Water is the Key to Growing Taller

Growing Taller involves bones growing longer.  Bone growth either involves direct bone deposition or chondrocyte growth.  Bone deposition usually only results in size increase when it occurs beneath the periosteum.  The flat bone of the skull is one of the few places in the body where such periosteal driven growth can increase height.  So that means that in terms of growing taller as an adult chondrocytes are the most promising candidate to increase height.  As there are numerous osteoblasts depositing bone within the body but the only dimension that increases in size are those dimensions beneath the periosteum.

Why can chondrocytes increase height whereas osteoblasts can't?

Both chondrocytes and osteoblasts can produce Extracellular Matrix.  They differ however in that chondrocytes ECM is much more hydrophillic than the ECM of bone.
Both chondrocytes and osteoblasts proliferate.
Osteoblasts are not traditionally thought of as undergoing hypertrophy and chondrocytes however are quite famous for it.  But, most cells respond to changes in water concentration by changing size.  Osteoblasts do hypertrophy.
Both Osteoblasts and Chondrocytes can undergo apoptosis.

So the key difference between osteoblasts and chondrocytes is the hydrophillic nature of the extracellular matrix.  The mechanism of apoptosis may differ between osteoblasts and chondrocytes as well.

A study called "The Osmotic sensitivity of rats..." found that the increase in cell size in chondrocytes was likely not due to swelling(caused by water) but rather due to hypertrophy. Higher concentrations of water still increased hypertrophy.  The study did find that the extracellular matrix was influenced by water and did show evidence of responding to changes in osmolarity.

LSJL increases the hydrostatic pressure which encourages chondrocyte proliferation rather than osteoblast proliferation.  Chondrocytes of course making you taller.  Osteoblasts respond to increases in hydrostatic pressure by producing TGF-Beta which encourages chondrogenic differentiation.  Cartilage is a lot more resistant to hydrostatic pressure than bone is.  So increasing hydrostatic pressure with LSJL induces a functional adaptation for cartilage growth within the bone that happens to make you taller.

Physically injecting water into the bone wouldn't work as that would create a hole for water to leak out of reducing hydrostatic pressure.  A study done by the LSJL scientists found that drilling a hole into bone eliminated the effectiveness of their joint loading modality.  Thus, we are left with mechanical means to induce higher levels of hydrostatic pressure unless someone can come up with a way to increase water concentration in the bone while still plugging the hole left by injection.

Chondrocytes can increase height without being next to periosteum, Osteoblasts typically only increase bone dimensions when new bone is deposited beneath the periosteum.

The main differences between chondrocytes and osteoblasts is the relationship of their extracellular matrix to water and the ability for chondrocytes to release this water stored within the ECM generating force when they undergo apoptosis.  This force may be what drives bone deformation and makes your bones your longer.

The study entitled "Mechanisms of cartilage replacement in bone..." explains in more detail how apoptic chondrocytes may generate energy that results in an increase in bone size.  The opening of the chondrocytes releases water.  This release generates energy that can push apart bone.  Osteoblasts do not have an ECM that absorbs water so their apoptosis is less dramatic.

A way to test this would be to implant something like a growth plate with cells that can absorb and secrete water without creating a gap in the bone.  You'd have to just implant the device in the marrow.

Why water is key to growing taller:

High Hydrostatic Pressure(high water levels) induces chondrocyte differentiation forming growth plates
The growth plates use water to hypertrophy and then release this water pushing the bone apart making you taller

A bunch of other chemicals and genes matter but it seems that water is the primary driving force behind height increase.  Thus, it would be worth exploring ways to manipulate water like temperature(LIPUS for one thing increases temperature in the applied areas), water retention(has to be within the bone), etc.

Here's a study about chondrocyte hypertrophy and the exact mechanisms in which it occurs:

Mechanics of chondrocyte hypertrophy.

