Category Archives: Uncategorized

Huge Breakthrough study-hypertophic chondrocytes transdifferentiate into osteoblasts

This is a study that could have massive ramifications on height increase but the the exact mechanism is unknown.  But that cells that have the genetic material of growth plate cells are retained in adult bone is huge news.

Hypertrophic chondrocytes can become osteoblasts and osteocytes in endochondral bone formation.

hypertrophic chondrocytes<-full study

“Chondrocytes and osteoblasts are considered independent lineages derived from a common osteochondroprogenitor. In endochondral bone formation, chondrocytes undergo a series of differentiation steps to form the growth plate, and it generally is accepted that death is the ultimate fate of terminally differentiated hypertrophic chondrocytes (HCs). Osteoblasts, accompanying vascular invasion, lay down endochondral bone to replace cartilage.  [Can] HC become an osteoblast and contribute to the full osteogenic lineage? Here we use a cell-specific tamoxifen-inducible genetic recombination approach to track the fate of murine HCs and show that they can survive the cartilage-to-bone transition and become osteogenic cells in fetal and postnatal endochondral bones and persist into adulthood. This discovery of a chondrocyte-to-osteoblast lineage continuum revises concepts of the ontogeny of osteoblasts, with implications for the control of bone homeostasis and the interpretation of the underlying pathological bases of bone disorders.”

This is huge because it means that the transdifferentiated osteoblasts retain some of the chondrocytic genetic material which means they could possibly dedifferentiate back into chondrocytes!

“The expression of preosteoblastic markers in LHs before the formation of the POC raises the possibility that these cells may transition to an osteoblastic fate”

“HC-Derived Cells Are Present in Fetal, Neonatal, and Adult Bone.”

“The HC-derived cells, morphologically resembling osteoblasts, were found close to the chondro-osseous junction, on the surface of trabeculae, and in the endosteum”<-that means they are in a good position to be involved in neo growth plate formation.

“HC[hypertrophic chondrocytes] Derivatives Transit to the Primary Spongiosa and Become Col1a1-Expressing Cells.”<-the majority of HC derivatives become osteoblasts.

“HC-to-bone transition occurs during postnatal bone growth and that HC-derived cells may be long-lived within the mature bone”

Here’s an image of the HC lineage:

hypertrophic chondrocyte lineage

“The reversion of HCs to a prehypertrophic- like state in response to endoplasmic reticulum (ER) stress suggests that hypertrophy is not an irreversible state in vivo”<-Could we revert HC-derived osteoblasts back to hypertrophic chondrocytes back to pre-hypertrophic cells to reform growth plates.

(Michael: That actually makes a lot of sense if one thought about it. It can’t be all dead inorganic bone ECM matter where the physeal cartilage turns into bones (aka Primary Spongiosa). How would bone cells even be able to travel to that middle-region later on if the chondrocytes completely died out and the lucanae was covered by calcium minerals. For the smooth gradual transition from the hypertrophic layer to the vascularization/calcification layer to the mineralization layers to work out, there would be some minority of chondrocytes which would change identities. If all the chondrocytes died out and the layer of the lucanae was completely mineralized, I would not be sure that osteoblasts would be able to reach the primary spongiosa layer.

Here is what I have found years ago. (Source: Chondrogenesis just ain’t what it used to be) Prehypertrophic chondrocytes secrete IHH while the chondrocytes from the perichondrium secrete PTHrP, which effect the PTH/PTHrP receptors which are on the prehypertrophic chondrocytes. In addition, we have to consider the effects of the VEGF. VEGF is secreted by hypertrophic chondrocytes, and that it acts as a major inducer of vascular invasion.

The big thing is the following…

“…demonstrated that Ihh is not only required for chondrocyte hypertrophy, but also for expression of Cbfa1, a transcription factor required for osteoblast differentiation”

If the molecular biologist researchers have been able to identify all of the  major players which causes the chondrocytes to go into apoptosis, and also transdifferentiation, then we at least know which transcription factors causes the changes. I suspect it is Cbfa1.

