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Can Flexioss be used to to prove LSJL or Lateral Impact Loading?

Arthur Lazar is someone who has spoken about LSJL in the past on Quora. “Not really. There is 0 evidence for that. The original working experiment was performed on mice – mice growth plates never ossify. MAYBE if someone would develop a machine which can put perfect constant pressure, perfectly shaped for bone area where the pressure is supposed to be, then in theory it could work. But this is a bro-science, so it’s a big MAYBE. But as for now, using clamp, dumbelss or whatever you can use to press at bone would never work.”<-Mice growth plates don’t ossify but they become senescent which is just as bad for growth.

Here’s some more of his thoughts on LSJL: “Yes, I do work on a device for automatic long bone loading method as I believe that the standard lsjl loading (manual with clamps, weights, mpistols) is an invalid approach that lacks consistency, frequency and stability which all was provided with the original, successful experiment.”<-I don’t know what an mpistol is. I believe it is a typo. I don’t know what the original intent is.

“Thank you for your interest, but currently my team is complete and current priority of the projects puts the lsjl idea on the bottom of the list. When I am done with the prototype and IF it will have a desired affect on Flexioss structure (in the terms of force application on the structure) I will publish the design in order to expand the team and get potential investors interested.”

Here’s another set of communications someone had with him.

So the question is should we be using flexioss to try to find the best loading regime to induce the proper stimulation to induce new longitudinal bone growth. I believe personally that the best regime is some kind of lateral impact loading(I believe that tapping the epiphysis would be superior than the diaphysis now but I am trying both). Clamping has a slippage problem which impact does not have. The loads of direct lateral impact are stronger than that occur during normal physiological activities which are more axial.

Lateral impact does occur during boxing both to the hand and to the face and ribcage. Also, it occurs to the feet bones during running(but this depends on whether you are a heel or toe striker). It also happens to bones during muay thai kick boxing.

The problem is that this impact is often at irregular intervals and not targeted to specific areas of the bone such as the epiphysis. The epiphysis is where there is less cortical bone, is close to where the growth plates used to reside in skeletally mature individuals, and is close to the articular cartilage which if stimulated could potentially contribute to height growth. In muay thai you have no control over where you are kicked and if you do kick you are trying to use the strongest part of the bone.

Lateral impact has the potential in my opinion to drive the most fluid forces throughout the bone. Greater than any axial impact certainly due to the pressure gradient of the bone and the epiphysis is the weakest most porous part of the bone so impact to that area has the potential to drive fluid forces throughout the entire bone. Muscular contractions also have the ability to stimulate fluid forces throughout the bone but that is limited by muscular size and strength. Lateral impact also has the ability to gradually induce plastic deformation throughout the bone. Most plastic deformation occurs axially to shorten the bones such as in rickets/paget’s disease etc. Lateral impact loads have the potential to induce plastic deformation in a way such as to lengthen the bones.

Here is the flexioss.

So the question is can we use the flexioss to find the best way to induce lateral plastic deformation in such a way as to lengthen the bones or to induce fluid forces to either induce articular cartilage endochondral ossification or to cause denovo cartilagenous regions within the bone.

In the study Dose-dependent new bone formation by extracorporeal shock wave application on the intact femur of rabbits., they found trabecular bones heaving with cartilagenous tissue which would be huge as bone tissue is not capable of interstitial bone growth.

The manufacturers of flexioss claim that it has properties similar to that of cancellous bone so yes it can potentially be used to find the best loading regime to induce plastic deformation in such a way as to longitudinally lengthen the bone. Obviously, it can’t really be used to mimic the fluid properties of the bone.

McKenzie Chin Tuck a fast and easy trick to be taller

I have tried the McKenzie Chin Tuck posture and it absolutely makes you measure taller but your eye level appears shorter. It is not a breakthrough by any means but I have tried and you can see yourself becoming taller in the mirror when you do it.