"Chondrocyte hypertrophy dominates bone growth. Intra- and extracellular changes that are known to be induced by metabolically active hypertrophic chondrocytes are known to contribute to hypertrophy[these changes could produce a first that causes bone deformation]. However, it is unknown to which extent these mechanical conditions together can be held responsible for the total magnitude of hypertrophy. To address this aim requires a quantitative tool that captures the mechanical effects of collagen and proteoglycans, allows temporal changes in tissue composition, and can compute cell and tissue deformations[chondrocyte hypertrophy could induce deformation of the surrounding tissue which is bone]. After validating the numerical approach for studying hypertrophy, the model is applied to evaluate the direct mechanical effects of axial tension and compression on hypertrophy (Hueter-Volkmann principle) and to explore why hypertrophy is reduced in case of partially or fully compromised proteoglycan expression. Finally, a mechanical explanation is provided for the observation that chondrocytes do not hypertrophy when enzymatical collagen degradation is prohibited[The degradation of collagen changes the osmotic gradient] (S1Pcko knock-out mouse model). This paper shows that matrix turnover by metabolically active chondrocytes, together with externally applied mechanical conditions, can explain quantitatively the volumetric change of chondrocytes during hypertrophy. It provides a mechanistic explanation for the observation that collagen degradation results in chondrocyte hypertrophy[collagen degradation changes the osmotic balance and results in cell swelling thus possibly being the mean cause of hypertrophy], both under physiological and pathological conditions."


"During hypertrophy, collagenase activity and cellular and matrix changes are known to occur concurrently. The intracellular volumes occupied by organelles and cytoplasmic ground substance gradually increase,
together with the osmotic pressure generated by intracellular accumulation of organic osmolytes. Although quantification of the effects of cellular electro-chemo-mechanical properties has proven difficult, it is apparent that this can only be partially responsible for the ten fold volume change and four to five times increased cell height during hypertrophy"<-So the number of organic osmolytes[any compound that alters osmotic pressure] can be manipulated.  LSJL drives compounds via fluid flow so this could be part of the benefits of LSJL observed in rats.

"to keep up with such increase in cell height, the aligning extracellular matrix (ECM) needs to also stretch to 400–500% its original length."<-So chondrocyte hypertrophy stretches the ECM and possibly Type I collagen(bone as well) explaining height growth.

"The combined effect of changes in cell volume and matrix constitution is that the volume occupied by cells over the volume of ECM decreases from the early proliferative to the late hypertrophic zone. Yet, the total amount of matrix associated with one hypertrophic cell increases, with values ranging from 50 to 1000% depending on species, age and growth plate"

"The fraction of large proteoglycans per volume of matrix is largest around hypertrophic cells, which is especially interesting given that hyaluronan-mediated hydrostatic pressure causes lacuna expansion"<-LSJL increases hydrostatic pressure thus LSJL increases lacunae expansion

"Hypertrophic cells show active collagen metabolism. MMP’s are abundant in quantity and diversity around hypertrophic cells,while these cells continue synthesizing collagen"<-Why would hypertrophic cells continue to synthesize collagen if there are MMP's degrading it.  To change the osmotic pressure which results in force that exerts a stretch on the surrounding matrix(including type I collagen i.e. bone).

"We assume that the osmotic swelling pressure depends on the number of fixed charges in the proteoglycans per amount of extrafibrillar water"<-LSJL increases the fluid flow thus increasing the number of fixed charges in the proteoglycans.

"as a consequence of mechanical loading or tissue expansion, the amount of fixed charges per water volume may change."<-LSJL involves mechanical loading thus LSJL may change the number of fixed charges per water volume.

"By adding proteoglycans and/or collagen in this way, the newly derived initial solid fraction has become higher on the expense of the fluid fraction, while tissue volume does not change. During subsequent equilibration, total tissue volume increases as the fluid fraction is being restored."<-The solid part of the matrix includes type II collagen and proteoglycans.  ECM increases to restore osmotic pressure then when ECM is degraded the fluid in the matrix increases to restore osmotic pressure(thus release of fluid including water should generate some kind of force).  Then proteoglycans and type II collagen are restored once more to restore osmotic pressure.  This gradually leads to an increase in tissue volume.

