Monthly Archives: December 2012

HELP WANTED: The Website Needs Chinese And Korean Translators And Detectives To Translate And Find Scientific PubMed Study Articles

imgresWhat I am noticing a lot recently is that some of the more interesting article posts are written in languages which I can not read (yet). So I am throwing a post out there looking for a people who can read, and translate Chinese and Korean scientific studies, articles, and papers.

Sometimes I come across papers in German, or Finnish, or Japanese but some of the more recent ones which I find the most interesting are both hard to find a complete full document file and text on as well as being in a language which I can’t read.

So there is two job roles that I hope people can take on to help make a contribution to the cause.

  • I would like people to first go to  The Library section on where they can get just The Abstract, but still need the full document. The articles that are in another language are always in brackets, which is a nice thing that the PubMed database has already done, to indicate to native English readers that the paper is in another language.
  • Then hope you can translate (you can use Google translate, Yahoo Babelfish, etc.) the documents completely, at least the introduction, discussion, and conclusion parts. The experimental, and method sections can be left untranslated, until we are sure that the experiment showed success in what we are hoping for.

I am willing to pay for these documents if there is a database somewhere which does hold them and require payment. However I prefer not to expend the effort, energy, and time to find these key papers/ documents. That hopefully would be the job of a person who would like like to make a contribution to the website.

At this point I can’t pay anything to the person who does this. The only thing I can do at this point is give them credit and put their name on any posts and papers we the researchers would write about.

China Military Hospital Research Clinics Have Already Engineered Functional Epiphyseal Growth Plates (Breakthrough)

I think it is time to reveal to the readers that what I had hypothesized in previous posts like A Real Alternative To Limb Lengthening Surgery – Epiphyseal Growth Plate Regeneration, Regrowth, Implantation, And Transplantation Is Completely Possible (Big Breakthrough!)” already was being done in countries like China has been occurring already.

I remember going really fast through the PubMed studies long ago and tabulate everything into The Library and there were a few studies which I was suspicious about. Two studies I went through today revealed that the Chinese Government and Military have been successful in actually regrowing fully functional epiphyseal growth plates, have tested them on laboratory rabbits, and have shown the plates are functional in vivo after implantation.

Study #1: [The treatment of premature arrest of growth plate with a novel engineered growth plate: experimental studies]. – Author: Zhou Y, Lu S, Wang J, Zhang Y, Huang J. –  Source: General Hospital, Chinese People’s Liberation Army, Beijing 100853, China.

Abstract
OBJECTIVES:
To observe the role of the engineered growth plate (EGP) in the treatment of premature arrest of growth plate and to establish a novel treatment method for the premature arrest of the growth plate.

METHODS:
The engineered growth plates were cultured for the first time by using polylactic acid (PLA) as cell scaffold seeded with growth plate chondrocytes and they were implanted into the medial proximal defects of growth plates of New Zealand rabbit tibia. The degree of deformity of the tibia was evaluated by X-ray and the expression of collagen II mRNA of regenerating growth plate was detected by in situ hybridization technique.

RESULTS:
Little deformity appeared in the EGP group 8 weeks after operation. Some deformity was seen in the EGP group 16 weeks after operation, whereas it’s degree was much less than that of the control group (P = 0.0001). The degree of the angular deformity of the EGP precultured with bFGF and TGF-beta group was less than that of the EGP group (P < 0.05). The cells in the regenerating growth plate arranged in column and were stained blue by in situ hybridization technique.

CONCLUSION:

The EGP can prevent the formation of bony bridge and restore the growth of the damaged growth plate.

PMID: 11832153 – [PubMed – indexed for MEDLINE]Study #2: [Repair of upper tibial epiphyseal defect with engineered epiphyseal cartilage in rabbits]. – Author: Zhou Q, Li QH, Dai G. – Source: Department of Orthopaedics, Southwest Hospital, Third Military Medical University, Chongqing, P. R. China 400038.

