New Jeffrey Baron study about Growth Plate Regulation

Jeffrey Baron is one of the scientists studying growth plate senescence so his insights could be very helpful in stopping growth plate closure and forming new growth plates.

Recent insights into the regulation of the growth plate.

“Expression in the resting and the proliferative zone was compared to identify pathways involved in the differentiation of resting zone to proliferative zone chondrocytes. This analysis implicated vitamin D receptor / retinoid x receptor (VDR/RXR) activation, platelet-derived growth factor (PDGF) signaling, BMP signaling, and notch signaling. Similar analysis of the proliferative to hypertrophic differentiation step implicated p53 signaling, ephrin receptor signaling, oncostatin M signaling, and BMP signaling”

“evidence for a BMP signaling gradient across the growth plate with the greatest BMP signaling occurring in the hypertrophic zone and the least in the resting zone”<-Maybe this BMP signaling gradient is caused by some other gradient like a pressure gradient.   We know that LSJL induces a gradient so this could be related to LSJL methodology.

“immunolocalization of phosphorylated SMAD-1, – 5, and -8 in the growth plate increases with increasing distance from the epiphysis”

“Low levels of BMP signaling in the resting zone may help maintain the progenitor cell state. Farther from the epiphysis, greater BMP signaling may induce differentiation to proliferative chondrocytes and, even farther from the epiphysis, yet greater BMP signaling may induce terminal differentiation to hypertrophic chondrocytes.”

The BMP gradient described in figure 2 of the study:

Resting Zone: Bmp-3, Gremlin, Chordin

Proliferative Zone:  GDF10, BMP7

Hypertrophic Zone: Bmp2, BMP6

“In the embryonic skeleton, PTHrP is secreted by periarticular chondrocytes of long bones. PTHrP diffuses across the growth cartilage maintaining chondrocytes in the proliferative state. Cells more distant from the source of PTHrP undergo hypertrophic differentiation.”<-LSJL also puts load on the articular cartilage.  Maybe LSJL induces the release of PTHrP.

“The prehypertrophic and hypertrophic chondrocytes then secrete Indian hedgehog (Ihh), which has a negative-feedback effect on PTHrP production and also independent effects on chondrocyte differentiation. More recent evidence suggests that the Ihh–PTHrP system is maintained in postnatal growth plate but the PTHrP source shifts to the resting zone”<-Some more on PTHrP and chondrocyte differentiation.

Genes involved in human growth plate function:

“the IHH-PTHrP system (GLI2, IHH, HHIP, PTCH1, and PTHLH lie within GWAS loci), BMP/TGF superfamily signaling (TGFB2, BMP6, LTBP3, NOG, BMP2, GDF5), C-type natriuretic peptide signaling (NPPC, PRKG2, NPR3), GH-IGF-I signaling (IGF2BP2, IGF2BP3, IGF1R), and FGF signaling (FGF18).”

“At the molecular level, CNP inhibits the extracellular signal-regulated kinase (ERK) and p38 mitogen activated protein kinase (MAPK) pathways, therefore counteracting the growth-inhibitory downstream signaling of fibroblast growth factor (FGF) in the growth plate”

“BNP [which is involved in growth plate regulation] is transcriptionally regulated by the transcription factor SHOX [which also regulates the growth plate]”

“FGFR1 and FGFR3 signaling are growth-inhibiting, while FGFR2 signaling is growth-promoting. Cartilage-specific (Col2a1-Cre) inactivation of Fgfr1 in mice showed a transient increase height in hypertrophic zone, and delayed terminal differentiation of hypertrophic chondrocytes. However, increase in adult body length has not been reported. In contrast, inactivation of Fgfr2 in the mesenchymal condensations (Dermo1-cre), which affects both the osteoblast and chondrocyte lineages, resulted in mice with skeletal dwarfism”

“transgenic mice with activated Fgfr3 in the growth plate show reduced chondrocyte proliferation, decreased numbers of hypertrophic chondrocytes and decreased height of the hypertrophic zone, while Fgfr3 knockout mice showed increased chondrocyte proliferation, increased height of hypertrophic zone, and increased skeletal growth”

“Fgf9 and Fgf18 promote chondrocyte proliferation during early development of the growth plate, but then function to inhibit chondrocyte proliferation and promote hypertrophic differentiation at later stages of development.”

“FGF21 can activate FGFR1 and FGFR3, both of which elicit growth-inhibitory signaling”

“Fgf21 knockout mice showed no significant difference in body weight and body length as compared to wild type mice”<-FGF21 may play a role in fasting induced growth inhibition.  So FGF21 would be a safe target to inhibit for growth.