"Catalytic enzymes are assumed to cleave a particular fraction of the collagen during a given time period. Meanwhile, collagen synthesis is ongoing. It is then assumed that newly formed collagen either self-assembles in an unstrained state, or otherwise induces changes in collagen fibrils, such that their strain is ameliorated."<-tissue formation occurs in such a way as to alleviate strain from newly-formed collagen this could be why bone becomes shaped in a certain way and thus applying strain to certain parts of the bone can manipulate bone growth.

"Cell hypertrophy is simulated by continuously running the model, by repeatedly adding proteoglycans
and collagen, followed by equilibration"<-so maybe you can keep the growth plates active by continuing to add proteoglycans and collagen.

This study is most promising to those with active growth plates but there are ways to increase serum proteoglycan number(by hyaluronic acid supplementation by example) and this can stimulate the cells in such a way as to be more likely to be chondrocytes.  Height growth is ultimately driven by changes in osmotic(water) pressure.

LSJL attempts to change osmotic intramedullary pressure in adult bone.

Here's a study related to osmotic pressure in articular cartilage.  We can apply some of the findings to growth plate cartilage.

Contribution of proteoglycan osmotic swelling pressure to the compressive properties of articular cartilage.

"The negatively charged proteoglycans (PG) provide compressive resistance to articular cartilage by means of their fixed charge density (FCD) and high osmotic pressure (π(PG)), and the collagen network (CN) provides the restraining forces to counterbalance π(PG)[we know that growth plate chondrocytes apply compressive resistance because the growth plate doesn't collapse to the weight of the body.  Height growth must involve the manipulation of Proteoglycans, Fixed Charged Density, Osmotic Pressure, and the Collagen network]. Our objectives in this work were to: 1), account for collagen intrafibrillar water when transforming biochemical measurements into a FCD-π(PG) relationship; 2), compute π(PG) and CN contributions to the compressive behavior of full-thickness cartilage during bovine growth (fetal, calf, and adult) and human adult aging (young and old); and 3), predict the effect of depth from the articular surface on π(PG) in human aging. Extrafibrillar FCD (FCD(EF)) and π(PG) increased with bovine growth due to an increase in CN concentration[as collagen content increased so did Fixed Charge Density and osmotic pressure], whereas PG concentration was steady. This maturation-related increase was amplified by compression. With normal human aging, FCD(EF) and π(PG) decreased[maybe this can be responsible for epiphyseal fusion, the Fixed Charged Density and Osmotic Pressure are no longer high enough to sustain the growth plate]. The π(PG)-values were close to equilibrium stress (σ(EQ)) in all bovine and young human cartilage, but were only approximately half of σ(EQ) in old human cartilage. Depth-related variations in the strain, FCD(EF), π(PG), and CN stress profiles in human cartilage suggested a functional deterioration of the superficial layer with aging. These results suggest the utility of the FCD-π(PG) relationship for elucidating the contribution of matrix macromolecules to the biomechanical properties of cartilage."

"Nearly 90% of PG is aggrecan, which complexes with hyaluronan (HA) and link protein to form large PG aggregates entrapped within the CN"<-Since so much of the proteoglycans are aggrecan that means that hyaluronic acid supplementation is event more beneficial as there's plenty of aggrecan to bind with.

"water is distributed between COL fibrils (intrafibrillar (IF)) and PG (extrafibrillar (EF)), and this water distribution varies with external stress applied to the tissue"<-LSJL provides external stress and modifies water distribution.

"Approximately twice the mass of KS[Keratan Sulfate] relative to CS[Chondroitin Sulfate] was equivalent to the same FCD. Also, π_PG[osmotic pressure] increased with an increasing CS/KS ratio, reflecting the charge difference between KS and CS"<-So the more Chondroitin Sulfate you have relative to Keratan Sulfate the more osmotic pressure you generate.  Thus providing more evidence that Chondroitin Sulfate supplementation may help you grow taller.

