Monthly Archives: October 2013

Bmpr1a may be the key to form new growth plates

Bmpr1a is downregulated by aging in bone marrow.  LSJL upregulates Bmpr1b but expression of Bmpr1a is modulated by normal mechanical loadingBMP-2 interacts with Bmpr1a.  LSJL upregulates BMP-2.  Cells in the perichondrial groove express Bmpr1aPersistent upregulation of Hoxa2 which causes short stature downregulates Bmpr1a Bmpr1a is upregulated in a fractured tibia.  These facts are consistent with the observation that bmpr1a could play an on/off-switch in neo-growth plate formation.

BMP Receptor 1A Determines the Cell Fate of the Postnatal Growth Plate.

“Embryos deficient in Bmp receptor (Bmpr)1a or Bmpr1b in cartilage display subtle skeletal defects; however, double mutant embryos develop severe skeletal defects, suggesting a functional redundancy that is essential for early chondrogenesis. In this study, we examined the postnatal role of Bmpr1a in cartilage. In the Bmpr1a conditional knockout (cKO, a cross between Bmpr1a flox and aggrecan-CreER (T2) induced by a one-time-tamoxifen injection at birth and harvested at ages of 2, 4, 8 and 20 weeks), there was essentially no long bone growth with little expression of cartilage markers such as SOX9, IHH and glycoproteins. Unexpectedly, the null growth plate was replaced by bone-like tissues, supporting the notions that the progenitor cells in the growth plate, which normally form cartilage, can form other tissues such as bone and fibrous; and that BMPR1A determines the cell fate.

“During endochondral ossification, the progenitor cells committed act as the stem cells that replenish the pool of proliferative chondrocytes in the resting zone of the growth plate. The resulting daughter cells exit the cycle and undergo maturation via prehypertrophic, hypertrophic and terminal hypertrophic processes, followed by calcified cartilage formation. The vascular invasion then leads to the removal of cartilage, formation of bone marrow, and new bone formation and growth.”

“Is [there] a molecule that initiates and guides the progenitor cell in the resting zone of the growth plate, which solely differentiates chondrogenesis?”<-We want to find this molecule and induce it in adult bone.

” The failure of long bone growth indicates that there is no new progenitor cells added after deletions of Bmpr1a gene by one time injection of tamoxifen at newborn stage.”<-This is bad news that there may be a fixed pool of progenitor cells that is used up.  However, other stem cells could become progenitor cells after the right mechanical stimulus.

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“The work with a one-time injection of tamoxifen to remove Bmpr1a in cartilage at birth, which leads to a lack of long bone growth postnatally, raises the possibility that the progenitor cell number might already be present in the growth plate at birth with no more new progenitor cells added. This observation may explain why the rodent growth plate remains unfused during the animal’s lifetime but there is essentially no long bone lengthening after 28-30 weeks. In fact, in the 5-month-old control mouse, there is very limited cell proliferation in the growth plate compared to the early stage ”

So the goal in a bone lengthening program is to alter cell morphology of stem cells to be more like the progenitor cells present in the zone of ranvier and then to upregulate bmpr1a expression to encourage a chondrogenic fate.

This fixed pool of progenitor cells is also supported by s1p-ko mice which can form new growth plates from this pool of progenitors.

IGF-2 could play a role in priming MSCs to be more like the progenitor cells that form new growth platesIGF-2 has been used to induce longitudinal bone growth The LSJL scientists have also suggested that IGF-2 injections may be beneficial to LSJL lengtheningCTGF is linked to IGF2 and is another target to increase for supplements as well as HMGA2IGF2 is downregulated almost 1000-fold during senescence which further links IGF2 to the creation of progenitor cells.

I couldn’t find any supplements that increase IGF-2.  There’s a supplement called IGF-2 but that just seems to be the brand name.

Epigenetic consequences of a changing human diet.

“The ultimate methyl donor for epigenetic-methylation reactions is S-adenosylmethionine that is produced by the methylation cycle and it has been reported that periconceptional folic acid use alters the level of methylation within IGF2. A larger study of human pregnancy also observed an effect of folic acid use on IGF2 methylation in the offspring but the effect was restricted to folic acid use after 12 weeks gestation when women are not recommended to take the supplement. Late gestation use of folic acid was also associated with reduced LINE-1 methylation and altered paternally expressed gene 3 (PEG3) methylation. Three of the four significant associations with folic acid use and folate status were negative and one was positive, suggesting that it may be naive to assume that this is a simple substrate limitation effect or that the supply of nutrients involved in the methylation cycle will affect all genes equally.
Imprinting occurs before fertilisation but changes in imprinting methylation in animal models in response to nutritional exposures have been demonstrated into the early post-natal period for IGF2, after which the imprint is apparently fixed

Choline can result in hypermethylation of IGF2 in the liver.  Liver production of IGF2 is not stimulated by GH in adult mammals.  In adult mammals, IGF2 does not seem to respond to physiological status or vary with growth rate.

