Being Taller due to PEMF?

Pulsed Electromagnetic Field Therapy is used to treat the healing of non-union fractures(fractures that don't heal).  Now studying non-union fractures is very important to us height seekers as fractures heal as a result of endochondral ossification(stem cells, to chondrocytes, to hypertrophic chondrocytes, to apoptotic chondrocytes, to being invaded by osteoblasts).  The primary goal of Lateral Synovial Joint Loading, is to induce bone marrow stem cells to differentiate into chondrocytes from the epiphyseal bone marrow.  Any technique with applications on non-union fractures(fractures where endochondral ossification does not occur) will have applications on Lateral Synovial Joint Loading.  Because it means that before the non-union endochondral ossification did not occur, however after the stimulation endochondral ossification did occur.  Therefore, the stimulation may be effective at inducing endochondral ossification.

Effects of Pulsed Electromagnetic Fields on Human Osteoblastlike Cells (MG-63): A Pilot Study. 

"Pulsed electromagnetic fields (PEMFs) are used [on] two groups of MG63 cells. One group was treated with PEMFs for 18 hours whereas the second was maintained in the same culture condition without PEMFs (control).
PEMFs induced the upregulation of important genes related to bone formation (HOXA10, AKT1), genes at the transductional level (CALM1, P2RX7), genes for cytoskeletal components (FN1, VCL), and collagenous (COL1A2)[COL1A2 is the gene coding fibrous cartilage which isn't as important for height growth as hyaline cartilage but could be useful nonetheless] and noncollagenous (SPARC) matrix components. PEMF induced downregulation of genes related to the degradation of extracellular matrix (MMP-11, DUSP4). {none of these genes altered in LSJL(even col1a2)  indicating that PEMF can be synergestic with LSJL}
PEMFs appear to induce cell proliferation and differentiation. PEMFs promote extracellular matrix production and mineralization while decreasing matrix degradation and absorption." 

PEMF's can induce cellular proliferation and differentiation.  PEMF's alters the expression of anabolic genes which could have positive benefits on height growth.  Being taller thanks to PEMF is a definitive possibility.   Even though this study showed the effects of PEMF on osteoblastic cells there may be spillover benefits on chondrogenic cells like the degradation of MMP-11.  Also DUSP4 inhibits cellular proliferation so that again can have spillover chondrocyte and stem cell benefits.

"PEMFs determine signal transduction by means of intracellular release of Ca²⁺ leading to an increase in cytosolic Ca²⁺ and an increase in activated cytoskeletal calmodulin. PEMFs induce a dose-dependent increase in bone and cartilage differentiation, and upregulation of mRNA expression of extracellular matrix molecules, proteoglycan, and Type II collagen"<-dose dependent means that the stronger the stimulus, the more that the positive height increase benefits will be magnified. The genes mentioned therein are definitely related to height growth and show that PEMF may have a direct benefit on height.

Genes upregulated by PEMF that are up- (or down-regulated by LSJL):
H19
STK4(down)
CLCN2(down)

TIMP1

MFAP3L(down)

Genes downregulated by PEMF:

Effect of pulsed electromagnetic field on the proliferation and differentiation potential of human bone marrow mesenchymal stem cells. 

"PEMF stimulus was administered to BMMSCs[human bone marrow MSCs]  for 8 h per day during culture period. The PEMF applied consisted of 4.5 ms bursts repeating at 15 Hz, and each burst contained 20 pulses. Results showed that about 59% and 40% more viable BMMSC cells were obtained in the PEMF-exposed cultures at 24 h after plating for the seeding density of 1000 and 3000 cells/cm2, respectively. The growth rates of BMMSC during the exponential growth phase were not significantly affected, 20-60% higher cell densities were achieved during the exponentially expanding stage. Many newly divided cells appeared from 12 to 16 h after the PEMF treatment as revealed by the cell cycle analysis. PEMF exposure could enhance the BMMSC cell proliferation during the exponential phase and it possibly resulted from the shortening of the lag phase.  The PEMF-exposed BMMSC showed multi-lineage differentiation potential similar to the control group." 