Abstract
OBJECTIVE:
To observe the effect of engineered epiphyseal cartilage regenerated in vitro with 3-D scaffold by chondrocytes from epiphyseal plate in repairing the tibial epiphyseal defect, and to explore the methods to promote the confluence between engineered cartilage and epiphyseal plate.
METHODS:
Chondrocytes were isolated enzymatically from the epiphyseal plates of immature rabbits, and then planted into the tissue culture flasks and cultivated. The first passage chondrocytes were collected and mixed fully with the self-made liquid biological gel at approximately 2.5 x 10(7) cells/ml to form cell-gel fluid. The cell-gel fluid was dropped into the porous calcium polyphosphate fiber/poly-L-lactic acid(CPPf/PLLA)scaffold, and a cell-gel-scaffold complex formed after being solidified. The defect models of 40% upper tibial epiphyseal plate were made in 72 immature rabbits; they were divided into 4 groups: group A(the cell-gel-scaffold complex was transplanted into the defect and the gap filled with chondrocyte-gel fluid), group B (with noncell CPPf/PLLA scaffold), group C(with fat) and group D(with nothing). The changes of roentgenograph, gross and histology were investigated after 2, 4, 6, 8, 12 and 16 weeks of operation.

RESULTS:
In group A, the typical histological structure of epiphyseal plate derived from the engineered cartilage with a fine integration between host and donor tissues after 2 weeks. The repaired epiphyseal plate had normal histological structure without deformation of tibia after 4 weeks. The early histological change of epiphyseal closure appeared in the repaired area with varus and shortening deformation of the tibia after 8 weeks. The epiphyseal plate was closed in the repaired area with more evident deformation of tibia; the growth function of repaired epiphyseal plate was 43.6% of the normal one. In groups B, C and D, deformation of tibia occurred after 2 weeks; the defect area of epiphyseal plate was completely closed after 4 weeks. The deformation was very severe without growth of the injured epiphyseal plate after 16 weeks, and no significant difference was observed between the three groups.

CONCLUSION:
Engineered epiphyseal cartilage can repair the epiphyseal defect in the histological structure with partial recovery of the epiphyseal growth capability. Injecting the suspension of fluid chondrocyte-gel into the defects induces a fine integration of host and donor tissues.

PMID: 14663950   [PubMed – indexed for MEDLINE]

Study #3: [Repair of growth plate defects of rabbits with cultured cartilage transplantation]. – Author: Wang J, Yang ZM, Xie HQ. – Source: Department of Orthopedic Surgery, First University Hospital, West China University of Medical Sciences, Chengdu Sichuan, P. R. China 610041

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2001 Jan;15(1):53-6.
[Repair of growth plate defects of rabbits with cultured cartilage transplantation].

[Article in Chinese]
Wang J, Yang ZM, Xie HQ.
Source
Department of Orthopedic Surgery, First University Hospital, West China University of Medical Sciences, Chengdu Sichuan, P. R. China 610041.

 

Abstract
OBJECTIVE:
To prevent early closure of growth plate and developmental deformities of limbs by allografts of cultured cartilages into growth plate defects of rabbits.

METHODS:
Chondrocytes isolated from articular cartilage of 1-month rabbits formed cartilage after cultivation in centrifuge tubes. The cartilages cultured for two weeks were implanted into growth plate defects of proximal tibiae of 6-weeks rabbits. At 4th and 16th weeks, X-ray, histologic and immunohistochemical examination were performed.

RESULTS:
The tibiae had no marked deformities after 4 weeks of operation. Histologic examinations showed that the defects were filled with cartilage. Immunohistochemical results of type II collagen were positive. The tibiae with allografts of cultured cartilages had no evident deformities after 16 weeks of operation. Histologic examination showed nearly closure of growth plates. On the contrary, the tibiae on control side formed severe deformities and growth plate were closed.

CONCLUSION:
Allograft of cultured cartilages into growth plate defects may replace lost growth plate tissues, maintain normal growth of limbs and prevent developmental deformity.

PMID: 12563933 [PubMed – indexed for MEDLINE]

Interpretation: I would say that by now, it is clear that the chondrocyte that is extracted from young lab animals and than transplanted into older individuals through allograft is functional. While it is true that the epiphyseal cartilage that they grew from scaffold with chondrocytes embedded is not completely functional, I would suspect it is either because they can’t get the right mixture of growth factors or can’t get the chondrocytes to stack correct in the right direction. The whole purpose of these military hospital clinics are supposed to be to correct for pediatric limb growth deformities by implanting these epiphyseal cartilages into the broken cartilage  but it would not be hard and may only take a few years for them to grow these cartilage to a scale which would be enough to be put into human limbs.

