Height Gain and the Piezoelectric Current

The loading regime in Lengthening of Mouse Hindlimbs with Joint Loading involved a PiezoActuator.  Sky of Easyheight.com often spoke of a piezoelectric current.  Bone deformation itself generates a PiezoElectric current but it's nice to have a PiezoActuator because there's a strain gauge directly attached to it.  You can also get a more precise idea of the current generated by a PiezoActuator but nothing that can be achieved by the PiezoActuator cannot be achieved by loading.  What is the Piezoelectric current and how can it affect chondrocytes to help us gain height and grow taller?

Polymeric piezoelectric actuator substrate for osteoblast mechanical stimulation.

"Bone mass distribution and structure are dependent on mechanical stress and adaptive response at cellular and tissue levels. Mechanical stimulation of bone induces new bone formation in vivo and increases the metabolic activity and gene expression of osteoblasts in culture.Osteoblasts were grown on the surface of a piezoelectric material, both in static and dynamic conditions at low frequencies, and total protein, cell viability and nitric oxide measurement comparisons are presented."

Piezoelectricity can induce osteogenic differentiation.

"It has been suggested that forces capable of inducing cell deformation induce changes in membrane channels and on protein structure and that ultimately, cytoskeleton deformation exerts direct influence on cell nuclei"<-so if your cytoskeleton has adapted to the deformation you will not grow taller by mechanical means


"The advantages of using piezoelectric material for bone cells stimulation are: the control of mechanical ranges stimulation only requires the control of the amount of electrical energy applied; the quicker answer to electric stimulus allows working in physiological frequencies, as are the ones used 1 and 3 Hz, respectively."<-piezoelectricity is used over mechanical methods because it's easier to control the amount of electrical energy applied but electrical energy corresponds to a mechanical range

"The bone has piezoelectric properties,... mechanical stress applied to dried bone produces polarization and submission of bone to an electric field originates strain."<-mechanical stress such as lateral epiphyseal loading generates electric potential within the bone

Cartilage and conversely chondrocytes have electrical potential too.

Electrical behavior of cartilage during loading.

"When cartilage is deformed, it becomes electrically polarized. At least two mechanisms seem to underlie this phenomenon, namely, a short-duration, high-amplitude, piezoelectric-like response and a longer-duration, lower-amplitude response secondary to streaming potentials. The polarity of articular cartilage during loading could hypothetically facilitate joint lubrication."

Chondrocyte polarization may prevent chondrocyte apoptosis.  Although chondrocyte apoptosis is not involved in epiphyseal fusion(because fusion is a separate process than growth plate senescence), slowing down apoptosis may allow for a longer hypertrophic phase.

The antioxidant resveratrol protects against chondrocyte apoptosis via effects on mitochondrial polarization and ATP production.

"Chondrocytes and cartilage explants were isolated from OA patients undergoing knee replacement surgery. Effects of resveratrol in the presence or absence of interleukin-1beta (IL-1beta) stimulation were assessed by measurement of prostaglandin E(2) (PGE(2)) and leukotriene B(4) (LTB(4)) synthesis, cyclooxygenase (COX) activity, matrix metalloproteinase (MMP) expression, and proteoglycan production. To explore the mechanisms of action of resveratrol, its effects on mitochondrial function and apoptosis were examined by assessing mitochondrial membrane potential, ATP levels, cytochrome c release, and annexin V staining.
Resveratrol inhibited both spontaneous and IL-1beta-induced PGE(2) production by >20% (P < 0.05) and by 80% (P < 0.001), respectively; similarly, LTB(4) production was reduced by >50% (P < 0.05). The production of PGE(2) was inhibited via a 70-90% suppression of COX-2 expression and enzyme activity (P < 0.05). Resveratrol also promoted anabolic effects in OA explant cultures, by elevating proteoglycan synthesis and decreasing production of MMPs 1, 3, and 13[MMP-3 is good but MMP-13 is bad so Resveratrol on a whole may have a positive benefit on height growth]. Pretreatment of OA chondrocytes with resveratrol blocked mitochondrial membrane depolarization, loss of mitochondrial biomass, and IL-1beta-induced ATP depletion. Similarly, IL-1beta-mediated induction of the apoptotic markers cytochrome c and annexin V was also inhibited by resveratrol. Exogenous addition of PGE(2) abolished the protective effects of resveratrol on mitochondrial membrane integrity, ATP levels, expression of apoptotic markers, and DNA fragmentation.
Resveratrol protects against IL-1beta-induced catabolic effects and prevents chondrocyte apoptosis via its inhibition of mitochondrial membrane depolarization and ATP depletion. These beneficial effects of resveratrol are due, in part, to its capacity to inhibit COX-2-derived PGE(2) synthesis. Resveratrol may therefore protect against oxidant injury and apoptosis, which are main features of progressive OA."

Resveratrol is available for sale: Biotivia Resveratrol Bioforte 250mg , Full Spectrum Resveratrol Supplement, Capsules, 60-Count Bottle.  However, Apoptosis is a necessary part of endochondral ossification and completely preventing it may reduce height growth(however, increasing chondrocyte time before apoptosis may help height growth).  Apoptosis plays a role in growth plate function and complete elimination may reduce adult height. 


Resveratrol may stunt growth by preventing needed chondrocyte apoptosis but mechanical loading like LSJL may enhance membrane polarization and inhibit apoptosis until the proper time.


What is the optimal charge for height growth in chondrocytes?

The effects of fixed electrical charge on chondrocyte behavior.