So when you adopt this posture you measure taller because you are maximizing the apex bump of your head. But personally, I feel shorter because with a more backwards head posture my eyes are at a higher level so people are shorter relative to high level.

There is an exercise related to this where you push the chin back to get a neck muscle stretch and there are some indications that it may be worthwhile to do this.

I write more in my response to Body Height changes with hyperextension. Basically temporary hyperextension of the spine(15s) can result in temporary height gain due to disc hydration. And I think this exercise may achieve hyperextension of disc components. So I’d say it’s worth doing but only brief periods as you would be better suited to strengthening your neck muscles via something like free weight training or machines if you can’t do free weights due to injury or a structural reason.

It’s mentioned further in the body height changes with hyperextension study that it’s putting the load on the facets that enables for disc hydration. You’d think that tilting your head back would actually put the load on the facets. But I think the key is that tucking your chin in achieves neck muscle activation and if you look at the back muscle anatomy if the muscles are activated they will pull everything upwards.

Note that the majority of the back muscles slope upwards so when they are contracted they indirectly pull up the spine in alignment. I write about the muscular pull maximizing height gain here.

So I’d say in general adopt the mckenzie chin tuck along with chest up/shoulders back to maximize back muscle activation in posture. And occasionally do the press the finger against the chin thing for short periods of time to allow for disc hydration.

The drawback for the mckenzie chin tuck posture is that although it makes you measure taller it makes your jaw look smaller.

Here’s a video that explains it more:

I find that just bringing your chin is enough to get a good height gain appearance without having to worry about protecting the technique yes as mentioned you will have double chins but you will measure taller.

This guy looks taller after doing the McKenzie chin tuck:

Here’s a study that backs up the McKenzie chin tuck:

Head posture and loading of the cervical spine

” Precision stadiometer tests were run, using seven subjects, to measure the effects on spinal length of different angles of gaze. After 1 h exposure whilst sitting in a controlled posture, there were significant differences in the shrinkage of the spine between the horizontal gaze and the 20° and 40° angles below the horizontal. The increased spinal loading demonstrated by the increase in spinal shrinkage calls into question the recommendations for angle of gaze recommended in textbooks.”

I think it is the forward posture affecting the height change and not actually the gaze of the eyes.

“The mean compressive load on the cervical discs was 10 kg higher for the forward flexed position”

“Each subject would attend on three separate days, on each of which one of the three
randomly chosen head angles, 0 degree, 20 degrees and 40 degrees, would be tested.”

“A shrinkage of the spine during the forward inclination of the head, observed during this
experiment, of approximately 1 mm over a 1 h period, equivalent to about 5% of the total diurnal shrinkage”

Is LPP(Link Protein N-terminal peptide) a potential height increasing supplement?

I went through the papers to see if there’s any potential. LPP is linked to HMGA2 which does have height increase potential applications.

Link Protein N-Terminal Peptide as a Potential Stimulating Factor for Stem Cell-Based Cartilage Regeneration

<-the title right off the bat suggests potential as anything that suggests cartilage regeneration may be able to increase height if even only in the joints or spinal height.

“Link protein N-terminal peptide (LPP) in extracellular matrix (ECM) of cartilage could induce synthesis of proteoglycans and collagen type II in cartilaginous cells{if the extracellular matrix of the joints or intervertebral discs is thicker that would overall make you taller!}. Cartilage stem/progenitor cells (CSPCs), the endogenous stem cells in cartilage, are important in cartilage degeneration and regeneration. We hypothesized that LPP could be a stimulator for stem cell-based cartilage regeneration by affecting biological behaviors of CSPC. CSPCs were isolated from rat knee cartilage. We evaluated the promoting effect of LPP on proliferation, migration, and chondrogenic differentiation of CSPCs. The chondrogenic differentiation-related genes and proteins were quantitated. Three-dimensional culture of CSPC was conducted in the presence of TGF-β3 or LPP, and the harvested pellets were analyzed to assess the function of LPP on cartilage regeneration. LPP stimulated the proliferation of CSPC and accelerated the site-directional migration. Higher expression of SOX9, collagen II, and aggrecan were demonstrated in CSPCs treated with LPP. The pellets treated with LPP showed more distinct characteristics of chondroid differentiation than those with TGF-β3. LPP showed application prospect in cartilage regeneration medicine by stimulating proliferation, migration, and chondrogenic differentiation of cartilage stem/progenitor cells.”