I would be the first to admit that the therapy for transplanting and embedding grown growth plates is still being worked out, as clearly stated by paper “[Advance on repair of growth plate injury].” I would say that within 10-20 years, the Chinese government will get the cartilage they have regrown to work completely functionally with the right amount of strength to prevent possible cartilage collapse and get the stacking direction correctly. . When that happens, they will take the cartilage regeneration technology, and start putting them into its own military soldiers to make them taller.

A Final Message For The Year 2012, What Is In Store For Natural Height Growth In 2013

I want to thank all of you for being a part of this website and the project/ endeavor. Natural Height Growth was started only 5 months ago around the middle of July and in almost half a year, the website has been slowly growing and attracting new people each day.

Come back and join in the project next year in 2013 as I and the other height increase researchers continue in our progress in searching. What I would love to do is start to move away from the theoretical by the middle of next year after “The Library” section has been completely stacked with all the articles, studies, and papers we can find on anything related to growth plates, chondrocytes, cartilage, and how to possibly manipulate them. There really is only so much information that can be available on the internet on this very small niche/ subject.

Maybe you can find new sites for me and the other researchers to look through. If you find useful or interesting supplements, devices, or height increase claims, leave an email and I will look at it. Some of the posts I have been writing recently are from ideas, websites, and products the regular readers have been suggesting to me.

This website I plan to leave up for at least 10 years, while constantly editing, adding new information, rearranging, all to make it better for the first time visitor and the regulars.

This is the type of internet resource I would have LOVED to have had years ago when I was going through that phase where I wanted to really grow taller. I realized that the internet and the world was missing something that was not being provided for, and I have been trying to solve that problem, and create a resource that everyone can use and learn from.

The frequency and rate of the posts will be lower now that I am understanding more of the physiology of the human body. It is time to shift from quantity towards quality in the content I write up. If you go back to my older posts, it is very noticeable that the posts were not very good. Ove time the posts have been getting slightly better.

The podcasts series is going well and I have been interviewing many of the people I was hoping to talk to however many questions still exist.

I hope to hire a website developer next year to make the website even more streamline and make it faster. The website is getting slower.

As for the LSJL device, I currently have put that idea on hold while I get this website in a better condition so that it can be more self sustaining, without the need of me to always be watching over it’s operations. Once the website is running more smoothly, I’ll work more on the LSJL device and have it built.

I want to (not that I will if legal and government issues force me not to) focus on doing real experiments by the middle of next year with buying Genotropin, Anavar, Letrazole, etc. from companies like SinoHGH and testing them in chondrocyte and hyaline cartilage mediums. I will be trying to buy some growth factors like BMP-2, BMP-7 from the company ProSpecOne of the reasons I have been talking about biohacking is that I would like to set up biological and genetic experiments to test for the effectiveness of these compounds.  With all of these things, it’ll be very expensive for me to get the equipment to do real testing like the histology work, the measurements with calipers, the stain blotting to track physeal lengthening, etc.

Why Do You Really Want To Grow Taller And Increase Your Height? What Is The Real Reason?

qmarkI have been telling you guys the readers a lot about my story, about my history, and my thoughts and reasons on why I am so obsessed with height and my desire to be taller. You have seen me expose my insecurities, anxieties, worries, and pain that I have felt and experienced in life.

I am living the type of life these days where I am completely honest to everyone I meet since I feel like so much of my life I have been hiding, lying, and trying to bullshit my way just to get by society and the need to play all these socially imposed rules I am forced to follow. The incredible anxiety filled need to always be keeping up a fake mask to hide my real self has been melted off to reveal who I am. I have been deceiving everyone for so long, but especially myself. Right now, there is no where else I’d rather be than to write this post and upload it for the readers who regularly come to the website and read the posts.

When I am completely honest, I feel free, I find that I am doing my best work ,and also that I am more successful in my businesses and financially. Life has been improving drastically.

As this will be one of the last posts of the year, I wanted to leave this post as a way for you the reader to finally (and hopefully) get a chance to tell me, and some of the other readers, your personal reason on why you are so intent on growing taller and increasing your height.