Expression of bone-related genes in bone marrow MSCs after cyclic mechanical strain: implications for distraction osteogenesis.

“In this study, a single period of cyclic mechanical stretch (0.5 Hz, 2,000 microepsilon) [for 40 minutes] was performed on rat bone marrow MSCs. Cellular proliferation and alkaline phosphatase (ALP) activity was examined. The mRNA expression of six bone-related genes (Ets-1, bFGF, IGF-II, TGF-beta, Cbfa1 and ALP) was detected using real-time quantitative RT-PCR.
The results showed that mechanical strain can promote MSCs proliferation, increase ALP activity, and up-regulate the expression of these genes. A significant increase in Ets-1 expression was detected immediately after mechanical stimulation, but Cbfa1 expression became elevated later. The temporal expression pattern of ALP coincided perfectly with Cbfa1.
The results of this study suggest that mechanical strain may act as a stimulator to induce differentiation of MSCs into osteoblasts{but could be chondrocytes with increase in bmpr1a levels}.”

This was the load applied to the cells during the study it’s reasonable to expect that the load is similar to that which is applied by LSJL.

“The transcription profiles of IGF-Ⅱand TGF-β were similar. Both genes reached maximum transcription immediately after mechanical strain and mRNA levels then decreased with time, except for a slight increase at 6 hours.”

The age of rats is not given and is vital information given that IGF2 is an age related gene.

It’s conceivable that LSJL modulates Bmpr1a expression given the study that shown it can be modified by mechanical loading and that LSJL modulates IGF2 expression given the study above that showed that it was upregulated by mechanical loading.

But still finding supplements that upregulate IGF2 and Bmpr1a would be exceptionally helpful.

Huge Breakthrough: New LSJL study with device

Development of a Portable Knee Rehabilitation Device That Uses Mechanical Loading

development of portable knee device<-Full study there

“Joint loading is a recently developed mechanical modality, which potentially provides a therapeutic regimen to activate bone formation and prevent degradation of joint tissues. Few joint loading devices are available for clinical or point-of-care applications. Using a voice-coil actuator, we developed an electromechanical loading system appropriate for human studies and preclinical trials that should prove both safe and effective. Two specific tasks for this loading system were development of loading conditions (magnitude and frequency) suitable for humans, and provision of a convenient and portable joint loading apparatus. Desktop devices have been previously designed to evaluate the effects of various loading conditions using small and large animals. However, a portable knee loading device is more desirable from a usability point of view. We present a device that is designed to be portable, providing a compact, user-friendly loader. The portable device was employed to evaluate its capabilities using a human knee model. The portable device was characterized for force-pulse width modulation duty cycle and loading frequency properties. The results demonstrate that the device is capable of producing the necessary magnitude of forces at appropriate frequencies to promote the stimulation of bone growth and which can be used in clinical studies for further evaluations.”

Note how the device looks like a table clamp:med_007_04_041007_f011.png

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“Dynamic loads applied laterally to the knee joint have been found to stimulate new bone formation not only in the distal femur and proximal tibia epiphyses, but along the entire length of each bone.”

“Knee loading is applied laterally to the epiphysis of the femur and tibia, which consist mostly of trabecular bone modeled to resist axial stresses{if the trabecular bone is modeled to resist axial strain than it is less resistant to lateral strain}. This allows greater deformations than are possible with similar loads in different loading modalities.  Dynamic deformations of the epiphysis cause alterations in fluid pressure in the intramedullary cavity, driving oscillatory fluid flow and molecular transport in the lacunocanalicular network in the bone matrix and in the medullary cavity”<-It is alterations in fluid pressure that could induce chondrogenic differentiation of the MSCs in the epiphysis forming new micro growth plates.

“The device applies cyclic loading of magnitudes up to 30N at frequencies ranging from 1 to 20 Hz and can cause small deformation in the knee.”

“The device proposed in this paper differs [from LIPUS and PEMF] in that it stimulates the bone tissue through direct mechanical loading at low frequencies.”

“A cyclic force applied on [the knee] would force a slight shift of the fluid within the bone towards the opposite end of the bone in a controlled fashion.”