"different characteristics of PEMF signals can reduce or enhance osteoclastogenesis of bone marrow cells"

"BMMSCcan repair a number of damaged tissues by the stimulation of mobilizing signals such as hypoxia, platelet-derived growth factor-AB (PDGF-AB) and insulin-like growth factor 1 (IGF-1)"

"voltage-gated delayed rectifier K+ current and Ca2+-activated K+ current channels were changed during progress from G1 to S phase, and functional expression of ion channels could regulate proliferation in undifferentiated rat mesenchymal stem cells. PEMF exposure changed the expression of ion channels and induced membrane hyperpolarization of BMMSCs and therefore resulted in the alteration of the cell cycle progression."

PEMFs can affect stem cell proliferation and this study shows that it can directly affect bone marrow stem cell proliferation and differentiation. In this study, only osteogenic differentiation was analyzed but PEMF helping with chondrogenic differentiation is likely.

Cytokine release from osteoblasts in response to different intensities of pulsed electromagnetic field stimulation. 

"We use an in-vitro osteoblast cell culture model to investigate the effects of low-frequency (7.5 Hz) pulsed electromagnetic field (PEMF) stimulation on osteoblast population, cytokines (prostaglandin E(2) (PGE(2))[PGE2 has effects on height growth], transforming growth factor beta1(TGFbeta1), and alkaline phosphatase (ALP) activity to find the optimal intensity of PEMF for osteoblast growth. PEMF can stimulate osteoblast growth, release of TGFbeta1, and, in addition, an increase of ALP activity. The synthesis and release of PGE(2) in the culture medium are reduced with increasing numbers of cells. Higher intensity does not necessarily mean increased osteoblast growth, and the most efficient intensity is about 2 mV/cm in this case." 

PEMF increased doubled osteoblast cell count.  PEMF increased PGE2 levels by 25%.  It also increased ALP levels by about 50%.

So PEMF has effects on transforming growth factor beta too?  This looks really promising for height growth.  The effect on cytokines may be a necessary side effect.  It's likely that for chondrogenic differentiation less than 2mV/cm will be used.   PEMF is really understudied in terms of inducing chondrogenic differentiation.  Right now, how much PEMF can help with growing taller is unknown.  TGF-Beta1 is what is responsible for initial chondrogenic differentiation which is key for height growth.

PEMF is for sale but I couldn't find a lot of options.  I know Amazon has a very strict refund policy that favors the consumer HealFast Therapy Equine PEMF Square Patch.  I can't verify how good this product is.  I also found Magnetic Therapy Set, Large.  It's cheap and it has pieces that are ideal of putting on the epiphysis of the bones.  You can see that they have one piece for the ankle and the other for the knee.

Here's a patent related to an electrical stimulation device.  The diagrams do show growth plate stimulation but they don't show if the device can get around chondrocyte finite proliferative capacity.  Two ways to get around it would be methods involving ECM secretion and inducing other stem cells not already a part of the growth plate to differentiate into chondrocytes. 

The patent mentions periosteal irritation, medullary plugging[likely refers to the medulla of the bone marrow so a hydrostatic pressure method], creation of an arteriovenous fistula[likely a hydrostatic pressure method], sympathetic denervation[removal of part of the sympathetic nervous system], heat, and foreign objects inserted into the epiphysis(like epiphyseal distraction) as previous attempts to grow taller. We'll have to do independent investigations on these things later.

"in vivo growth plate stimulation using signals of 2.5, 5.0, 10.0 and 20 volts peak-to-peak respectively"

" the group 1 animals (2.5 volts stimulation) experienced a 4.3% increase in length from 1.16 average ratio R/L to 1.21 average ratio R/L."

"For group 2 animals (5.0 volts stimulation) in Table II, a 9.2% increase in length was obtained, from 1.09 average ratio R/L to 1.19 average ratio R/L"<-so the benefit to length seems to be dose dependent.

"Table III and FIG. 4 illustrate that the group 3 animals (10.0 volts stimulation) experienced an 7.8% increase in bone length"<-the third group was not as much so results were biphasic.

"As shown in Table IV and FIG. 5, the group 4 animals (20.0 volts stimulation) experienced a 3.6% decrease in growth, from 1.16 average ratio R/L to 1.12 average ratio R/L. "<-further showing that results were biphasic

The study states that bimetallic strips were effective in inducing longitudinal growth[bimetallic strips convert temperature into mechanical stimuli]. A pulsed magnetic field of 1000mV was effective in inducing growth activity in a chick. An enhanced incorporation of 3H-thymidine is present in chondrocytes at 1166 V/cm^2 oscillating at 5 Hz.