I know that I personally had to ask this question to myself AT LEAST 10 times “WHY?” until I could really get deep enough and to the real problem I was having the real pain I felt. It took me at least 2 hours of introspection, deep self analysis, and some walking meditation in the outdoors for me to really become honest about my faults, my insecurities, and fears about about being too short. I wrote very early on in a post entitled “Height Is The Last Frontier For Personal Development” that I felt that in terms of what the modern human can change about themselves, their height may be the last factor which they still can’t really change, without taking some really drastic action and expend a great number of resources. We can change nearly everything about ourselves these days, except for this last thing.

The thing is that I have already asked this question to the readers before in an earlier post entitled “What Is Your Reason To Seek Height Increase?” but there was no replies, and the post was rather short (pun intended) so I wanted to try again, to get some feedback from the readers again. How can I serve you better and help resolve your height issues and fears? What pains in your life related to size and stature do you feel? The key is to realize that I/you are not lying to myself/yourself, or trying to say somethat that may be politically correct but don’t really reflect what you really feel or think about inside.

So…

“Why Do You Really Want To Grow Taller And Increase Your Height? What Is The Real Reason?”

So please, leave a message and comment to either the bottom of this post or to the website email naturalheightgrowth@gmail.com and tell the height increase researchers what have been your reasons, issues, and “WHY?” you have been so dedicated and focused in increasing your height.

Natural Height Growth December 2012 – Monthly And End Of Year Website Traffic Data Report

Note: To see the report from last month, go to “Natural Height Growth November 2012 – Monthly Website Traffic Data Report.”

One of the features I wanted to add to this website was to show the readers how far and big the website has managed to reach from it’s birth. I have been using the website traffic tracking programs Google Analytics and Clicky to determine how much and what type of traffic has been going through the website. These days I mainly only use Clicky because it has some features that Google Analytics just don’t provide (ie. real time live streaming traffic data). It is not free once you use it past a certain number of days or add a certain number of websites. For 1 year of coverage, I paid about $90. I personally think it was worth the service just to know what my websites are up to.

For this month’s report, since it is the last month of the year, I will be posting a little more information than usual. I will show both the Monthly and Yearly traffic data.

Analysis: If we now look at the data, we see that the daily visitors have increased from about 600 total visitors per day in November to about 800-850 total daily visitors per day in the last week or so. However there has been a 1 day where the traffic did go past the 900 visitors mark to around 930. At this rate, I hope that by next month the traffic will reach 1000 total daily visitors. What is been very consistent is the bounce rate, which has always been around the 24%-28% range. The average amount of time spent on the website is 3 min, 53 secs. Last month, the traffic was around 14,000 total visitors on the 30th. This month the traffic is 21,00o for the time to the 30th. This technically means that the traffic has increased by 50% from last month, which is about the same pattern we saw last month. The major website changes I did like add the supplement page and a complete formal exercise routine page, along with a “Start Here” page meant most of the traffic is going through those 3 pages now instead of just randomly ending up in the multiple pages. Like James/Hakker said in the last podcast episode, this website has many pages and it is very difficult to navigate around the place. I will have to figure out how to make the website easier to navigate around for next year.

For the month of December, from data range Dec. 1 – Dec. 30…

Screen Shot 2012-12-31 at 11.28.51 AM


Now for the yearly traffic statistics. Since the website/blog was started around the middle of July, The data range is from July 1 – Dec 30..

Analysis: We can see the website’s humble beginnings in July when I would get maybe 5-10 people to the blog everyday. That was the time when I would write as much as possible and post as much as possible everything I had learned and heard of in the years of knowledge I had accumulated. Sometimes I just enjoyed writing about my thoughts on height and how it affects the rest of society. What is very noticeable is that in the beginning of September, the 1st, the traffic on the website went up really high and was multiplied by 14X. At that time, the traffic to the site was around 100 total visitors a day.

A post on Tanya Angus I did coincided with a the US news networks all choosing to do a story on her story and condition. There pure coincidence my post was on the first page of google search results when you search about Tanya Angus’s height. That lead to traffic which went up to 150 visitors/hour. After that the traffic has been relatively calm and slowly increasing over time. In 5 months, a total of 48,700 unique visitors showed up to the website. The bounce rate is a small at 23% and the amount of time the average visitor spends is almost 4 minutes.