Refer also the seminal work “Indian hedgehog couples chondrogenesis to osteogenesis in endochondral bone development”

That study proved conclusively that it is IHH that starts everything. IHH stimulates the Cbfa1, which causes the vascularization. I am going to make a guess that somewhere along the way, the two peptides also caused the transdifferentiation.

So how do we actually figure out what type of chemical would lead the osteoblast/osteocytes types to go in reverse and de-differentiate aka some type of reverse transdifferentiation?

We first have to assume that there is some type of external stimuli (mechanical, chemical, electrical) which would be able to even do the de-differentiation.

I propose this idea for Tyler…

Let’s assume that if we change the environment, the cell will start to change its identity. Remember the study which showed that the path which the MSCs will differentiate into can be determined by the shape of space that they are placed into? That suggest that if we change the environment that the osteoblasts/bone cells are in, maybe they will change as well.

Here is my first idea: I propose that we try to remove the calcium crystals/de-mineralize the area. To do that, remember that the PTH and the PTHrP balance from the parathyroid glands controls the level of calcium that is dissolved into the human blood (refer to “Chapter 5 – The parathyroid glands and vitamin D“)

“In bone, within 1 or 2 hours, PTH stimulates a process, known as osteolysis, in which calcium in the minute fluid-filled channels (canaliculi/lacunae) is taken up by syncytial processes of osteocytes and transferred to the external surface of the bone and, thence, into the extracellular fluid. Some hours later, it also stimulates resorption of mineralized bone; a process that releases both Ca2+ and Pi into the extracellular fluid. The Pi is rapidly removed from the circulation because the most dramatic effect of PTH on the kidney is to inhibit reabsorption of Pi in the proximal tubule and markedly increase its excretion“

Let’s increase the level of PTHrP in the local region, which is what I had proposed in a post I had written more than a year ago (The Connection Between Regenerating Deer Antlers and The PTHrP, PTH And IHH pathway for Cartilage Regulation, PTHrP Seems To Be The Answer (Big Breakthrough!)). Decrease the concentration of CA2+ from the ECM, and see what happens to the osteoblasts. Would they de-differentiate into chondrocytes if their environment changes?

It might be that the formation of osteoblasts and the increased levels of mineralization/vascularization/calcification is a positive feed back loop where each part feeds upon itself, which is initialized by VEGF. If we break the positive cycle at the process of mineralization, would the osteoblasts also go in reverse?

The Problems From Using Growth Hormone Therapy To Make Growing Children Taller

The Problems From Using Growth Hormone Therapy To Make Growing Children Taller

In a recent post that the heightism blogger Geoffrey Arnold wrote in the r/short subreddit, he made a point on the limitations of growth hormone therapy to treat idiopathic short stature. On a certain level, he is right. However, there is more to the science than just reading the Abstracts to PubMed articles, which I have found many people already do ie. Bodybuilders, and amateur researchers. He is well read, but not at a level of a person who has gone deeper into the details.

I refer to the post…
Growth Hormone Therapy

On his first claim, 99% of the time, he is correct, however there have been certain cases of individuals who did see a slight bit of increase in their adult height after using HGH, but it was almost always just 1 inch or so. I refer to someone actually well known in the online community, one of the founders/spokesperson of the website GoodLookingLoser.com The big muscled guy wrote in one thread that he did grow 1 full inch after he started to take growth hormones for his workouts to increase his muscle size. Many people responded saying that he couldn’t have since he was too old and his growth plates were fused, but he has stuck by his claims.

On his 2nd claim, he is only half right.

The thing is that children who are short statured which is caused by growth hormone deficiency will have a much more pronounced and dramatic boost in growth and final adult height from using growth hormones, but that does NOT mean that developing children with fully open epiphyseal growth plates who are short statured which is NOT caused by GH deficiency won’t see any height increasing results. That is where he is wrong.

The clearest example is to ask the question, for the hundreds (maybe even thousands) of people throughout history who has become giants from pituitary gland GH over-stimulation, did they also suffer from GH deficiency? From a anatomical point of view, radiologists looking at X-Rays and/or MRIs have shown that the pituitary gland have become enlarged, or has a unique tumor in the brain area. When it was found that this chemical called growth hormone was released mainly from the pituitary gland,  the link between cases of gigantism and the extra-stimulation and release of GH was clear.