The invention involves placing electrodes around the epiphysis and is AC[stands for alternating current which means that the current periodically changes direction likely to evade actin cytoskeleton adaptation] stimulation signal. Growth rate increase was demonstrated with the invention experimentation but it's uncertain whether that translates into higher adult height.

Here's another patent by Carl T Brighton:

Method and device for treating osteoarthritis and cartilage disease, defects, and injuries in the human hip

"Anatomic, analytical, and planar circuit models are developed to determining the impedances, conductivities, and current flows in the human hip joint and its surrounding soft tissues and skin that are required to produce a 20 mV/cm electric field in the synovium and articular cartilage of the human hip. "

"The endogenous electrical currents, originally thought to be due to phenomena occurring at the surface of crystals in the bone, have been shown to be due primarily to movement of fluid containing electrolytes in channels of the bone containing organic constituents with fixed negative charges, generating what are called “streaming potentials.” Studies of electrical phenomena in cartilage have demonstrated a mechanical-electrical transduction mechanism that resembles those described in bone, appearing when cartilage is mechanically compressed, causing movement of fluid and electrolytes over the surface of fixed negative charges in the proteoglycans and collagen in the cartilage matrix. These streaming potentials apparently serve a purpose in cartilage similar to that in bone, and, along with mechanical strain, lead to signal transduction that is capable of stimulating chondrocyte synthesis of matrix components."

"it has been conjectured that direct currents do not penetrate cellular membranes and that control is achieved via extracellular matrix differentiation"

Here's a study about MSC's becoming proliferative due to electric currents and this may translate to it being easier to induce chondrogenic differentiation and therefore height growth:

Degenerate wave and capacitive coupling increase human MSC invasion and proliferation while reducing cytotoxicity in an in vitro wound healing model.

"We compared the effects of direct current (DC), capacitive coupling (CC), pulsed electromagnetic field (PEMF) and degenerate wave (DW) on cellular activities including cytotoxicity, proliferation, cell-kinetics and apoptosis by stimulating human-BMMSCs 3 hours a day, up to 5 days. In addition, migration and invasion were assessed using fluorescence microscopy and by quantifying gene and protein expression. We found that DW had the greatest proliferative and least apoptotic and cytotoxic effects compared to other waveforms. DC, DW and CC stimulations resulted in a higher number of cells in S phase and G(2)/M phase as shown by cell cycle analysis. CC and DW caused more cells to invade collagen and showed increased MMP-2 {upregulated by LSJL} and MT1-MMP {upregulated by LSJL as MMP14} expression[remember MT1-MMP is responsible for the formation of new cartilage canals]. DC increased cellular migration in a scratch-wound assay and all ES waveforms enhanced expression of migratory genes with DC having the greatest effect. All ES treated cells showed similar progenitor potential as determined by MSC differentiation assay[so all forms of electrical stimulation increase the likelihood of chondrocyte differentiation which is good for a method like LSJL that wants to induce chondrocyte differentiation]. ES can influence BMMSCs activities, especially DW and CC, which show greater invasion and higher cell proliferation compared to other types of ES. "

Degenerate wave mixing involves using all three electromagnetic waves.  So we wouldn't just want PEMF but the other two forms of waves as well.

"Recent studies have illustrated the invasive capacity of human MSCs requiring MMP-2 and MT1-MMP"<-So in order to form new cartilage canals and growth plates you likely need MMP-2 and MT1-MMP.

"DC treated cells also significantly over expressed several migratory genes including SDF-1/CXCR4, PDGFB-R and TGF-β1-R, IGF-1 and IGF-1R"<-So electrical stimulation increases the number of TGF-Beta and IGF-1 receptors meaning that the stem cells are more sensitive to anabolic height growth proteins like TGF-Beta and IGF-1.

Although the stem cells were obtained from patients undergoing hip replacement surgery so there is a chance that this electrical stimulation may not increase the proteins of healthy bones in the same way.

Here's a study on the chondroprotective effects of PEMF but that doesn't mean that PEMF doesn't stimulate chondrogenesis itself:

Chondroprotective effects of pulsed electromagnetic fields on human cartilage explants.