Screen Shot 2012-12-31 at 11.36.47 AM

 

 

Parathyroid Hormone And Parathyroid Hormone-Related Protein May Lead To Non-Invasive Epiphyseal Growth Plate Regeneration (Big Breakthrough)

This is one of those posts which I am not sure if I am interpreting the results correctly but if I am, I would say that it may lead to an entire area of research that we can go into and really have a good chance at causing epiphyseal growth plate regeneration in a minimal invasive approach.

Recently I came across a PubMed study which has made me question whether the entire growth plate physiology we have been learning may be missing a critical piece. That piece was that the distinct layers of the growth plate where the individual chondrocytes wll move through in its life cycle don’t just move in one direction, but can go also in reverse. The study is entitled “Parathyroid hormone [PTH(1-34)] and parathyroid hormone-related protein [PTHrP(1-34)] promote reversion of hypertrophic chondrocytes to a prehypertrophic proliferating phenotype and prevent terminal differentiation of osteoblast-like cells.

The abstract is below…

J Bone Miner Res. 1999 Aug;14(8):1281-9.

Parathyroid hormone [PTH(1-34)] and parathyroid hormone-related protein [PTHrP(1-34)] promote reversion of hypertrophic chondrocytes to a prehypertrophic proliferating phenotype and prevent terminal differentiation of osteoblast-like cells.

Zerega B, Cermelli S, Bianco P, Cancedda R, Cancedda FD.

Source

Istituto Nazionale per la Ricerca sul Cancro, Centro di Biotecnologie Avanzate, Genova, Italy.

Abstract

The effects of parathyroid hormone/parathyroid hormone-related protein (PTH/PTHrP) on late events in chondrocyte differentiation were investigated by a dual in vitro model where conditions of suspension versus adhesion culturing are permissive either for apoptosis or for the further differentiation of hypertrophic chondrocytes to osteoblast- like cells. Chick embryo hypertrophic chondrocytes maintained in suspension synthesized type II and type X collagen and organized their extracellular matrix, forming a tissue highly reminiscent of true cartilage, which eventually mineralized. The formation of mineralized cartilage was associated with the expression of alkaline phosphatase (ALP), arrest of cell growth, and apoptosis, as observed in growth plates in vivo. In this system, PTH/PTHrP was found to repress type X collagen synthesis, ALP expression, and cartilage matrix mineralization. Cell proliferation was resumed, whereas apoptosis was blocked. Hypertrophic chondrocytes cultured in adherent conditions in the presence of retinoic acid underwent further differentiation to osteoblast-like cells (i.e., they resumed cell proliferation, switched to type I collagen synthesis, and produced a mineralizing bone-like matrix). In this system, PTH addition to culture completely inhibited the expression of ALP and matrix mineralization, whereas cell proliferation and expression of type I collagen were not affected. These data indicate that PTH/PTHrP inhibit both the mineralization of a cartilage-like matrix and apoptosis (mimicked in the suspension culture) and the production of a mineralizing bone-like matrix, characterizing further differentiation of hypertrophic chondrocytes to osteoblasts like cells (mimicked in adhesion culture). Treatment of chondrocyte cultures with PTH/PTHrP reverts cultured cells in states of differentiation earlier than hypertrophic chondrocytes (suspension), or earlier than mineralizing osteoblast-like cells (adhesion). However, withdrawal of hormonal stimulation redirects cells toward their distinct, microenvironment-dependent, terminal differentiation and fate.

PMID: 10457260   [PubMed – indexed for MEDLINE]

Analysis: While the study was done on chickens, I personally believe that the same PTH/PTHrP feedback loop is also seen in humans. It says very clearly that the PTH/PTHrP hormonal balance managed to inhibit the formation of compounds only the hypertrophic chondrocytes release, which are the Collagen Type X, the ALP, and mineralization. It says very clearly…”PTH/PTHrP was found to repress type X collagen synthesis, ALP expression, and cartilage matrix mineralization. Cell proliferation was resumed, whereas apoptosis was blocked.”

If we remember from studies we looked at in the past, specifically “BMP and Ihh/PTHrP signaling interact to coordinate chondrocyte proliferation and differentiation.” The two main points were…

  1. During endochondral ossification, two secreted signals, Indian hedgehog (Ihh) and parathyroid hormone-related protein (PTHrP), have been shown to form a negative feedback loop regulating the onset of hypertrophic differentiation of chondrocytes
  2. Overexpression of Ihh in the cartilage elements of transgenic mice results in an upregulation of PTHrP expression and a delayed onset of hypertrophic differentiation.