So there is a possibility of LPP injects in cartilage regions to make people slightly taller of course with caveats as not everything that has potential works. In the paper there’s a lot about degeneration of articular cartilage so they so the potential for application in that area which would in turn result in potential height increase.

“Link protein, a glycoprotein that exists in human intervertebral discs as well as in the articular cartilage, plays an important role in strengthening the binding between aggrecan and hyaluronan. Link protein N-terminal peptide (LPP) is the cleaved N-terminal 16 amino peptide (DHLSDNYTLDHDRAIH) of link protein. LPP was thought to be the functional fragment of link protein as the cross-linker”

If you look at the doses figure 5 there seems to be an equilibrium effect with around 50ng/mL having the equilibrium effect.

This suggests that if you are not deficient in LPP it may have no impact on height whatsoever(LPP already exists in cartilage regions).

So LPP may have no impact on articular cartilage regions(but that doesn’t mean that it wouldn’t) but there is still the possibility of using LPP to induce stem cell differentiation into chondrocytes. But I don’t think the differentiation of stem cells into chondrocytes is the problem. In distraction osteogenesis there is already chondrogenic differentiation. The problem is likely a lack of stem cells in general in the articular and that bone is not capable of interstitial growth. Perhaps LPP could be used as part of microfracture surgery whose goal is to create microfractures to get stem cells to the articular cartilage but the problem is that the cartilage formed is fibrocartilage. So perhaps LPP could be used to make the cartilage purer.

Bone usually heals by bone remodeling perhaps LPP injections could encourage it to heal via endochondral ossification resulting in taller height over time?

Simultaneous Recruitment of Stem Cells and Chondrocytes Induced by a Functionalized Self-Assembling Peptide Hydrogel Improves Endogenous Cartilage Regeneration

“The goal of treating articular cartilage (AC) injury is to regenerate cartilage tissue and to integrate the neo-cartilage with surrounding host cartilage. However, most current studies tend to focus on engineering cartilage; interface integration has been somewhat neglected. An endogenous regenerative strategy that simultaneously increases the recruitment of bone marrow mesenchymal stem cells (BMSCs) and chondrocytes may improve interface integration and cartilage regeneration. In this study, a novel functionalized self-assembling peptide hydrogel (KLD-12/KLD-12-LPP, KLPP) containing link protein N-peptide (LPP) was designed to optimize cartilage repair. KLPP hydrogel was characterized using transmission electron microscopy (TEM) and rheometry. KLPP hydrogel shared a similar microstructure to KLD-12 hydrogel which possesses a nanostructure with a fiber diameter of 25–35 nm. In vitro experiments showed that KLPP hydrogel had little cytotoxicity, and significantly induced chondrocyte migration and increased BMSC migration compared to KLD-12 hydrogel. In vivo results showed that defects treated with KLPP hydrogel had higher overall International Cartilage Repair Society (ICRS) scores, Safranin-O staining scores and cumulative histology scores than untreated defects or defects treated with KLD-12 hydrogel, although defects treated with KLD-12 and KLPP hydrogels received similar type II collagen immunostaining scores. All these findings indicated that the simple injectable functionalized self-assembling peptide hydrogel KLPP facilitated simultaneous recruitment of endogenous chondrocytes and BMSCs to promote interface integration and improve cartilage regeneration, holding great potential as a one-step surgery strategy for endogenous cartilage repair.”