“The device must provide sufficient force in a transverse load to the joint without being bulky or unbalanced.”<-This is a problem we may have too.  We might have to use a larger clamp for the knee.  The standard c-class clamp may work for smaller joints but a larger clamp may perform better for the knee.

“The force magnitudes that the device can produce must be at least 30 N”

“power generation units used in conjunction with a mechanism comprised of linkages was proposed as a means of shifting the power generation component into a position that allowed for better balance.”

“Operating the device at frequencies between 1 and 5 Hz is meant to simulate the therapeutic and rehabilitative effects of walking or running without the need to put the patient’s weight on the leg.”<-But would the effect be more significant than walking or running?  Walking and running have a lot of evidence showing that they don’t make you taller.

“the motor shaft is acting as the sliding block while the linkage connecting to the base plate serves as the crank. The rigid pivot arm that connects the motor shaft and crank before ultimately connecting with the pad at the top is the connecting arm.”<-much like a table clamp.

“Aluminum was chosen for the base plate, side plates, and the adjustable side as it is lightweight, but still provides the necessary strength. The pivot arm and lever arm were made of O1 steel. O1 steel has a high carbon content and a correspondingly high modulus of elasticity. This is crucial as these parts are subjected to higher stresses than are found in any other part of the device; it is important to minimize the deflection in these pieces since deflection of these parts would directly affect the range of displacement provided by the mechanism and may also contribute to damping{a decrease in the amplitude of an oscillation as a result of energy being drained from the system to overcome frictional or other resistive forces.}. High density polyethylene was selected for the pads as it allows a slight amount of deformation to increase comfort to the user while still being sufficiently rigid to transfer most of the force to the knee being loaded.”<-Could be helpful in designing a self-made LSJL device

“For the static loading, a 6.9 kPa pressure is evenly distributed across the 64.5 cm2 surface of both side of the pads directed outwards. A 44.5 N force is applied to the center of the motor shaft pushing away from the motor. This loading simulates the force applied by the motor and the reaction on the pads from the knee being loaded. “<-a lot of studies make it clear though that dynamic load is needed.

According to figure 11, Pressure generated is 6000Pa Or 0.006MPa.  Most figures show 0.1 to 10 MPA is what’s needed for chondroinduction but perhaps the pressure generated on the outside is not reflective of the pressure generated inside the bone which could be higher.

Here’s some force generated measurements:

LSJL device force

Here’s some displacement measurements:

displacement

“the force and corresponding displacement [of the artificial knee] over a period of five cycles at duty cycles of 50% and duty cycles of 100%. Such experiments when performed on an actual knee could be used to assist in the study of the force versus displacement of human tissue, a highly nonlinear reaction, as well as the effects of light mechanical loading to the bone tissue.”

The mechanics definition of displacement is the final position of a point (Rf) relative to its initial position (Ri).  Tissue displacement refers to the change in the form or position of the tissues as a result of pressure.  So the displacement of the artificial knee was about 2.5mm when the force generated was about 30N.  Since the displacement turns to normal it is referred to as an elastic deformation a plastic deformation would be a permanent change.  Thus the only way this device can induce new longitudinal bone growth is if it stimulates neo-endochondral ossification.

Here’s some information about the effects of tissue deformation on tissue deformation from a paper called Biomechanics of Tissues from the Journal of Rheumatology: “In a creep test, an instantaneous step or ramp load is applied to the tissue sample and held constant for an extended period of time. This is considered a load control test, and the resulting tissue displacement is measured. The displacement shows an initial elastic response of the tissue followed by a gradual increase of lengthening of the tissue. As the test proceeds, fluid is exuded from the tissue, and the solid components of the tissue are supporting the applied load. A “solid-like” material will be distracted to a point at which the solid components of the tissue will balance the applied load and will not elongate further. The modulus of the tissue is calculated as the stress of the tissue divided by the end displacement of the tissue. A “fluid-like” material will not be able to balance the applied load and will continue to elongate.“<-I don’t believe this occurred during my LSJL finger lengthening as the fingers increased in width greatly as well.

No mention of using the device for lengthening.  The basis of using LSJL on lengthening is based on studies that show that hydrostatic pressure can induce chondrogenic differentiation and that LSJL upregulates genes that do not only stimulate chondrogenesis of chondrogenitors but also of MSCs such as FGF-2, Gli3, and Cyr61 and of signs of mesenchymal condensation in LSJL images.  Also, in those images is apparent degradation of trabecular bone which would be permissive to neo-growth plate formation.

The condensed stem cells in the images are most consistent with granulocytes which are capable of chondrogenic differentiation.  According to Comparative study of the biological characteristics of mesenchymal stem cells from bone marrow and peripheral blood of rats., peripheral blood MSCs are more chondrogenic than bone marrow MSCs but chondrogenesis of bone marrow MSCs is not impossible.