The real question becomes, for a person to actually develop gigantism, is whether they have to suffer two different conditions simultaneously, 1) having growth hormone deficiency to make them more GH susceptible and 2) then have an overactive pituitary gland to develop into tall stature, or is it just an overactive pituitary gland?

I would guess the latter. Increased levels of GH that is coursing through the developing child’s system will make them bigger.

Now, the claims made are backed by studies, like the 2007 article “Growth Hormone Injections Add Height, But Kids Stay Short” In that article, it makes it seems like certain children are just destined to be short, and not even GH therapy would help them. The expensive, weekly injections would only give around 3 inches of extra height. The amount of money needed is stated to be around “Each half-inch in final height gained via human growth hormone therapy costs anywhere from $18,000 to $36,600“

Jackie Bryant, did make the point that even with with GH therapy, kids with idiopathic short stature would still be relatively short. However, we like to point out the word “relatively“. If Geoffrey took the time to look at the real data for the studies, he would see that technically the GH injections did make developing children taller, but maybe not as much as to change the fact that those children will not be the next Shaq.

We quote the article…

“Despite these findings, children treated with growth hormone remained short near the lower range of normal when compared to their peers.

“Genetic factors affect growth and final height, and parents should be realistic in their expectations about the potential effects of growth hormone,” Bryant said“

If a kid is only 4 feet tall and started to use GH on a weekly basis starting at 13, they are not going to be 6 feet tall by the time they are 18.

(Reference: Bryant J, Baxter L, Cave CB, Milne R. Recombinant growth hormone for idiopathic short stature in children and adolescents. Cochrane Database of Systematic Reviews 2007, Issue 3. Art. No.: CD004440. DOI: 10.1002/14651858.CD004440.pub2)

The other big problem with GH which we agree with is that to much GH can actually accelerate the bone age and bone maturity, so that the children will have fused growth plates earlier. Growth Plate Senescence does accelerate due to GH therapy usage.

However, that is the main thing. Arnold said that GH Therapy would not even work on children, unless they have GH deficiency. That is not exactly true. Even if a child is not GH deficient, they will get some level of height increase from the years of GH therapy when they are still growing, even though it may be just an extra 1 inch of height.

When it comes to the science of auxology, Geoffrey Arnold is not that well informed on the exact specifics. Please, for the future talk about the sociological, psychological, and anthropological aspects of height, short stature, and heightism, but stay away from the hard sciences, unless one has the right type of educational (or research) background to talk about such issues.

You would make mistakes informing the readers on the wrong things and pushing them in the wrong directions. If we made a mistake, we would be sure to let it be known and correct ourselves and change our opinions and positions on whatever matters we are discussing.

LSJL Update 8-7-14-How to Obtain a Hand X-ray?

Summary:

* LSJL increased right finger to be longer than the left.  Need X-ray to see if there are growth plates.  Easiest way to do this?

* LSJL increased left thumb over right thumb.  Thus LSJL can be reproduced.

* There are indications that LSJL is effective at increasing leg height.

* Clamping at the knee may be more effective than clamping at the ankle due to structural differences.

As you know, I’ve proven that due to LSJL my right index finger is now longer than my left.  The issue is that people are “So what?”  They don’t understand that the finger is made up of long bones(albeit with slightly different properties than the leg bones) and if you can induce length increase there it follows that you can increase bone length in the legs as well.

Originally, I ruled out getting an x-ray because people wouldn’t care about an increase in finger length but if I have successfully recreated a growth plate then that would successfully prove LSJL for the masses.  The problem is actually getting an x-ray of ideally both hands without having to get a doctors appointment first (and paying out of pocket for that).  I just want to go in, get an X-ray and then pick it up.  I can afford it for the $200ish I’ve seen especially since it’ll prove LSJL.  There’s a risk that there won’t be a growth plate but I am absolutely positive that my finger has grown longer by some mechanism and that it’s not due to bone thickening.  It is possible that it grew by some mechanism relating to articular cartilage endochondral ossification but people with osteoarthritis have endochondral ossification and I have not found any reports of bone lengthening.

So how can I get a hand X-ray with as little medical red tape as possible?  I want to walk in, get the x-ray, pay, and pick it up.