"pulsed electromagnetic fields (PEMFs) [were used on] human articular cartilage explants from patients with osteoarthritis (OA).  Explants cultured in the absence and presence of IL-1β were treated with PEMF (1.5  mT, 75  Hz) or IGF-I alone or in combination for 1 and 7 days. PG synthesis and release were determined. Explants derived from lateral and medial condyles scored OA grades I and III, respectively. In OA grade I explants, after 7 days exposure, PEMF and IGF-I significantly increased (35) S-sulfate incorporation 49% and 53%, respectively, compared to control, and counteracted the inhibitory effect of IL 1β[remember proteoglycan sulfation can increase height] (0.01 ng/ml). The combined exposure to PEMF and IGF-I was additive in all conditions. Similar results were obtained in OA grade III cartilage explants. PEMF and IGF-I augment cartilage explant anabolic activities, increase PG synthesis, and counteract the catabolic activity of IL-1β[maybe PEMF can help keep growth plates open longer] in OA grades I and III."

"Interleukin-1β (IL-1β), the main catabolic cytokine in OA, exerts its activity by stimulating the increase of matrix metalloproteinase gene expression and by suppressing the synthesis of type II collagen and proteoglycans (PGs)"<-This interleukin could have effects in the epiphyseal bone marrow or in the growth plate inhibiting chondrogenesis thus if PEMF inhibits thus it may help increase height.

"In vivo studies it has been reported that PEMFs stimulate PG synthesis in rats during endochondral ossification"

"PEMF can act in concert with IGF-I"<-So PEMF doesn't stimulate chondrogenesis in the same manner as IGF-1 but that doesn't mean that PEMF can work in concert with other forms of chondrogenic stimulation.

Effects of low frequency electromagnetic fields on the chondrogenic differentiation of human mesenchymal stem cells.

"HMSCs at cell passages five and six were differentiated in pellet cultures in vitro under the addition of human fibroblast growth factor 2 (FGF-2) and human transforming growth factor-β(3) (TGF-β(3) )[we should be looking for ways to upregulate these compounds in the epiphyseal bone marrow]. Cultures were exposed to homogeneous sinusoidal extremely low-frequency magnetic fields (5 mT) produced by a solenoid or were kept in a control system. After 3 weeks of culture, chondrogenesis was assessed. Under EMF, hMSCs showed a significant increase in collagen type II expression at passage 6. Aggrecan and SOX9 expression did not change significantly after EMF exposure[so PEMF can not induce chondrogenesis on it's own but it can aid it]. Collagen type X expression decreased under electromagnetic stimulation[Type X collagen is important for a growth plate phenotype so this may mean that PEMF is better at inducing articular cartilage versus growth plate cartilage]. Pellet cultures at passage 5 that had been treated with EMF provided a higher glycosaminoglycan (GAG)/DNA content than cultures that had not been exposed to EMF. Chondrogenic differentiation of hMSCs may be improved by EMF regarding collagen type II expression and GAG content of cultures. EMF might be a way to stimulate and maintain chondrogenesis of hMSCs."

"The differentiation of hMSCs into chondrogenic cells requires a high initial cell density, three-dimensional (3-D) culture conditions and the application of growth factors. "<-Bone marrow is already 3D. We can upregulate growth factor expression and LSJL may help getting the stem cells together via fluid flow so chondrogenesis can occur.

"The Earth's static magnetic field in the long axis of the solenoid was measured at 45 µT. Low frequency sinusoidal electromagnetic fields with a frequency of 15 Hz and a flux density of 5 mT using a current of 1.2 A root mean square (RMS) were applied three times a day (for 45 min every 8 h) during the entire differentiation period of 21 days. "<-This is unreasonable to apply to humans and some electromagnetic fields may be generated already due to bone deformation caused by LSJL. So we need to know if PEMF is additive to LSJL?

[Low frequence pulsed electromagnetic fields induce chondrocyte-like cells differentiation of rat bone marrow-derived mesenchymal stem cells in vitro].

"LFPEMFs can promote chondrogenic differentiation of rat bone marrow-derived mesenchymal stem cells (rBMSCs) in vitro. The rBMSCs were isolated by adherence method and the third-generation of the rBMSCs were randomly divided into LFPEMFs groups, chondrocyte-induced group and control group. LFPEMFs groups with complete medium were exposed to 50Hz, 1mT PEMFs for 30 min every day, lasting for 10, 15 and 20 d, respectively. Chondrocyte-induced group were treated with chondrogenic media, while control groups were only cultured with complete medium. The mRNA and protein expression level of Col-II and aggrecan were significantly higher in the LFPEMFs group or chondrocyte-induced group, compared to the control group."