Screen Shot 2013-01-01 at 10.37.27 PMNow, let’s look at this other study entitled “The PTHrP–Ihh feedback loop in the embryonic growth plate allows PTHrP to control hypertrophy and Ihh to regulate proliferation

The abstract is below…

Growth plate and long bone development is governed by biochemical signaling pathways of which the PTHrP–Ihh system is the best known. Other factors, such as BMPs, FGFs and mechanical loading, may interact with this system. This study aims at elucidating the relative importance of PTHrP and Ihh for controlling proliferation, and hypertrophy in fetal growth plate cartilage. We assessed the question why reduced Ihh expression leads to more pronounced effects on the number of non-hypertrophic cells and total bone formation, compared to PTHrP down-regulation. Using few basic equations, constituted from literature data, this paper shows how the PTHrP–Ihh feedback system can control different aspects of tissue differentiation at distinct locations. In particular, it is shown that (mechanical or biochemical) perturbations will affect proliferation via Ihh-related parameters, whereas changes in PTHrP-related parameters selectively interact with hypertrophy. This is contra-intuitive, since PTHrP acts to keep cells proliferating. In this context, the critical PTHrP level for keeping cells proliferating has been reconsidered. In addition, an explanation is provided for the aforementioned difference in effect between reduced Ihh and PTHrP expression.

Screen Shot 2013-01-01 at 10.49.48 PMAnalysis: From just the abstract and the clipping, it would suggest that the PTHrP is the main component that is known today which determines how much the chondrocytes in the pre-hypertrophic layer and the proliferative layer can replicate. However, after I read further into the dicussion part of the study, it seems that the authors are suggesting that while the PTHrP and the iHH are in a feedback loop where they affect each other, they actually have different roles in different section where it is actually the iHH is what determines the proliferative capacity and the PTHrP is what determines the hypertrophic ability. Of course we have to realize that it would appear the scientists reached this conclusion from mathematical derivation in looking at local, very simplified concentration gradients.

Note to the readers:

  • The Ihh is expressed in the pre-hypertrophic chondrocytes
  • The PTHrP is expressed in the perichondrium
However, there is not denying the fact that the PTHrP does control the amount of ihh concentration and it is the what causes the first step in the entire feedback loop to initiate.
This study actually brought me back to another study, “Parathyroid hormone-related peptide expression in the epiphyseal growth plate of the juvenile chicken: evidence for the origin of the parathyroid hormone-related peptide found in the epiphyseal growth plate.“The abstract is below…

J Cell Biochem. 2001;80(4):504-11.Parathyroid hormone-related peptide expression in the epiphyseal growth plate of the juvenile chicken: evidence for the origin of the parathyroid hormone-related peptide found in the epiphyseal growth plate.

Medill NJ, Praul CA, Ford BC, Leach RM.

Source

Department of Poultry Science, 213 William L. Henning Building, The Pennsylvania State University, University Park, PA 16802, USA.

Abstract

Parathyroid hormone-related peptide (PTHrP) has been shown to be essential for normal endochondral bone formation. Along with Indian hedgehog (Ihh), it forms a paracrine regulatory loop that governs the pace of chondrocyte differentiation. However, the source of PTHrP for this regulatory loop is not clear. While one hypothesis has suggested the periarticular perichondrium as the source of PTHrP for growth plate regulation, other data utilizing immunohistochemistry and in situ hybridization would indicate that growth plate chondrocytes themselves are the source of this peptide. The data described in this report supports the view that postnatal growth plate chondrocytes have the ability to synthesize this important regulatory peptide. Immunohistochemistry of tissue sections showed that PTHrP protein was evident throughout the chick epiphysis. PTHrP was seen in chondrocytes in the periarticular perichondrium, the perichondrium adjacent to the growth plate, the prehypertrophic zone of the growth plate, and the hypertrophic zone of the growth plate. However, cells in the proliferative zone, as well as some chondrocytes in the deeper layers of articular cartilage were predominantly negative for PTHrP. PTHrP was detected by Western blotting as a band of 16,400 Da in extracts from hypertrophic chondrocytes, but not from proliferative cells. RT-PCR detected PTHrP mRNA in both proliferative and hypertrophic growth plate chondrocytes, as well as in articular chondrocytes. PTH/PTHrP receptor mRNA was detected by Northern blotting in growth plate, but not articular chondrocytes. Thus, we conclude that most of the PTHrP present in the epiphyseal growth plate of the juvenile chick originates in the growth plate itself. Furthermore, the presence of large amounts of PTHrP protein in the hypertrophic zone supports the concept that PTHrP has other functions in addition to regulating chondrocyte differentiation.