I’ve also been loading my left thumb and there’s a small but significant and noticeable difference between my left and right thumb.  I’m working on finding the best way to photograph it.  It does establish that the finger lengthening is not a fluke and is reproducible.

Another good sign is my legs.  My epiphysis has been changing in shape to become more hammerhead in appearance like my fingers dead.  Even if LSJL induces such “deformities” it would certainly be worth it to some people to grow taller.

And it seems as though my left leg is now longer than my right. The renewed growth can be explained by the following: I used to load my leg with a C-class clamp but now am using an Irwin Quick Grip to reduce slippage.  Now I am focusing much more on intensity of clamping but with shorter duration

(Note:  Since I cannot yet specify an ideal intensity I cannot guarantee against injury!).

Now I always used the Irwin Quick Grip on my ankle but didn’t really get good results there and haven’t seen a lot ankle changes despite clamping harder.  I think the reason for this could be that the knee is different structurally than the ankle and it makes LSJL more effective on that area.

So the reason why this routine could lengthen my left leg more than my right is that I load my left leg first as it is my weaker leg.  If I can get up to say a count of 130 on clamping my left leg(starting over at 0 if the clamp slips) then I clamp to 130 on my right leg.  So my left leg is guaranteed to get maximal clampage whereas the right leg is not.

Now there are other explanations as to why I feel my left leg has grown longer than my right:

1) Placebo effect.  I want my left leg to be longer to prove LSJL.  Although when I extend my legs my left leg is longer than my right and if I stand on my left leg I’m taller then if I stand on my right leg.

2)  Hip Rotation.  Which would explain the symptoms of the left leg extending longer without any actual lengthening.  But what would be the stimulus?

3)  My left leg has always been longer than my left.  I think I would’ve noticed it before.

So this effect isn’t perfect proof of LSJL but I think with the devolpment of more hammerhead-esque bones it is a good sign of LSJL’s effectiveness in increasing leg height.

——————–

Michael: One could go to Urgent Care, which is a type of walk-in facility which would let one get their bodies X-rayed. You’d still have to pay the costs though, but it would be faster. When I was looking at how deer antlers grow, I noted that the antlers where able to grow in length only because there was no physical constraint against the upper horn part from getting longer. Human legs have that constraint since we have to constantly be putting loadings on the feet from walking. if we could put our bodies into some bed for months on end while clamping, maybe there would be much bigger results. The effects on fingers, which are just jutted out and not being pushed down consistently on a flat surface would see much more noticeable effects.

Take This Easy To Obtain Supplement To Gain Lean Muscle, Stay Young Longer and Maybe Grow Taller

Take This Easy To Obtain Supplement To Gain Lean Muscle, Stay Young Longer and Maybe Grow Taller

For the longest time, the online community which are searching for way to grow taller have been orally consuming supplements of amino acid types for over a decade, ever since people started to get together and form discussion groups. I have never found any type of evidence to believe them on the amino acids, but a recent find has made me reconsider. On the Dr. Oz website, there was one article entitled “Natural Growth Hormone Boosters” which claimed that there are at least two things you can eat or take which is supposed to help increase the amount of HGH that is naturally produced and released into the body. They are…

  1. Fenugreek
  2. L-Arginine – Dosage: 2 grams, 3 times a day

There is a 3rd suggested idea which the Dr. Oz website mentioned, which is to use a Sleep Mask when sleeping. the reasoning is that when you wear a sleep mask, there will be less light that will reach your eyes, which will help with triggering melatonin for a much deeper, better, more restful sleep.

FenugreekFirst, let’s talk a little about Fenugreek. This compound is most often associated with increased milk production in new mothers who are breastfeeding. It seems that if the mothers consume fenugreek, they will produce more milk for the babies. You can google for the relationship between increased lactation and taking fenugreek. That issue, I won’t be going into. If I tried to really extend that thought process, maybe taking Fenugreek would be for the growth of the baby since the mother will be able to product more milk for consumption and maybe be able to breastfeed their baby for slightly longer.