“LPP can induce directional migration of nucleus pulposus cells (NPCs) and cartilage-derived stem cells (CSCs)”

Now is this cartilage “taller” than before the injection? I can’t really tell from the images. IF you look at slide F it looks there might be some slight overgrowth.

Overall I’d say use LPP does have some height increase potential but probably very minor and it’s probably going to be a while before it can be used for height in practice.

Can Regeltec Hydrafil injections make you taller in the spine?

The short answer is yes of course. Loss of spinal height is loss of height. There was a limb lengthening surgery for the spine but it was only for immature pigs. And the growth achieved was very small. There is a growing rods technique for scoliosis patients but the lengthening achieved according to Spinal Lengthening With Magnetically Controlled Growing Rods is something on the order of millimeters. But that adds up.

The intervertebral discs are a component of height. Some people have claimed on forums to get taller in the spine via stretching and I would love to see those claims validated in some way.

Here’s the regeltec website.

Here’s a video with more about the technique:

There was a clinical trial but no results have been posted. I could find some data that the Hydrafil reduced backpain but no data on the impact on height. Of course how much height is added would vary on how much the disc is degenerated. And it would be interesting if you could somehow overfill the disc in order to add height above capacity.

There’s definitely a cost issue as there’s a lot of discs to inject hydrafil into. But there’s no surgery and you just have to inject it that should alleviate the cost. So it may not break the bank but it would probably be a significant sum like all surgical procedures.

But it may be a good non-invasive way to add a little bit of height?

LSJL studies 5: LSJL device design

This paper discusses a lateral bone loading device. It mentions a capacity of 40N which I think won’t be enough for lengthening purposes as since lengthening post growth plate senesence is an abnormal task it probably requires very abnormal stimuli. It’s interesting to look at the device though.

The study mainly mentioned the technical design of the device and no analysis of the applications.

A Mechatronic Loading Device to Stimulate Bone Growth via a Human Knee

“This paper presents the design of an innovative device that applies dynamic mechanical load to human knee joints. Dynamic loading is employed by applying cyclic and periodic force on a target area. The repeated force loading was considered to be an effective modality for repair and rehabilitation of long bones that are subject to ailments like fractures, osteoporosis, osteoarthritis, etc. The proposed device design builds on the knowledge gained in previous animal and mechanical studies. It employs a modified slider-crank linkage mechanism actuated by a brushless Direct Current (DC) motor and provides uniform and cyclic force.”

Here’s an example of what slider crank linkage looks like:

“The functionality of the device was simulated in a software environment and the structural integrity was analyzed using a finite element method for the prototype construction. The device is controlled by a microcontroller that is programmed to provide the desired loading force at a predetermined frequency and for a specific duration. The device was successfully tested in various experiments for its usability and full functionality. The device works according to the requirements of force magnitude and operational frequency. This device is considered ready to be used for a clinical study to examine whether controlled knee-loading could be an effective regimen for treating the stated bone-related ailments{Hopefully bone length is one of those bone-related ailments unfortunately Ping Zhang’s name is not on this paper and he was always the one more interested in bone length}.”

“When a specific loading force is applied to the epiphyses of the femur and tibia, the trabecular bone tissue, which is characterized by axial stress resistance, resists this force from the opposite direction. This results in deformations in that area. These deformations create a variation of the fluid pressure in the intramedullary cavity. This pressure gradient allows the flow of fluids that carry essential nutrients to the bone cortex initiating osteoblast differentiation and osteogenesis, thus helping in repair and regeneration of the bone tissue. This unique reaction makes this procedure an effective treatment for bone rehabilitation. It helps in reduction of healing time of bone fractures and hastens recovery from bone-related injuries and diseases. The lateral stress application is also less strenuous to the knee bone and reduces the amount of force that needs to be applied to get this result.”

B is the force we’re looking for. The pressure generated by fluid flow not just on the bone but on the stem cells to initiate chondrogenic differentiation. The pressure on the intact bone may also allow the creation of cartilage canals to enable that requirement for a neo growth plate.