“GH has no apparent role in fetal growth, despite the presence of its receptor (GHR) in embryos”

“mice lacking both the GH receptor and IGF-I have shorter bones than mice lacking only IGF-I, suggesting that GH, at least at a super-physiologic circulating concentrations, has an IGF-I-independent effect on bone growth”

“GH-induced Socs2-/-  metatarsal bone growth is not accompanied by increase in Igf1 or Igfbp3 transcript levels, and occurred in the presence of an IGF-I receptor inhibitor”

Successful Implantation of Entire 3D-Printed Skull Bone Due To Disorder Causing Increase In Skull Thickness

Successful Implantation of Entire 3D-Printed Skull Bone Due To Disorder Causing Increase In Skull Thickness

3D-Printed Skull BoneThere are places on the internet which I read up on which reveal some of the most interesting medical and scientific innovations going on in our time. This recent story I heard shows that there are mays to increase our overall height than just alternations to our limbs.

I remember hearing stories many years ago about how young potential sumo wrestlers who might be just a few cms shorter than the height requirement cut-off point would go through type of scalp lifting/removal surgery to put some type of permanent, semi-hard implant into their scalp to give them that extra thickness so that they can qualify to train to become a future sumo wrestler. Back then I thought it was insane but now I sort of understand why people do that kind of thing.

This surgery obvious takes things to a completely different level. I’ve personally done research on skull and brain surgeries so I know about some of the most aggressive forms of head manipulation and cutting techniques that are out there. This one is absolutely fascinating.

The young woman who was just 22 years old seemed to have this disorder that causes the her skull bones to become thicker and thicker over time. This seems to be an example of appositional growth, or just calcium absorption and deposition on the inner side of the skull.

We are of course assuming that it was not the outside of the skull that was getting the extra layering, since it says that the increase in thickness of the skull bone started to pinch down on her optic nerve which was ready to completely blind her. The surgery was performed in this university called University Medical Centre Utrecht.

This story was huge just last month and was shared extensively over social media so some of you might have already heard about it. The implant that was placed was a type of plastic cover. Obviously the medical issue of whether the plastic cover would be durable enough to last for over the patient’s entire life was raised. Would she have to go back in 5, 10, 30 years to get it replaced? Maybe it is made from a biodegradable material so all that is needed is to cover the plastic with some calcium paste and let it solidify over time?

The sources I got the story from are from in the article “Neurosurgeons successfully implant 3D printed skull” & “Neurosurgeons Have Successfully Implanted the First 3-D Printed Skull Into a Woman’s Head

Environmental Inputs on Longitudinal Bone Growth

Environmental temperature impact on bone and cartilage growth.

“Environmental modulation of tissue temperature can have direct and immediate consequences on cell proliferation, metabolism, matrix production, and mineralization in cartilage. Temperature can also indirectly influence cartilage growth by modulating circulating levels and delivery routes of essential hormones and paracrine regulators.”

environmental inputsThe arrows in white are the functional purposes of the bone.  In red are the factors that can affect bone length.  Bone adapts to the demands placed upon but not always in the way we want.  It doesn’t matter if stretching to us makes sense to use to produce longer bones.  It makes what the bones think.  The bone thinks to think:  I’m being stretched I should grow longer.  We need to recreate specific stimulus in the past that produces the desired results.  For example, the growth plate which results in longitudinal bone growth is a result of mesenchymal condensation of progenitor cells.  The goal of LSJL is to create a stimuli of hydrostatic pressure and shear strain that has been shown to induce mesenchymal condensation in adult mesenchymal stem cells and in turn induce chondrogenesis.

“Chondrocytes differentiate from a reserve pool of round quiescent cells into flattened columns of proliferating cells, which then mature into large terminally differentiated hypertrophic cells, and are ultimately replaced with mineral at the chondro-osseous junction where bone-forming osteoblasts invade from the metaphyseal vasculature”

“limb length correlates with temperature and latitude”

“limb length can be modified within a single generation by rearing young littermate animals at warm and cold temperatures during the postnatal growth period”

“Growth plate morphology was unexpectedly similar at cold and warm temperatures.  There were no major appreciable differences in overall size, shape, or organization of the cartilage.”

“variation in adult long bone length between inbred mouse strains was primarily generated by growth rate differences that occurred during a phase of rapid bone elongation between 3 and 5 weeks age.”<-it could be that lack of enough temperature is a limiting factor on height growth only in the most rapid periods of growth.

Usually these temperature studies are capped at one point in temperature so it’s hard to see if there’s an equilibrium temperature.

“normal capillary blood flow in the skin of the tibia (lower leg) was significantly higher than that in the metatarsal (foot) region, indicating a natural proximal-distal gradient in blood supply.”

” at high temperature extremes outside of a tolerable physiological range, heat does negatively impact body growth.”