Couldn't get full study.

Dose-dependent new bone formation by extracorporeal shock wave application on the intact femur of rabbits.

"Thirty Chinchilla bastard rabbits [one year old] were randomly assigned to 5 groups (EFD[energy flux densities] 0.0, 0.35, 0.5, 0.9 and 1.2 mJ/mm2) and treated with extracorporeal shock waves at the distal femoral region (1,500 pulses; 1 Hz frequency).  Animals were injected with oxytetracycline at days 5-9 after shock wave application and sacrificed on day 10.

Application of shock waves induced new bone formation beginning with 0.5 mJ/mm2 EFD and increasing with 0.9 mJ/mm2 and 1.2 mJ/mm2. The latter EFD resulted in new bone formation also on the dorsal cortical bone; cortical fractures and periosteal detachment also occurred."

"Shock waves also lead to increased biomechanical stability of tendons reattached to bone . At the same time, high-energy shock waves have been shown to cause tendon damage in a dose-dependent manner"

Here's some images from the study

"Extracorporeal shock-wave application to the distal femoral region of the rabbit resulted in macroscopically detectable hematomas in the focus zone of every animal in the group treated with EFD 1.2 mJ/mm 2 and slight hematomas were detected in the animals treated with 0.9 mJ/mm 2 . No hematomas were found in any other animal."

Extracorporeal shockwave treatment cause periosteal bone formation and trabecular bone fracture.

"Cortical fractures were filled with fibrous tissue"<-this is image d shown above.  Fibrous tissue should still be capable of interstitial growth.

"trabecular fractures showed chondrogenic and osteogenic callus tissue"<-this is image i as shown above

Electromagnetic fields enhance chondrogenesis of human adipose-derived stem cells in a chondrogenic microenvironment in vitro.

"We tested the hypothesis that electromagnetic field (EMF) stimulation enhances chondrogenesis in human adipose-derived stem cells (ADSCs) in a chondrogenic microenvironment. A 2D hyaluronoan (HA)-coated well (2D-HA) and a 3D pellet culture system (3D-pellet) were used as chondrogenic microenvironments. The ADSCs were cultured in 2D-HA or 3D-pellet, and then treated with clinical-use pulse electromagnetic field (PEMF) or the innovative single-pulse electromagnetic field (SPEMF) stimulation. The cytotoxicity, cell viability, and chondrogenic and osteogenic differentiations were analyzed after PEMF or SPEMF treatment. The modules of PEMF and SPEMF stimulations used in this study did not cause cytotoxicity or alter cell viability in ADSCs. Both PEMF and SPEMF enhanced the chondrogenic gene expression (SOX-9, collagen type II and aggrecan) of ADSCs cultured in 2D-HA and 3D-pellet. The expressions of bone matrix genes (osteocalcin and collagen type I) of ADSCs were not changed after SPEMF treatment in 2D-HA and 3D-pellet; however, they were enhanced by PEMF treatment. Both PEMF and SPEMF increased the cartilaginous matrix (sulfate glycosaminoglycan; sGAG) deposition of ADSCs. However, PEMF treatment also increased mineralization of ADSCs, but SPEMF treatment did not. Both PEMF and SPEMF enhanced chondrogenic differentiation of ADSCs cultured in a chondrogenic microenvironment. SPEMF treatment enhanced ADSC chondrogenesis, but not osteogenesis, when the cells were cultured in a chondrogenic microenvironment. However, PEMF enhanced both osteogenesis and chondrogenesis under the same conditions. Thus, the combination of a chondrogenic microenvironment with SPEMF stimulation can promote chondrogenic differentiation of ADSCs, and may be applicable to articular cartilage tissue engineering."

Method for non-invasive electrical stimulation of epiphyseal plate growth

"Epiphyseal growth plate stimulation in the bone of a living body is achieved by applying electrodes non-invasively to a body and supplying to said electrodes an AC signal in the range of about 2.5 to 15 volts peak-to-peak at a frequency of about 20-100 KHz."

"supplying to said electrodes an alternating current stimulation signal having a generally symmetrical sine waveform with a voltage amplitude within the range of about 5 to 10 volts peak-to-peak and a frequency of about 60 KHz for a sufficient period of time to effect an increase in the growth of said bone as compared with any bone growth that would occur naturally."