This study does not provide more evidence that LSJL can increase length but it does support the notion that a table clamp is a perfect home made solution for performing LSJL.

Here’s a study with more about the effects of tissue deformation on the joint region:

The effects of manual therapy on connective tissue<-connective tissue therapy

“a low level of CT[connective tissue] damage must occur in order to produce permanent elongation. The collagen breakage will be followed by a classical cycle of tissue inflammation, repair, and remodeling”<-This paper doesn’t mention cartilage specifically but it mentions other tissues made of collagen fibers.

“Connective tissue that is loaded more quickly will behave more stiffly (will deform less) than
the same tissue that is loaded at a slower rate”

In figure 5, a graph is shown where it appears that microfailure of a tissue(the kind of stimulus that must occur in order to generate permanent lengthening of connective tisues) occurs 4-6mm(with a safer region being between 4-4.5mm) of displacement beyond which is complete failure of the tissue.  The displacement generated by the LSJL device is 2.5mm which is below this level to generate permanent lengthening of connective tissues.

p53 and it’s application to human limb regeneration

Michael has explored human limb regeneration for height increase in the past.

Retinoic Acid is mentioned as a key to human limb regeneration and p53 has been implicated as being modified by Retinoic Acid in a number of studies.  If we can find a protein link such as p53 that is important to limb regeneration and supplements to modify expression of that protein than perhaps we can use that information to grow taller.

In one instance, p53 activation due to Endoplasmic Reticulum stress resulted in dedifferentiation of hypertrophic chondrocytes into proliferative chondrocytesThe p53 pathway can be activated by a variety of oxidative and mechanical stresses.  Since activation of p53 is so common it’s unlikely that stimulating p53 is key to stimulating the processes of limb regeneration.  p53 activation is likely a necessary but not sufficient condition.

Regulation of p53 is critical for vertebrate limb regeneration.

“Extensive regeneration of the vertebrate body plan is found in salamander and fish species. In these organisms, regeneration takes place through reprogramming of differentiated cells, proliferation, and subsequent redifferentiation of adult tissues{so humans are likely missing one of these stages likely the reprogramming, can we induce this reprogramming with physical stimulus or supplements?}. Such plasticity is rarely found in adult mammalian tissues, and this has been proposed as the basis of their inability to regenerate complex structures.  Here, we analyzed the role of the tumor-suppressor p53 during salamander limb regeneration. The activity of p53 initially decreases and then returns to baseline. Its down-regulation is required for formation of the blastema, and its up-regulation is necessary for the redifferentiation phase{Since MAPK p38 activates p53, MAPK p38 levels may need to have similar trends as p53 levels during chondrogenic differentiation}. Importantly, we show that a decrease in the level of p53 activity is critical for cell cycle reentry of postmitotic, differentiated cells, whereas an increase is required for muscle differentiation. In addition, we have uncovered a potential mechanism for the regulation of p53 during limb regeneration, based on its competitive inhibition by ΔNp73. The regulation of p53 activity is a pivotal mechanism that controls the plasticity of the differentiated state during regeneration.”

To form a new growth plate you don’t necessarily have to form a blastema, thus reducing p53 levels may not be required.  Just inducing chondrogenic differentiation in MSCs may be enough.

“In salamanders, such as the newt and axolotl, limb regeneration depends on the formation of
a blastema, a mound of progenitor cells of restricted potential that arises after amputation. Following a period of proliferation, blastema cells redifferentiate and restore the structures of the limb.”

“Upon amputation, muscle, cartilage, and connective tissue cells underneath the injury site lose their differentiated characteristics and reenter the cell cycle to give rise to the blastema”

“inhibiting p53 disrupts limb regrowth in salamanders”

“a decrease in the expression levels of Gadd45 and Mdm2 between the early (9 d postamputation, dpa) and late (18 dpa) bud stages, corresponding to the period of blastema formation, followed by a return to the initial levels upon redifferentiation”

“α-pifithrin [is] a p53 inhibitor and nutlin3a [is] a p53 stabilizer, which disrupts the p53–Mdm2 interaction”

“Stabilization of the p53 level at the time of blastema formation, when it normally decreases, led to an impairment of the regeneration process”

“[There exists] upper and lower thresholds of p53 activity, above or below which blastema formation is impaired.”

“the overexpression of the p53 dominant-negative construct DDp53, from the mid-bud stage onwards, resulted in delayed and defective regeneration”<-But not completely absent which means that if a way to inhibit p53 is not found it does not mean completely inhibited regeneration.