It’s also interesting to note that in the proposed knee loading device the load the entire lateral area of the epiphysis this may be a way to reduce slippage.

” it was decided that the proposed device should be robust enough to produce different magnitudes of linear force up to a maximum of 40 N”<-Since lengthening is not being considered in this study forces required for lengthening may be higher.

The device doesn’t look wide enough for the knee really. The dimensions of the device listed are:

Length: 0.3	m
Width: 0.1
Height: 0.2

There are about 39 inches in a meter so about 3.9 inches in width. I don’t know if that’s enough.

Also the device looks more like this kind of clamp:

Then the other clamps we’ve been using. Although you’d have to make new pads to actually adjust to knee. Well actually more like:

But the pipe gets in the way of getting around the knee. Although I’m not really sure that a pipe clamp is superior to the other clamps. I’m just pointing out that it’s the clamp that looks most like the design mentioned in the study.

Here’s some more details on the device:

Here’s an actual physical prototype:

Here’s an update on that device:

Analysis of Force Transmission by a Knee Loading Device from Skin and Soft Tissue to Knee Joint Elements

“Dynamic loading to a knee joint is considered to be an effective modality for enhancing the healing of long bones and cartilage that are subject to ailments like fractures, osteoarthritis, etc. We developed a knee loading device and tested it for force application. The device applies forces on the skin, whereas force transmitted to the knee joint elements is directly responsible for promoting the healing of bone and cartilage. However, it is not well understood how loads on the skin are transmitted to the cartilage, ligaments, and bone. Based on a CAD model of a human knee joint, we conducted a finite element analysis (FEA) for force transmission from the skin and soft tissue to a knee joint. In this study, 3D models of human knee joint elements were assembled in an FEA software package (SIMSOLID). A wide range of forces was applied to the skin with different thickness in order to obtain approximate force values transmitted from the skin to the joint elements. The maximum Von Mises stress and displacement distributions were estimated for different components of the knee joint. The results demonstrate that the high load bearing areas were located on the posterior portion of the cartilage. This prediction can be used to improve the design of the knee loading device.”

Step 1 for improving effectiveness of the device is to prove that it loads where it’s expected to be loading.

“A lateral application of force on the knee joint was found effective in protecting bone tissue in the areas of distal femur and proximal tibia of the knee bone. The effects of the stimulation of bone regeneration are not limited to the applied areas but are seen along the length of the long bone. When a specific loading force is applied to the epiphyses of the femur and tibia, the trabecular bone tissue, which is characterized by axial stress resistance, resists this force from the opposite direction.”

“This results in reversable deformations in that area. These deformations create a variation of the fluid pressure in the intramedullary cavity. This pressure gradient allows the flow of fluids that carry essential nutrients to the bone cortex initiating osteoblast differentiation and osteogenesis thus helping in repair and regeneration of the bone tissue“<-this pressure gradient at minimum should help carry nutrients to the growth plate at a minimum.

There’s a lot more information within the paper itself about potential joint loading device design.

Lowering Fbn1 levels may increase bone length(Marfan’s Syndrome)

Even though it mainly seems like it’s an active growth plate thing, it’s possible that FBN1 deficiency could stimulate neo-growth plate activation as it does stimulate TGF Beta activation and there’s ectopic tendon calcification. This Franscesco Ramirez scientist seems one to watch in understanding why Marfan’s Syndrome causes longitudinal bone overgrowth. If we understand why Marfan’s Syndrome causes overgrowth then maybe we can use that to our advantage especially if it is connected to tendons which are connected to muscles and are therefore easier to manipulate. Interesting that in the grant FBN1 inactivation is associated with greater TGF-Beta in the tendon/ligament but decreases TGF-Beta in the perichondrium.