Growth was optimized at 5Vpp which can be seen in the attached pdf.

These next two studies are by the author of the patent:

Up-regulation of bone morphogenetic proteins in cultured murine bone cells with use of specific electric fields.

"BMP-2 through BMP-8, gremlin, and noggin were all normally expressed by MC3T3-E1[osteoblast precursor cells] cells, and could be significantly up-regulated by specific and selective capacitively coupled electric fields. However, mRNA expression for BMP-2, 4, 5, 6, and 7 was consistently up-regulated several times higher than that for BMP-3 and BMP-8, gremlin, and noggin under identical conditions. Concomitantly, BMP-2 protein production and alkaline phosphatase activity were both significantly increased in the same electrically stimulated cultures"

Up-regulation of chondrocyte matrix genes and products by electric fields.

"a 0.5-hour, 20 mV/cm, signal at 60 kHz up-regulated aggrecan gene expression approximately eightfold using a 50% duty cycle, whereas Type II collagen gene expression was up-regulated approximately fivefold using an 8.3% duty cycle. Using a compound signal (a 0.5-hour continuous period plus multiple 1-hour periods of 50% duty cycle for 7 days) both proteoglycan and collagen accumulation in vitro were increased approximately fivefold and twofold, respectively. Also, the most effective capacitively coupled electric signal was different for each of the two molecules studied (aggrecan, 50% duty cycle and 4-hour response time; Type II collagen, 8.3% duty cycle and 6-hour response time). Selective up-regulation of gene expression and matrix accumulation of cartilage structural macromolecules (such as aggrecan and Type II collagen) with specific capacitively coupled fields occurs in vitro."

Couldn't get full study.

Use of Magnetic Forces to Promote Stem Cell Aggregation During Differentiation, and Cartilage Tissue Modeling.

"Magnetic forces induce cell condensation necessary for stem cell differentiation into cartilage and elicit the formation of a tissue-like structure: Magnetically driven fusion of aggregates assembled by micromagnets results in the formation of a continuous tissue layer containing abundant cartilage matrix."

"Chondrogenesis was occasionally impaired by high internalized iron concentrations"

"associate magnetic nanoparticles with MSC in order to endow the cells with magnetic properties."

Patent for Eletrical stimulation device:

 Alternating Electric Current Directs, Enhances, and Accelerates Mesenchymal Stem Cell Differentiation Into Either Osteoblasts or Chondrocytes But Not Adipocytes  

"the alternating electric current is a current in the range from 10 μA to 40 μA [and a frequency of 10Hz]." A sinusodal waveform is used.

"the alternating electric current is for either a continuous or intermittent pattern and a duration of application of 6 hours per day for up to 28 consecutive days."

In several of the experiment modalities tested chondrogenic differentiation was not stimulated.

Electrical stimulation of masseter muscles maintains condylar cartilage in long-term organ culture

"When condylar cartilage is maintained under nonfunctional organ culture conditions, its phenotypic expression is altered to a premature form with less expression of the type II collagen characteristic of mature chondroblasts. The aim of this study was to examine whether, by electrical stimulation of the major masticatory muscle, the masseter muscle, chondrogenic expression could be maintained{interesting that the masseter was stimulated and not the lateral pterygoid muscle} under organ culture conditions in which the jaws with the craniomandibular joint were cultured in one block. Sixty BALB/c mice of both sexes were divided randomly into three groups of equal size. Two groups were decapitated at the age of 5 days. The cranial base and mandible were dissected out in one block, and the explant was placed on its cut surface on a culture dish. The masseter muscles of the explants in one group were stimulated with an electric pulsing device delivering an AC current of a frequency of 0.7 Hz and an amplitude of 5V with hourly active and silent periods. Five experimental and five control explants were fixed after culture periods of 1, 3, 7, and 14 days. The mice in the third group were used as in vivo controls. By electrical stimulation of the masseter muscle, the phenotypic characteristics of the condylar chondroblasts, such as the deposition of type II collagen and the thickness of the cartilage layers{thickness of the cartilage layers would contribute to height if it were in the joints that contribute to height but the big question is whether articular cartilage endochondral ossification is stimulated}, closely resembled the situation in vivo, while the controls in a non-functional environment gradually lost their characteristic form."