“[UV light results] in p53 stabilization and up-regulation of Gadd45 [in both humans and salamanders]”

P53 levels are self reduced because p53 produces MDM2 which degrades p53.  Unless there is oxidative or mechanical stress, p53 levels tend to degrade.  Perhaps this is why spontaneous chondrogenic differentiation can occur in microgravity where there are no oxidative and mechanical stresses?

People With Acromegaly Due To Excess GH Have Thicker Than Average Articular Cartilage

People With Acromegaly Due To Excess GH Have Thicker Than Average Articular Cartilage

Something which was suspected by me after reading a few interesting studies on Articular cartilage and acromegaly made me hypothesis that if a person has acromegalic symptoms due to excess GH production, they would probably have thicker than average articular cartilage at the end of their bones.

Based on the study “Reversibility of Joint Thickening in Acromegalic Patients: An Ultrasonography Study” my guess is validated to some extent. There is a 2nd study entitled “THE ARTICULAR AND OTHER LIMB CHANGES IN ACROMEGALY” which I was not able to get to, but I would guess at this point would provide more proof that this hypothesis is valid.

However, the obvious question to ask is “how does this scientific fact contribute towards the research or finding a way to make me taller?

I am not exactly sure at this moment. I am currently having a little bit of trouble in making the connections between the research on how articular cartilage growth works and height increase techniques and possibilities. I can always hope that if we figured out that if we can conclude that the articular cartilage still is going through processes of remodeling and ‘growing’ in some way it might mean that we can stimulate it using some type of growth factor or collagen to make it accelerate the rate of cartilage growth, leading to longer bones. If it is true that the articular cartilage at the ends of bones have the ability to go through hypertrophy from excess of GH running through the system, maybe it might be possible to using the increase in volume of the cartilage for some end goals.

From the 1st study…

“The thicknesses of shoulder, wrists and knees articular cartilages and that of heel tendons were significantly increased in patients with active acromegaly compared to those in healthy subjects”

These test subjects were assumed to have no other type of bone problems at their adult age except for the acromegaly. When the subjects were given 6 weeks of treatment using something known as octreotide (OCT), the thickness of the articular cartilage actually shrank. I would later learn that octreotide is a type of synthetic somatostatin which has a very strong ability in inhibiting growth hormone and insulin stimulation.

If a synthetic somatostatin and growth hormone increases have a way of regulating the thickness of cartilage in our articular cartilage, it could explain why a few people who did take growth hormone injections as an adult increased their height by around 1/4-1/2 of an inch. The increase in height might even be semi-permanent, unless there was a 2nd physiological process going on in their body inhibiting the growth hormone release.

So this could be a new way of increasing our height as adults, but the gains could be as little as 1/4th of an inch in height but the other effects is that our wrists, ankles, and joints become wider and thicker.

Articular Cartilage At The End Of Epiphysis Do Growth Thicker Making Bones Longer (Big Breakthrough)

Articular Cartilage At The End Of Epiphysis Do Growth Thicker Making Bones Longer

I realize that these days I post so little but when I find something very interesting I still make a really good post. This news might really give you guys so really good hope!

TextbookSo recently I stopped by a large bookstore in the Gangnam area of Seoul. I had casually mentioned to my girlfriend that I do a lot of medical research and flirted with the idea of maybe one day going to medical school, just for the experience of challenging my intellect. She seemed to be very attracted to the idea of her potential future husband possibly being a doctor and really nudged me towards getting a book that all medical students read, which is a standard anatomy & physiology book. So I scoured the bookshelves looking for something reasonably priced and picked up the a University Level Biology Book “Seeley’s Anatomy & Physiology, 9th Ed. (International Student Edition)“. You can see my iphone picture of it to the right.

I decided to peruse through the book to see what they had to say about the epiphyseal growth plate cartilage and how the bones in the body grow. I am already very familiar with how the long bones go through periosteal bone growth, appositional growth, longitudinal growth, and endochondral ossification. However there was a very interesting section which really jumped out at me. On page 186 of the textbook, right underneath a diagram showing the standard defined zones of the epiphyseal plate, there was just 1 paragraph dedicated to the fact that the articular cartilages at the end of bones, long and short, seem to contribute to the volumetric size of the bone!

I took the liberty to take a picture of the section and pasted it below…

Articular Cartilage Growth


I am not sure whether the reader can read what the section says but here are the main points on the paragraph…

1. The epiphysis does increase in volumetric size from growth of the articular cartilage.

2. Articular cartilage increase the size of bones without even an epiphysis

3. How the articular cartilage makes the bones around it grow in size is similar to how longitudinal growth in the normal growth plates are done.