“Without countercurrent heat exchangers in a cold environment, blood will rapidly lose temperature as it flows to the distal-most parts of the appendages. Core temperature would consequently drop as cool venous blood returns to the body core. One mechanism to combat a whole body cooling effect is to reduce total outflow of blood flow to the appendages by regulating vasomotor tone”

“This initially perplexing finding (no major differences in morphology of the growth plate when bone lengths did differ) may actually be quite informative as to the mechanism of the growth effect. One possibility is that a complex change in gene expression, cell metabolic activity, and/or maturation rate could contribute to the growth rate differences without changing the superficial appearance of the cartilage. The other corresponding possibility is that the growth rate differences were too slight to detect in the static histology “snapshot.” The total difference in tibia bone length between warm and cold was approximately 370 μm”

The study mentions that heat can induce bone marrow expansion.  Equilibrium temperature can increase calcium uptake.  Cold temperature induces endoplasmic reticulum stress.  HSP70 expression is affected by temperature.  Hydrostatic Pressure also increases HSP70.  HMGB1 is negatively correlated with temperature.  HMGB1 seems to encourage the early stages of chondrogenesis.  This would be a good thing in the formation of the growth but could be a bad thing in the later stages as it may effect the degree of endochondral ossification of the growth plate reducing longitudinal bone growth.  But mice that lack HMGB1 have shorter bones.  Heat also can incude TRPV4 activation.  TRPV4 may modulate bone elongation by affecting cell volume in chondrocytes.  However, continuously active TRPV4 mutants have abnormal endochondral ossification and reduced longitudinal bone growth.

” warm temperature could facilitate bone elongation by increasing the number of cells that could become bone forming osteoblasts at the chondro-osseous junction. There is also evidence that cold could limit bone elongation by directly inhibiting osteoblast activity.”<-Which would mean that heat wouldn’t play a role in neo-growth plate formation.

” leptin deficiency produces a contrasting phenotype in the limb bones and spine (short femurs and long spine)”

“Blood flow could be permanently modified by temperature through the route of new vessel formation, or angiogenesis”

“disrupted blood flow markedly impairs limb growth”

“surgical obstruction of the principal nutrient artery within the tibia marrow cavity of rabbits caused blood to be shunted toward the metaphyseal vessels and increased blood flow to the growth plate. Within three months after the surgery, the operated tibia had grown significantly longer compared to the contralateral side that received the normal blood supply”

So blood flow seems to be the most promising way to increase longitudinal bone growth and inducing new growth plates is not a ruled out effect of increasing blood flow so that LSJL likely increases blood flow is a good sign.

How To Look Taller By Wearing Thick Heeled Height Increasing Insoles

How To Look Taller By Wearing Thick Heeled Height Increasing Insoles

Height Increasing InsoleSometimes maybe the easiest thing for us to do is to just to give a temporary fix to our psychological issues with our short stature. The simplest way that I can think of on how to make ourselves at least look taller is to wear shoes with thicker heels, those shoes known as lifts, or some type of height increasing insoles.

Previously, I had reviewed before the YOKO and the KIMI height increasing insoles (Available Here) which are exactly the same product, with a slightly different name., as well as these in-sock height increasing arched insoles. (Review Available Here). Those products are no longer prevalent on the internet was very popular and marketed extensively maybe 5 years ago, when the internet was a younger entity. Of course, they never worked. Putting the insoles inside one’s shoes will make one look taller to other people, but it won’t stimulate some type of secret pressure point to release excess growth hormones to make a person grow taller. That is not going to happen.

These are the new models of thick heeled insoles sold in the market today…

Height Increase Elevator Shoes Insole (by Calden) – Price: $7-$8

Height Increasing InsoleDescription: It seems to be able to give the user around 1-1.5 inches of extra height. This particular model is made of two pieces. The 2 pieces are detachable from each other. The top plastic piece gives an extra height of around 1 inch, and the bottom part gives an additonal 0.5 an inch. If the size of the insole is too long or wide, you can take some scissors and trim the edges to fit for the right shoe size. Since the lift is probably going to be stuffed secretly in one’s shoes, that will take up space where the feet is usually be at. This means that you would actually need to get a deeper or larger sized shoe than – Read more

Honeycomb Shaped Gel Elevator Shoes Half Insole – Price: $7.50

Honeycomb Shaped Gel Elevator Shoes Half InsoleDescription: This type of insole is actually known as a half-insole. It is just “half” of the entire thing because it is only for the back part of the feet. When a person walks with this thing stuffed in the soles of the inside of the shoe, it would probably feel like their feet is raised in the back. The net result is that from the outside, appearance wise, they would look to be slightly taller. We are not sure how comfortable this product would actually be for any person since it might cause the arch of the feet to become bent in the wrong angle causing long term feet problems. A common problem is what is known as FlatfeetRead more