Couldn't get the full study

The Anabolic Effects of Electrical Stimulation on Endochondral Bone Formation

"Electrical stimulation (ES) is used to treat non-union fractures and enhance spinal fusion rates. Its effects on endochondral ossification have been studied both in vitro and in vivo with evidence that it is capable of both inhibitory or stimulatory effects. Literature on its mechanism, however, is limited. The purpose of this study is to determine what effects direct current (DC) and capacitive coupling (CC) have on endochondral ossification and examine their mechanisms.

Methods: Thirty-four femurs from 3-week old C57BLK6 mice were divided into 3 groups (DC, CC, and control) and maintained in culture. After 2 days, the femurs were transferred daily to a silicone chamber with phosphate buffered saline. The DC and CC group received 10 minutes of DC at 10V and CC at 10VPP/16Hz, respectively; the control group received no current. After 7 days in culture, all specimens were either placed in ethyl alcohol followed by 4% paraformaldehyde for micro-computed tomography (μCT) analysis and histomorphometry, or frozen immediately in liquid N2 for gene expression analysis using quantitative polymerase chain reaction (qPCR). Each ES specimen was compared to the control using parametric non-paired t-test with p<0.05 considered significant.

Results: Both DC and CC treatments exhibited significantly increased bone volume/tissue volume and bone area compared to control. The DC group additionally had significantly increased trabecular thickness with decreased bone surface/bone volume while the CC group had a significant increase in the trabecular number and decrease in the trabecular spacing. Histomorphometric analysis of von Kossa-stained specimens demonstrated a significant decrease in growth plate height in DC samples. There was also a significant increase in resting/proliferative zones and decrease in hypertrophic zones in both the DC and CC groups compared to the control. On Safranin O-stained sections, there was deeper staining and an increased area of red in the sub-epiphyseal spongiosa in both DC and CC specimens compared to control. Mason’s trichrome-stained sections showed a significant increase in the osteoid area/bone area in both DC and CC groups compared to the control. Analysis of qPCR data demonstrated that DC stimulation significantly increased expression of alkaline phosphatase (ALP) and type I collagen (Col1) while CC stimulation dramatically increased expression of ALP, Sox9, and type X collagen (Col10).

Conclusion: This study corroborates previous evidence that ES is capable of stimulating endochondral bone formation. The variances in results between DC and CC, however, suggest they work through distinct mechanisms. The increase in trabecular thickness and Col1 may indicate that DC functions through an osteogenic pathway while the increase in trabecular number, Sox9, and Col10 expression in CC stimulation may indicate it functions through a chondrogenic pathway. Significance: ES may prove to be an alternative method of growth plate modulation; however, further investigation is warranted."

Electrical stimulation drives chondrogenesis of mesenchymal stem cells in the absence of exogenous growth factors

"Electrical stimulation (ES) is known to guide the development and regeneration of many tissues. However, although preclinical and clinical studies have demonstrated superior effects of ES on cartilage repair, the effects of ES on chondrogenesis remain elusive. Since mesenchyme stem cells (MSCs) have high therapeutic potential for cartilage regeneration, we investigated the actions of ES during chondrogenesis of MSCs. Herein, we demonstrate for the first time that ES enhances expression levels of chondrogenic markers, such as type II collagen, aggrecan, and Sox9, and decreases type I collagen levels, thereby inducing differentiation of MSCs into hyaline chondrogenic cells without the addition of exogenous growth factors. ES also induced MSC condensation and subsequent chondrogenesis by driving Ca2+/ATP oscillations, which are known to be essential for prechondrogenic condensation. In subsequent experiments, the effects of ES on ATP oscillations and chondrogenesis were dependent on extracellular ATP signaling via P2X4 receptors, and ES induced significant increases in TGF-β1 and BMP2 expression. However, the inhibition of TGF-β signaling blocked ES-driven condensation, whereas the inhibition of BMP signaling did not, indicating that TGF-β signaling but not BMP signaling mediates ES-driven condensation. These findings may contribute to the development of electrotherapeutic strategies for cartilage repair using MSCs."

"intracellular ATP levels oscillate during chondrogenic differentiation and the ATP oscillations play critical roles in prechondrogenic condensation, and that extracellular ATP signaling mediates the ATP oscillations during chondrogenesis"

"ES induces differentiation of MSCs into not fibrocartilaginous tissues but hyaline cartilaginous tissues"