4. It seems that the chondrocyte columns that is easily seen in any histological examination of the epiphyseal growth plates also exists in the articular cartilage, but they are not as ‘obvious’, whatever that means.

5. It seems that the chondrocytes which are on the surface of the articular cartilage is just like the mesenchymal stem cells which are the progenitor cells which differentiate into the chondrogenic lineage found in the resting zone of the growth plates.

6. When the epiphysis reaches what is supposed to be a maximum size (whatever that may be), the articular cartilage seems to stop its appositional-like growth.

What this proves is that apparently the articular cartilage does contribute to the length of long bones by making the ends of the long bones, the epiphysis larger in size!

They do this just like growth plates.

So the obvious questions to ask then is…

1. Why does the epiphyseal cartilage disappear while the articular cartilage stays for life?

2. Why does the articular cartilage stop producing more bone underneath it after a certain age?

3. Shouldn’t the articular cartilage still have some bit of chondrocytes in it in column-like alignment which could possibly start to hypertrophize and make the bones slightly (1-2 mm) longer?

Answer to Question #1: We answered the first question in an older post Why Does The Epiphyseal Cartilage Disappear But The Articular Cartilage Remain? (Breakthrough!). The answer is that articular cartilage has the SOX9 gene activation the SOX9 Protein and the presence of the Chondromodulin Type 1.

Deer Antler TipAnswer to Question #2: I am going to propose a very good guess on this. When I wrote the post on the analysis of deer antlers Increase Height And Grow Taller From Deer Antler Regeneration Principles, and how they grow biannually, we saw that the structure at the very tip of the deer antler had a mesenchyme reservoir. This is what I would guess the articular cartilage sort of has. The human body has a limited number of mesenchyme close to the surface of the articular cartilage which will slowly over time differentiate into chondroblasts, and then into chondrocytes, and sort of align themselves in some type of columnar fashion.

When the human being reaches past a certain age, the mesenchyme reservoir gets completely used up. There is nothing left.

Answer to Question #3: I think that there is not enough chondrocytes or mesenchyme left on the inner size of the articular cartilage surface. There might be a few, and there might be ways to get the chondrocytes to hypertrophize, but there is just not enough and there is no way to get the few left to organize themselves in column fashion.

Conclusion:

This new discovery is very, VERY Promising. If the articular cartilage, which is supposed to always exist throughout life, except for maybe certain arthritic cases, does make any type of contribution towards the overall length of long bones, then we have many tools (growth factors like BMP-7 and chondrocyte aligning and regulation signalling factors like thyroxine) already to possibly alter it in certain minimally invasive approaches to get it to start to thicken again and get chondrocytes to multiple in the cartilage.

If we can make the surface of the articular cartilage get some extra mesenchyme, which I theorize is how it originally contributes to the overall size of the epiphysis, then it will start to thicken again, and the chondrocytes on the surface will slowly seep down by diffusion through the cartilage extracellular matrix of Glygoaminoglycans, Proteoglycans, and Collagen Type II, until they form columns. Eventually the diffusion rate of the chondrocytes will slow down, and the chondrocytes will start to form into column-like shapes. I imagine it like how rain water droplets fall slowly into molasses, and the droplets eventually go back into the spherical form due to maximization of the strength of the Force of the Surface Tension. The rain droplets gets trapped at some level, and the result are rain droplets/ chondrocytes stacking along top of each other…

Articular Cartilage LocationJust look at the picture I took from page 189 of the same textbook. See how the shape and location of the articular cartilage is almost flat and looks very much like half of a full growth plate. It does not enclose around half of the entire epiphysis like it is drawn in some medical school anatomy textbooks. It just sits on the top of the bone. And this is for an adult bone!

So all that we have to do to get the articular cartilage to start to deposit bone tissue on the cortical bone layer below it is to get more mesenchyme above it! Of course the obvious joint we are talking about is the knee joint, which is a synovial joint.

The knee synovial joint is mainly filled with types of compounds, hyaluronan, and aggrecan, with some Collagen added in. We know that taking supplements of Glucosamine Sulfate around 1500 mg does seem to make the knees feel better.

