it. Anyhow, you mention exogenous igf-2.. I am unsure if you're attempting to go for a cost effective / " bang for you buck" stack, though from what I understand IGF-2 , and I mean HIGH QUALITY IGF-2 can be kinda expensive.... Do you believe that it IGF-2 could be best used as an auxiliary compound, or is it really worth every penny in terms of height growth? I don't know if you can answer that being that not many people are using IGF-2 on .me, though it's something to think about nonetheless.

Also, you brought up Runx2 and how it's inhibition is important... Have you ever looked into CADD522? CADD522 negatively regulated transcription of RUNX2 target genes such as matrix metalloproteinase-13, vascular endothelial growth factor and glucose transporter-1, but upregulated RUNX2 expression by increasing RUNX2 stability..... I am unsure if increasing the stability of RUNX2 is good or bad here in terms of gene expression... Isint the idea to simply deregulate the expression of RUNX2? If so extra stability may not be a problem.... Though I am really not an expert when it comes to this..... Just an independent learner.

Characterization of CADD522, a small molecule that inhibits RUNX2-DNA binding and exhibits antitumor activity

The RUNX2 transcription factor promotes breast cancer growth and metastasis through interactions with a variety of cofactors that activate or repress target genes. Using a direct drug discovery approach we identified CADD522 as a small molecule that inhibits ...

www.ncbi.nlm.nih.gov