TENDON-DEPENDENT CONTROL OF LONGITUDINAL BONE GROWTH

“Skeletal abnormalities caused by disproportioned bone overgrowth (LBO), are a common trait in Marfan syndrome (MFS), a connective tissue disease caused by mutations in the extracellular matrix (ECM) protein and TGFβ regulator fibrillin-1 (Fbn1). The cause of LBO in MFS is unknown and therapies are not available. Fibrillin-1 hypomorphic mouse model (Fbn1mgR/mgR) faithfully replicates MFS skeletal manifestations including elongated bones however, its early demise due aortic rupture limit the magnitude of LBO investigation.

To circumvent Fbn1mgR/mgR lethality and investigate the contribution of specific skeletal tissues to LBO, Fbn1 gene expression was targeted in developing limbs by crossing Fbn1Lox/Lox mice with Prx1-Cre, in or bone with Osx-Cre, in cartilage and perichondrium with Col2-Cre, in skeletal muscles with Mef2c-Cre, and ligaments and tendons with Scx-Cre. Bones length of Fbn1 conditional mice KO was measured and relevant histological, cellular and biomechanical parameters were assessed.

Fbn1Prx1−/+ and Fbn1Prx1−/− mice had longer limbs bones compared to WT mice and amount of fibrillin-1 in the limb matrix was inversely proportional to bone length. Interestingly, Fbn1 gene targeting in ligaments/tendons resulted in LBO, altered tissues’ mechanics and TGFβ-induced switch of tendon stem cells to chondrocytes{could we make tendon cells turn into chondrocytes as adults via TGF Beta?}. Gene targeting in other limb’s anatomical locations did not result in LBO thus ruling out the participation of surrounding tissues to this bone phenotype.

Fbn1 gene inactivation in ligament/tendon is associated with increased local TGFβ, altered biomechanical properties and LBO[longitudinal bone overgrowth]. As previously reported, ligaments/tendons respond to changes in mechanical load by increasing the levels and/or the activity of TGF-β while bones undergo morphological adaptation in response to muscle loads transmitted by tendons. We hypothesize that dysregulation of local TGFβ signaling and altered biomechanical properties of fibrillin-1 deficient ligaments/tendons affect endochondral ossification by improper load transmission to bone. By showing ligament/tendon-dependent regulation of postnatal longitudinal bone growth this study provides a paradigm-shift in tendon biology and it shades a new light on LBO pathophysiology in MFS, thus providing the bases for new pharmacological interventions for this and related skeletal conditions.”

So lower levels of Fbn1 means longer bone length and FBN1 deficient tendons and ligaments alter endochdondral ossification by altering load transmission to bone. We can alter load transmission via mechanical stimulation without altering FBN1.

Here’s a grant(2016) related to the subject:

TENDON-DEPENDENT CONTROL OF LONGITUDINAL BONE GROWTH

“disproportionate increase of longitudinal bone growth that causes serious malformations of the limbs, anterior chest and Spine is the clinical hallmark of patients afflicted with Marfan syndrome (MFS), a connective tissue disease caused by mutations in the extracellular matrix (ECM) protein and TGFβ regulator fibrillin-1. Our preliminary studies of mice with tissue-specific ablated Fbn1 gene activity have revealed an unsuspected causal relationship between tendon/ligament (T/L) dysfunction and longitudinal bone overgrowth (LBO). Specifically, (1) Fbn1 inactivation in T/L cells was necessary and sufficient to promote linear bone overgrowth associated with dysregulated growth plate (GP) gene expression; (2) fibrillin-1-deficient tendons displayed abnormal tissue architecture and impaired mechanical properties, particularly at bone- insertion sites; (3) the relative amount of fibrillin-1 correlated with discrete changes in tendon mechanics; (4) tendon-derived stem/progenitor cell (TSPC) cultures deficient for fibrillin-1 differentiated improperly as result of increased latent TGFβ activation; and (5) ectopic tendon calcification of fibrillin-1-deficient tendons was commonly observed. fibrillin-1 assemblies normally restrict GP-driven linear growth of neighboring bones by specifying the mechanical properties of tendons through the control of ECM organization and TGFB-regulated TSPC differentiation. Accordingly, the scope of our proposal is two-fold; first, to characterize how fibrillin-1 deficiency translates into tendon dysfunction and tendon-associated LBO, and second, to establish how local TGFB hyperactivity in tendons promote tissue degeneration thereby leading to excessive linear growth of the adjacent, structurally normal bones. To this end, we will characterize the expression of molecular and cellular determinants of tendon development and maturation in mice deficient for fibrillin-1 in T/L matrices, in addition to employing computational approaches to identify probable disease-causing molecular abnormalities in the GP of these tendon-defective animals (Aim 1); apply data-driven statistical models to determine how graded fibrillin-1 deficiencies correlate with tendon mechanics and associated LBO (Aim 2); and assess whether systemic TGFβ neutralization modifies tendon pathology and LBO severity in fibrillin-1-deficient mice (Aim 3). The results of these investigations are expected to substantially advance our limited understanding of tendon function in health and disease and implicitly, of the cellular, molecular and tissue factors that coordinate the postnatal growth of musculoskeletal tissues. ”