TGlucosamine Grow Tallerhe cheapest way to possibly grease up the surface of the articular cartilage would be to take those glucosamin sulfate at 1500 mg twice a day, for upwards of 3 months. The added collagenous material could possibly cause the cartilage to get slightly thicker. From This Link Here, a guy named Greg Bailey from Australia back in Sept 2010 stated that he grew from 5′ 10″ all of his adult life to almost 6 feet tall in his 50s from taking Glucosamine. See the picture to the right…

This is not the only case where ingesting Glucosamine Sulphate seemed to make people grow taller. There is a very famous article written by a person named Jennifer Hope (Hope???) entitled “Can a pill make you taller in four weeks?” which also stated that taking Glucosamine Sulfate at 1500 mg daily for around 1 month will make you around 2-4 mm taller.

Buy the Glucosamine Sulfate at 750 mg from Amazon here! (240 Tablets)

Glucosamine Sulfate 750 mgPrice: $22

Directions: Take 2 of the tablets, which combine for a total of 3000 mg of Glucosamine Sulfate every day, 1 during the morning and 1 during the evening.

I am part of the Amazon Affiliate program so if you buy it from the link above I do get a small bit of commission earnings. (which is around $1 for each bottle you buy)

Or you can buy the Glucosamine Sulfate at 1500 mg and just take 1 pill a day…

Buy the Glucosamine Sulfate at 1500 mg from Amazon here! (450 Tablets)

Glucosamine Sulfate 1500 mgPrice: $39 w/ Free Shipping

So if the ingestion of the Glucosamine is something one does not want to try, there is something slightly more invasive which I propose at this point which probably has a high chance of getting through.

However a much more effective way is to get a syringe and use the StemPro® Chondrogenesis Differentiation Kit sold by Life Technologies. You want to combine the StemPro Chondrogenesis Differentiation Kit with the BMP-7 sold by Life Technologies as well. In my previous posts comparing the dozens of current growth factors out there which are most effective in getting the progenitor cells to differentiate into the chondrogenic line, BMP-7 aka OP-1 is the most chondrogenic, compared to say BMP-2, BMP-6, or BMP-9.

You want to get the angle just right to get the initial syringe just along the surface of the middle of the articular cartilage of the proximal tibial epiphysis. The first injection will be the right mesenchyme, the MSCs, and the 2nd injection, using the same needle as a vessel would be the administration of the BMP-7, to get the progenitor cells to differentiate into the chondrocytes, which will over time diffuse downwards the articular cartilage into columns. To activate the chondrocytes to hypertrophize, you can use the various methods of chondrocyte hypertrophy that Tyler has talked about over the years, which range in a variety of subjects.

Note: If you take the 2nd approach, it might be slightly hard to obtain these tissue engineering lab components. That will be the 1st major hurdle since this type of material seems to be available only for medical professionals, physicians and researchers. Of course, I am aware that there is at least 1 person who regularly reads this blog who just finished their medical school and was doing their first year residency.

Note #2: You want to also get a biopsy of your cartilage tissue and issue how your own immune system it will react to the injected MSCs and BMP-7. BMP-7 which is just a growth factor by itself should be the same in all humans so the human body’s immune system should not react when it gets injected, but the MSCs might be. When doing an ear or nose piercing for a new stud or earring, it might be smart to save the fibrocartilage material and test how the cartilage tissue in calf serum medium would react with the MSCs injected into it. It is also suggest that a 2nd biopsy is done with some extracted blood and have a histological examination to see how your bodies immune system will react to the injected MSCs. Will it start to go into inflammation, White T-Cells attacking it, Red Platelets clogging around it, or maybe nothing at all?

So to do the 2nd part, for safety reasons, you will be required to do an immunological testing to see whether the MSCs you did get will be okay with the overall system. I would guess that if one did manage to get the cells and the growth factors on the top of the articular cartilage, the result would be upwards of just 1 cm in increased height, if there is adequate induced chondrocytes and the right technique for chondrocyte hypertrophy is chosen.

Tyler’s Notes:

It has been established that longitudinal bone growth occurs at the articular cartilage of some bones as shown by some finger studies.  However, the joint and epiphysis may constrain this growth.  Possibly related to the periosteum.  Endochondral ossification has been shown to occur at many joint areas.

Longitudinal bone growth is not significant in the articular cartilage due to some constraint from the epiphysis or the joint.  There have been studies showing that the periosteum constrains growth and that periosteal stripping can enhance growth.  Since LSJL is applied on the joint cavity it could influence the mechanisms by which the joint cavity and epiphysis constrain growth.  However, LSJL seemed to upregulate periosteal related genes.  But none of the genes were periosteum specific so it could’ve just been a correlational effect.  And the afformentioned study, compared the perichondrium to the periosteum rather than the periosteum to the bone.  If the perichondrium does not constrain growth whereas the periosteum does it’s possible that the LSJL could enhance growth by altering the shape of the periosteum so it is not so growth constraining.  LSJL did upregulate perichondrium genes much more than periosteum genes.