Copyright 2001 Wiley-Liss, Inc.

PMID: 11169734  [PubMed – indexed for MEDLINE]

Personal Interpretation: Let’s assume that the study on chickens is the same as humans, since the other PubMed studies done on lab animals like rats showed a similar negative paracrine feedback loop.  This means that we know where the Parathyroid hormone-related peptide is coming from, the growth plates themselves. Sure, they might be coming from somewhere else as well, like the adrenal glands or the thyroid glands, however the majority of the PTHrP that makes up the PTH/PTHrP and iHH loop comes from the growth plates. The PTH obviously comes from the parathyroid glands. The researchers found the PTHrP mRNA in two areas, the hypertrophic area, and the proliferative layer. We saw in the previous study that the researchers believed the PTHrP is coming from the perichondrium, closer to the articular cartilage region. However this study seems to disapprove that view.

The big thing that is very interesting is that you don’t find the PTHrP in the articular cartilage, but only the epiphyseal cartilage. 

Let’s now look at the Wikipedia article on the Parathyroid hormone related peptide. “It is occasionally secreted by cancer cells (breast cancer, certain types of lung cancer including squamous cell carcinoma)…It regulates endochondral bone development by maintaining the endochondral growth plate at a constant width….PTHrP is related in function to the “normal” parathyroid hormone. When a tumor secretes PTHrP, this can lead to hypercalcemia.[3] As this is sometimes the first sign of the malignancy.”

From the Wikipedia article on Hypercalcemia, we learn that hypercalcemia is “is an elevated calcium level in the blood.” How this condition is related back to the PTH/PTHrP where the PTH/PTHrP ratio and balance has a main function where it controls how much calcium is supposed to either be in the blood stream or be absorbed to the inorganic bone matrix making it harder.

In my personal research I have actually found a weak inverse correlation between bone density and bone length. Since the calcium absorption to the bone is correlated to bone density, if the PTHrP is causing the calcium to be lost from the bone matrix, that means that the bone is weaker, so it is weaker allowing it to be more easily modified (ie. lengthened). What is given is that its mechanical properties which measure strength of the bone is smaller.

Remember also that we have found a rather strong correlation between great height and increase cancer risk. What I believe is that we have found the very first major compound which can lead to possible epiphyseal plate regrowth en vivo/ endogenously. However a huge warning must be put to this post because of the nature of what we are intending to do. Nature is wise in keeping humans and other animals to a certain size. It has many mechanisms that turn on so that e don’t overgrow out of bounds. Technically, any growth of bone size after cartilage closure probably has an extremely high risk and chance for developing into forms of cancer.

The idea is really just get more PTHrP into the growth plate, since it seems to have a positive correlation to keeping the growth plate thickness intact, and has the ability to reverse the hypertrophic chondrocytes back to the proliferative stage. This means that the growing age range can be extended, as long as the person has some chondrocytes in the resting zone left. The idea is to use two types of injection needles. One is to add new progenitor cells into the resting zone so that there will be more initial raw material (ir. progenitor chondorcytes) to work with. The 2nd injection is the PTHrP, which would cause the chondrocytes to focus more on proliferation and actually keep them from hypertrophizing. The 3rd injection would be for the iHH which would cause the iHH expression to increase and push the process of chondrocye differentiation back. Adding a fourth injection of other growth factors like BMPs and FGF-2 would lead to the chondrocytes to proliferate even more. All that is required after that is for the chondrocytes to reach past the endochondral layer and get to the outside to get a chance to push in the right direction. If we do not keep the growth direction correctly, it could lead to just forms of chondrocsarcoma and osteosarcoma.

This method to regrow the plate over again is the first time I have seen that the width of the plate can be increased again. The fact that it says very clearly in the Wikipedia article that the PTHrP is secreted by cancer cells shows that this is the type of compound that would be needed to restart the cartilages again.