Here’s the updated 2020 grant.

It seems exactly the same as the 2016 grant.

Fibrillin-1 deficiency in the outer perichondrium causes longitudinal bone overgrowth in mice with Marfan syndrome

“A disproportionate tall stature is the most evident manifestation in Marfan syndrome (MFS), a multisystem condition caused by mutations in the extracellular protein and TGFβ modulator, fibrillin-1. Unlike cardiovascular manifestations, there has been little effort devoted to unravel the molecular mechanism responsible for long bone overgrowth in MFS. By combining the Cre-LoxP recombination system with metatarsal bone cultures, here we identify the outer layer of the perichondrium as the tissue responsible for long bone overgrowth in MFS mice{the perichondrium is less mature than the periosteum so it is unclear whether manipulating the periosteum would have any impact on longitudinal bone overgrowth}. Analyses of differentially expressed genes in the fibrillin-1-deficient perichondrium predicted that loss of TGFβ signaling may influence chondrogenesis in the neighboring epiphyseal growth plate (GP). Immunohistochemistry revealed that fibrillin-1 deficiency in the outer perichondrium is associated with decreased accumulation of latent TGFβ-binding proteins (LTBPs)-3 and -4, and reduced levels of phosphorylated (activated) Smad2. Consistent with these findings, mutant metatarsal bones grown in vitro were longer and released less TGFβ than the wild-type counterparts. Moreover, addition of recombinant TGFβ1 normalized linear growth of mutant metatarsal bones. We conclude that longitudinal bone overgrowth in MFS is accounted for by diminished sequestration of LTBP-3 and LTBP-4 into the fibrillin-1-deficient matrix of the outer perichondrium, which results in less TGFβ signaling locally and improper GP differentiation distally.”

<-I could not get this full paper. But also note that it’s the long bones that grow more with marfan’s syndrome so it’s possible that in different bones FBN1 has a different effect on TGFBeta

Interesting that less TGF Beta resulted in more longitudinal bone growth. I’ve always thought that TGF Beta is good for height. It could be that Smad 1/5/8 phosphorylation results in terminal differentiation. According to Inhibition of TGF-β Increases Bone Volume and Strength in a Mouse Model of Osteogenesis Imperfecta, inhibition of TGF Beta increases bone strength(no mention of bone length however).

According to this study by Ramirez:

Fibrillin-1 Regulates Skeletal Stem Cell Differentiation by Modulating TGFβ Activity Within the Marrow Niche

“limbs deficient for fibrillin-1 (Fbn1^Prx1–/– mice) is accounted for by premature depletion of MSCs and osteoprogenitor cells combined with constitutively enhanced bone resorption. “

Natural Height Growth

Cancer, Stem Cells, Regenerative Tissue Engineering, Transdifferentiation