 "In this study we have compared the effects of negative and positive fixed charges on chondrocyte behavior in vitro. Electrical charges have been incorporated into oligo(poly(ethylene glycol) fumarate) (OPF) using small charged monomers such as sodium methacrylate (SMA) and (2-(methacryloyloxy) ethyl)-trimethyl ammonium chloride (MAETAC) to produce negatively and positively charged hydrogels, respectively. The physical and electrical properties of the hydrogels were characterized by measuring and calculating the swelling ratio and zeta potential, respectively. Our results revealed that the properties of these OPF modified hydrogels varied according to the concentration of charged monomers. Zeta potential measurements demonstrated that the electrical properties of the OPF hydrogel surfaces changed on incorporation of SMA and MAETAC and that these changes in electrical properties were dose-dependent. Attenuated total reflectance Fourier transform infrared spectroscopy was used to determine the hydrogel surface composition. To assess the effects of surface properties on chondrocyte behavior primary chondrocytes isolated from rabbit ears were seeded as a monolayer on top of the hydrogels. We demonstrated that the cells remained viable over 7days and began to proliferate while seeded on top of the hydrogels. Collagen type II staining was positive in all samples, however, the staining intensity was higher on negatively charged hydrogels. Similarly, glycosaminoglycan production was significantly higher on negatively charged hydrogels compared with a neutral hydrogel. Reverse transcriptase polymerase chain reaction showed up-regulation of collagen type II and down-regulation of collagen type I on the negatively charged hydrogels[negatively charged chondrocytes are more likely to differentiate into chondrocytes and less likely to differentiate into bone]. These findings indicate that charge plays an important role in establishing an appropriate environment for chondrocytes and, hence, in the engineering of cartilage. Thus, further investigations into charged hydrogels for cartilage tissue engineering is merited."

A negative charge may be better for height growth.  This may be important for PEMF related methods.

Regulation of immature cartilage growth by IGF-I, TGF-beta1, BMP-7, and PDGF-AB: role of metabolic balance between fixed charge and collagen network.

"Cartilage growth may involve alterations in the balance between the swelling tendency of proteoglycans and the restraining function of the collagen network. Growth factors, including IGF-I, TGF-beta1, BMP-7, and PDGF-AB, regulate chondrocyte metabolism and, consequently, may regulate cartilage growth. Immature bovine articular cartilage explants from the superficial and middle zones were incubated for 13 days in basal medium or medium supplemented with serum, IGF-I, TGF-beta1, BMP-7, or PDGF-AB. Variations in tissue size, accumulation of proteoglycan and collagen, and tensile properties were assessed. The inclusion of serum, IGF-I, or BMP-7 resulted in expansive tissue growth[IGF-1 and BMP-7 can help result in height growth], stimulation of proteoglycan deposition but not of collagen, and a diminution of tensile integrity. The regulation of cartilage metabolism by TGF-beta1 resulted in tissue homeostasis[too much TGF-Beta1 may result in a lack of height growth by encouraging homeostasis], with maintenance of size, composition, and function. Incubation in basal medium or with PDGF-AB resulted in small volumetric and compositional changes, but a marked decrease in tensile integrity. These results demonstrate that the phenotype of cartilage growth, and the associated balance between proteoglycan content and integrity of the collagen network, is regulated differentially by certain growth factors."

IGF-1 and BMP-7 are good for height growth and these relate to charges.

"While it is possible that tissues can grow appositionally in the absence of remodeling, interstitial tissue growth must involve both growth and remodeling since accretion of a single tissue component will change the overall tissue structure and mechanical properties."<-LSJL involves interstitial growth.  Since remodeling is needed total inhibition of catabolic materials is not recommended like osteoclasts, etc.

"a higher tendency to grow is expected in cartilage of the growth plate where the proportion of GAG is higher and tensile strength and modulus are lower than those of articular cartilage"<-GAGs are like chondroitin, hyaluronic acid, and glucosamine.

"Indeed, a relatively high rate of axial growth is observed in the growth plate in vivo (up to ~400 μm/day), as well as in vitro where larger increases in length were observed in cartilages containing one or more osteogenic zones as compared to that of entirely cartilaginous explants"<-cartilage grows better than it's surrounded by bone(Type I collagen).

"The presence of serum, IGF-I or BMP-7 resulted in deposition of GAG that exceeded the deposition of collagen, creating swelling pressures that were excessive relative to the restraining ability of the collagen network. This metabolic imbalance facilitated a relatively loose and weak collagen network that allowed volumetric expansion"<-IGF-1 and BMP-7 results in GAG deposition creating swelling pressures(like hydrostatic pressure of LSJL).  This weak network allowed for volumetric expansion(Growing Taller).

"The proteoglycan constituent of the extracellular matrix provides the tissue with a fixed negative charge that increases the tissue’s propensity to swell and to resist compressive loading"<-so increasing proteoglycan content increases the negative charge and causes more swelling(and by extension more hydrostatic pressure)

So the negative charge helps cause tissue swelling.  GAGs such as hyaluronic acid help with this swelling and thereby help height growth.  Remember, HGH growth plates have a high ratio of ECM to cells.

Bone has piezoeletric potential and that potential can be unleashed by mechanical loading or by a piezoactuator.  Chondrocytes seem to prefer a negative charge and that can be acquired by GAG accumulation such as hyaluronic acid et al.  GAG production seems to be encourage further by negative charge making a good positive feedback loop.

Compounds that inhibit depolirization like Resvatrol may not be recommended as some depolarization is required to allow for apoptosis which is required for chondrocyte hypertrophy(so ossification can occur).  Otherwise, eventually the entire bone would turn into cartilage.