I’d like to also mention a note from the study “Metacarpophalangeal length changes in humans during adulthood: A longitudinal study” which states “When cartilage thickness exceeds the critical dimensions that limit nutrition by diffusion, the cartilage cells hypertrophy and degenerate, the spaces become vascularized, and osteoblasts develop to initiate endochondral bone formation in the midst of the articular cartilage.”<-So a primary way to induce endochondral ossification is to just increase articular cartilage thickness.

Conclusion:

1. Articular cartilage undergoes endochondral ossification.

2. This endochondral ossification results in longitudinal bone growth in bones that do not have joints or epiphysis such as the bones in the fingers.

3. Identifying what in the joint or epiphysis constrains growth and how to disrupt this may allow articular cartilage to generate longitudinal bone growth in long bones with a joint and epiphysis.  Although as shown in the finger studies, growth via articular cartilage is very slow.

What Happens When A Tall Person Stops Being The Tallest Person?

This is a post to maybe probe slightly into the psyche of people who might already be tall.

I was watching this YouTube video on Kungfu Panda and this episode seems to suggest just what might happen when people who was considered big or tall stop being tall because other people around them started to grow and become bigger. I am not sure how many people watched the movie but apparently one of the characters, being of very small size used some magical potion which they drank to make themselves much bigger in size.

When the antagonists realized how this previously small character managed to grow so much bigger, they wanted to be even bigger. As for the previously largest character, some crocodile, he became angry, and possibly a little jealous, that he was no longer the largest of them all. He enjoyed the fact that he was the largest of all the animals, and when there was a bigger animal that showed up, he felt threatened from comparing their sizes.

What would happen is that he would steal the vial of magical growth potion and drink all of it himself, when all you needed to do was take a couple of sips to get the size you want. It seems that this super-sized crocodile had a sort of complex over his size. He wanted to distinguish himself using his innate size. No one can be bigger than him.

It is a nice episode. You should watch it.

I am reminded of the fact that there apparently was a poster on some forum (forgot which one) who was 6′ 4″, which would be considered big, but desired to become 7′ 0″. It was some male teenager probably still in High School.

It seemed that they decided to place a large part of their identity on their size. How they defined themselves had a huge part over the fact that this person was either the tallest or one of the tallest in their class.

They derived a lot of self worth and self-esteem from being among the biggest in their class, school, or group of friends. They recently noticed that their friends are starting to grow taller, and started to catch up to them in height while for them, they seemed to have stopped getting taller. It seems that this person desired to always be a ‘stand out’ from their group of friends or class by wanting to push past their social circle.

They wanted to push past their friends and peers in terms of height so that the other people can never catch up to them at least on the issue of size. As long as this person could be 7 feet tall, no matter what happens, they can always feel good about themselves for being the tallest among their group.

The late writer Michael Crichton tells a similar story. At around 6′ 9′ – 6′ 10″ he was almost always the tallest person in any room, and often by a large measure. Being maybe even 6′ 10″ at some point in his life, he is around 4 standard of deviations away from what the average height of men are supposed to be. He tells the story of how he met Wilt Chamberlain the first time. It was said that Crichton was so shaken-up by the experience of finally meeting someone so much taller than him that he actually had a small identity crisis.

From the website MusingsOnMichaelCrichton

As an adult, Crichton found being tall made it difficult to hear people speaking to him if he was standing. (New York Times) But meeting Wilt Chamberlain, who at 7’2” topped Crichton by five inches, gave him a different perspective. 

“To my surprise, I found myself standing on a step to make myself taller….I was so uncomfortable that, after a half-hour, I had to leave. When my therapist asked me why I wasn’t happy not to be the tallest, weirdest person in the room, I had to admit that a part of me is proud of what makes me different.” (Los Angeles Times)

When you have been lauded, admired, praised, and respected throughout your entire life for something that is so fundamental, and so immovable as extremely tall height, it is hard separate one’s sense of self-worth and self-esteem from one’s size. What happens on the day when you finally do come face to face with someone who is clearly taller than you?

Does the fact that the person in front of you mean that they are inherent better than you, and there is nothing that you can do about it?

Since human height is supposed to be something we can’t change, no matter what we do, it does seem to give people who are taller a sort of smug, internal satisfaction, in sort of realizing at some level that they will always have something over another person, no matter what the other person does.

I sort of get it. A significant portion of people who are extremely tall probably has some type of complex over being the tallest person or the need always be the tallest. So what will happen when they meet someone who is bigger than them?