The reason that articular cartilage does not behave like a growth plate is that chondrocyte hypertrophy is prohibited when collagen degradation is inhibited.  To grow taller by endochondral ossification you need chondrocytes[hopefully induced by LSJL stimulation of chondrogenesis in the stem cells of the epiphyseal bone marrow], ECM[type II collagen], and collagen degradation[MMPs].

Induction of re-differentiation of passaged rat chondrocytes using a naturally obtained extracellular matrix microenvironment.

"Cell-derived matrix (CDM) [are] a physical microenvironment for chondrocyte re-differentiation. Once different cell types were cultured for 6 days and decellularized using detergents and enzymes, fibroblast-derived matrix (FDM), preosteoblast-derived matrix (PDM), and chondrocyte-derived matrix (CHDM) were obtained. From SEM observation, each CDM was found to resemble a fibrous mesh with self-assembled fibrils. Both FDM and PDM showed a more compact matrix structure compared to CHDM. numerous matrix proteins were quite different from each CDM in quantity and type. Specific matrix components, such as fibronectin, type I collagen, and laminin were detected. the water contact angle suggests that FDM is more hydrophilic than PDM or CHDM{Gelatin is also hydrophilic}. The proliferation of rat primary chondrocytes growing on CDMs was better than those growing on a plastic coverslip (control) or gelatin. Meanwhile synthesis of glycosaminoglycan (GAG) was more effective for passaged chondrocytes (P4) cultivated on CDMs, and the difference was significant compared to cells grown on the control or on gelatin. As for the gene expression of cartilage-specific markers, CDMs exhibited good chondrocyte re-differentiation with time: the dedifferentiating marker, type I collagen (Col I) was restrained, whereas the ratio between Col II and Col I, and between aggrecan and Col I, as an indicator of re-differentiation, was greatly improved. Col II showed a very positive signal in chondrocytes cultivated for 2 weeks on the CDMs. when 3D cell pellets made from either plate-grown or matrix-grown dedifferentiated chondrocytes (P5) were cultured for 4 weeks, matrix-grown cells were significantly better in the induction of chondrocyte re-differentiation, than those grown on the plate."

Type I collagen and Laminin was more abundant in FDM.

Water channel activity of plasma membrane affects chondrocyte migration and adhesion.

"Aquaporin-1 (AQP1){AQP5 is upregulated 3 fold in LSJL} water channel is expressed in human and equine articular chondrocytes. We investigated the expression of the AQP1 water channel in cultured articular chondrocytes from wild-type (AQP1(+/+)) and AQP1-knockout (AQP1(-/-)) mice and characterized its function in chondrocyte proliferation, migration and adhesion. Expression of AQP1 mRNA and protein was identified in freshly isolated neonatal AQP(+/+) chondrocytes. AQP1 protein [is localized] to the plasma membrane of AQP(+/+) chondrocytes in primary cultures. Relative plasma membrane water permeability of AQP1(+/+) chondrocytes was approximately 1.6-fold higher than that of AQP1(-/-) chondrocytes. The chondrocyte proliferation rate was not affected by AQP1 deletion. However, the serum-induced transwell migration rate of AQP1(-/-) chondrocytes was markedly reduced compared with AQP1(+/+) chondrocytes (16.2 +/- 0.2 vs 27.1 +/- 0.3%, respectively). Cell adhesion to type II collagen-coated plates was also significantly reduced in AQP1(-/-) chondrocytes compared with AQP1(+/+) chondrocytes (38.1 +/- 0.3 vs 51 +/- 1%, respectively). AQP1-mediated plasma membrane water permeability plays an important role in chondrocyte migration and adhesion."

"The aquaporins (AQPs) are a family of water-transporting proteins with 13 homologous members"

"AQP-mediated high plasma membrane water permeability enhances cell migration"

Increased differentiation capacity of bone marrow-derived mesenchymal stem cells in aquaporin-5 deficiency., states that chondrogenic differentiation increases upon AQP5 deficiency which is consistent if AQP5 enhances migration and proliferation both of which have inverse relationships to differentiation.