There is also some anedoctal evidence that taking fenugreek is good for looking weight, can combat diabetes, increase estrogen levels, and even increase male libido levels. It is sold in bottles as a compounds which has similar effects to testosterone, but that doesn’t seem to be based on the real science. So that marketing is lying about that part.

It is the other supplement which I wanted to focus on, which has been talked about extensively before. L-Arginine. Apparently this amino acid when taken at about 6 grams a day does have some type of beneficial effect on HGH production and release. I am not a person who is always willing to accept medical physician’s suggestions at face value, but the fact that it was stated on the Dr. Oz’s website for increasing GH production does give it a little more credibility.

When I did only a slight Google Search on the connection between Arginine oral consumption with increased HGH production, I did find this study “Growth hormone, arginine and exercise.” The dosage there was 5-9 grams of Arginine.

What is really interesting here is that if you are at rest and take L-Arginine, the GH levels increase 2-fold, 2X. Compare it to exercise, and the increase would be maybe 4-5 fold. However, when you combine the amino acid with exercise, the GH production dropped to being just 3 fold. The conclusion in that article was that arginine might have some GH production inhibition effect when it is used in combination with exercise. Exercise alone seems to be much better than using it with this amino acid supplement.

I propose then that if an adolescent or teenager who is still growing should only take this supplement if they are too busy to have an active lifestyle where they are getting a lot of exercise. If they are already in some sports team and running around taking this supplement would do more harm than good in terms of increasing height.

What is probably the insane anecdotal story ever, in one thread on the BodyBuilding forum “Boosting HGH w/ L-Arginine & L-Glutamine” which referenced an article written by a guy named Jerry Emanuelson entitled “Arginine”

I clipped and pasted the sections of biggest interest below.

1 2 3

It is the last passage which is most interesting, as one girl supposedly grew 1 more inch in height at the age of 19 after taking 10 grams of the Arginine for a whole week. Of course, she became nauseous from the high dosage. Is this type of weak anecdotal stories based on real events, where people did grow taller? I don’t know, but there seems to be some unusual things going on.

New Chemicals and Cytokines For Physeal Chondrocyte Stimulation Discovered

New Chemicals and Cytokines For Physeal Chondrocyte Stimulation Discovered

In our most recent post on the possibility on using the chemical Parathyroid Hormone (PTH) to modulate and control the amount of growth that the vertebrate bones will go through in a developing adolescent, some new chemicals and cytokines were revealed to us which I had previously guessed has many stimulating effects on chondrocytes and the physeal layer.

The patent that we reference is entitled “Method of treating scoliosis using a biological implant (Patent #:US 8123787 B2)“. Under the section titled “Detailed Description of the Invention” the inventors write the following passage, which I clipped and pasted below. I will be going into detail to list and check the validity of the claims of each compound that they mention.

  1. Physeal Chondrocyte StimulationParathyroid Hormone (PTH)
  2. Fibroblast Growth Factors
  3. TGF-Beta
  4. FGF18
  5. FGFR3.

Out of all of these, it is probably the FGF18 that is the compound that I have found to be the most interesting, and that is mainly because I have never heard about this receptor or cytokine signalling factor before being associated with chondrocyte stimulation.

I remember that when it comes with FGFR3, inhibiting of that receptor is supposed to be able to treat children with achondroplasia like the chemical compounds NF449 and BMN-111 by BIomarin.

What I wanted to do is find at least 2 studies which validates the idea that FGF18 is beneficial on physeal activity.

I will not be focusing that much on the other cytokines but this compound FGF18 is the one which is most interesting to me. There has been maybe just 2-3 published papers on the efficacy of intra-articular injections of FGF18 to treat osteoarthritis is so the area and possibility of the growth factor/cytokine is still potentially huge.

I suspect that FGF18 when injected into the bone under the articular cartilage may cause cartilage repair.

Increasing Vertebral Bone Growth Using Minimally Invasive Intervertebral Disc Implants

Increasing Vertebral Bone Growth Using Minimally Invasive Intervertebral Disc Implants

Intervertebral Disc ImplantsThere has always been a lot of talk amount the online grow taller community where people would consider the idea of someone making the overall body bigger by somehow manipulating the vertebrate bones and/or the intervertebral discs. Almost all the talk have been focused on the discs, since the discs are not hard and difficult to remodel unlike the vertebrate bones. Discussions on disc decompression, traction machines, stem cell implants, and growth factor injections have been all been speculated before, but I recently found a new proposed idea which seems to make much more sense than all of them combined.

I agree that stem cell, scaffold, growth factor injections are all quite minimally invasive, so they are all somewhat good. This new idea is probably just as reasonable and attractive as any of the other ones I have suggested before in the past.

I refer the reader to the patent entitled “Method of treating scoliosis using a biological implant” (Patent # US 8123787 B) by Inventor James W. Ogilvie, Kenneth Ward, Lesa M. Nelson.

(The same idea is also available by the patent #s US20090105822,  US20110295369,  WO2009155159A2, WO2009155159A9.)

The method is for treating scoliosis, which is something most American Elementary School nurses check for to make sure children are growing properly and symmetrically but I wonder whether we can use the same type of minimally invasive slow release type of growth factor implants to increase the rate at which maybe adults can increase in their disc height.

From past articles I’ve read, it seems that scoliosis is something that mainly children who are still growing have. When one side of their vertebral growth plates become too active, their vertebrate column starts to become lopsided.

Vertebral Bone GrowthHowever, we do have the medical condition where adults suffer from scoliosis too. The last we checked on WedMD, there is no way to actually easily realign adult scoliosis. The most conservative treatment has been to make sure that the person with adult scoliosis does not suffer from great pain. Treatments has been almost always been for pain management. The other way is the drastic approach, which is to get surgery to correct for the curvature.

From the abstract of the patent we quote below…

“The present invention is a bone growth stimulating and promoting cytokine type biological implant preferably comprising PTH coated with a controlled release biodegradable coating that is implanted preferably in the concave side of a scoliotically curved spine in combination with a bone growth inhibiting type biological implant preferably comprising methotrexate or like anti-metabolite coated with a controlled release biodegradable coating that is implanted preferably in the convex side of a scoliotically curved spine. The insertion of the biological implant is highly non-invasion, especially as compared to more conventional spine surgical methods, and the biological implant does not decrease spinal mobility or spinal range of motion”

First, lets forget trying to use any type of bone growth inhibiting implant, but focus exclusively on getting the bone growth increasing cytokine to work. We are aware that Parathyroid Hormone aka PTH has bone growth beneficial effects.

From the other section in the patent….

“A method of treating a scoliotically curved spine in a patient being determined to be at risk of scoliosis curve progression comprising placing at least one of a growth stimulant, a medication, and a biological therapy on a concave side of said curve formed in said spine, wherein said biological therapy defines a dissolvable bone growth stimulant biological implant coated with a dissolvable coating, wherein determining said patient is at risk of scoliosis curve progression further defines a determination of genetic predisposition wherein DNA of said patient includes a plurality of genetic markers having an association with adolescent idiopathic scoliosis contained therein and wherein said risk is determined by performing logistic regression on said plurality of adolescent idiopathic scoliosis associated genetic markers“

So in the patent, there is more than just the growth stimulant added, but also a type of medication and the patient also should go through a type of biological therapy? Or does it mean that the dissolvable bone growth stimulant do all three parts?

While I am quite sure that this type of method to modulate vertebrate bone growth is going to be quite effective on developing children with functional growth plates, the big question to ask is whether this technique will work on adults.

First, after studying the diagrams and pictures of the structure and setup of the vertebrate bone column, we can say that there is a slight chance that the right type of cytokine might be better for making the discs more robust and tougher to compressive forces.

Now, we are fully aware that even in adults, there is still a very thin layer of hyaline cartilage, between the actual disc and the bone, which is really used as a connective tissue. It is just maybe 2-3 cells thick but it is there after the growth plates are gone. We wonder whether it is possible to get the PTH implants to dissolve slowly to get the few chondrocytes in the hyaline cartilage layer to proliferate and increase the thickness of the layer. If proliferation is possible, then we might be able to slowly, and I am talking very slowly, increase the height of the person with the embedded implants by millimeters over time.

However, like so many of our discoveries, the effects of this idea on young adolescent kids will always be much more effective and noticeable.