Half Elevator Insole for Men (by Calden) – Price: $7

Half Elevator Insole for MenDescription: This model of elevator insole is also of the half-insole variety. This particular model has a function of increasing a person’s height by upwards of even 1/2 an inch. I am a little surprised by the model since from the pictures we see from the side view, it looks kind of thin. The material that this model called the half elevator insole is made from is a ultra-light weight foam. I remember seeing models of this type in some large retail stores in the US but it is very prevalent in Asian countries like South Korea where wearing stuffing height increasing insoles is commonly practiced. This rather thin type might be – Read more

Height Lifting Inserts (For both Men and Women) – Price: $17

Height Lifting InsertsDescription: Our first impression of this type of insole from just the first picture is that it is one which we have seen before. We are referring to the elevator shoes insoles, which was the very first quick review we had done. Notice how in both this model, and the original model we looked at they have almost the exact same design. There is two main pieces, with the thicker piece being on top. The only noticeable difference we can see from just looking at the pictures is the back area. This model has a type of glossy plastic back side. I would guess that the plastic in the back is for support when a person is walking – Read more

The WSWS 3-Layer Air Cushion Insole – Price: $18-$20

WSWS 3-Layer Air CushionDescription: Out of all the types of foam insoles we have seen so far, this model is the most expensive of them all. However, it makes up for the price with a degree of assured quality in the durability of the insole. The seller of the product is WSWS. The extra cost is also explained by the fact that there is 3 separate layers to the increased thickness. It translates to a total of 2 and a half inches. That is a lot more than any other insoles sold out there. However, with that type of increase, the big problem turns into us asking the question “How will we ever be able to walk in a regular shoe with that also stuffed inside?” – Read more

LiftKit Lo-Top Insoles (For Men) – Price: $25-$30

LiftKit Lo-Top InsolesDescription: This was the one model of insoles which we have seen before. It is called the LiftKit Lo-Tope Insole. Notice from the picture how well it is designed. I personally like it for its sloping design. This means that the feet that goes on top of it won’t feel any discomfort, unlike putting a half-arch underneath it. The human feet does require an arch, but the soft foam nature of all of these insoles suggest that when you stand up on the insoles, the foam will give way to the contours of your feet. If we take into consideration the give of the foam, there will be obviously a decrease in the height gained. – Read more

The LiftKits Universal Insole – Price: $23-$27

LiftKits Universal InsoleDescription: This model is one of the half dozen or so models sold by LiftKits. Most of the other models are designed for either men or women, but this model is unisex, hence the name the LiftKits Universal Insole. This model would give a person up to 1 1/4th of an inch in height increase. Of course, that is if you are using of the two separate pieces on top of each other. The top thick heel would give 3/4th of an inch, and the bottom one would give half an inch. I personally am not a big fan of the half-insole types, especially if they are too high up. If you are going to be wearing those type, I suggest that the - Read more

Rosallini Nest Design Flannel Heel Gel Insoles – Price: $4

Rosallini Nest Design Flannel Heel GelDescription: Whereas before, we reviewed basically two sellers or middleman of thick heeled insoles, Calden and LiftKits, this other model type is sold by Rosallini. We have never heard of this seller or distributor. The type of heeled gel insoles that is sold by Rosallini, which seems to be an all purpose middle man of stick retail products, including jewelry, accesories, and novelty items. I took a look at this exact model called the Nest Deisgn Flannel Heel gel and was not very impressived. The heel are just too thick and tall and bulky for a person to use without hurting themselves. It would however give - Read more

Silicon Gel Insert Insole Pads – Price: $4

Silicon Gel Insert Insole PadsDescription: This is not an insole, but still a type of pad you would stick inside a sneaker or dress shoe to provide a slight bit of height. The pad is obviously clear or transparent, and the material used is silicone, which gives it a much more malleable and deformable quality to it. For each of the pairs of silicon gel insert pads, there will be 5 different layers, which will each provide a little less than 1/4th of an inch. The 5 layers together will give a person who is standing up just about 1 inch of height increase. I personally have bought one of these before from a street vendor in Asia and tried them on. The feeling was - Read more

How To Wear These Insoles Comfortably

The way that a lot of these insoles are shaped, there would be no way to even fit them on the back of the inside of any shoe. Some of the insoles claim to be able to raise a person’s height by even 2 and a half inches. There are many shoes where the top edge don’t even reach that tall. If you tried to put that insole inside, it might be too wide or too tall for the shoe. If the insole does get inside, maybe there will be no more room for a person to put their own feet in.

Even if you could get your feet inside the space above the insoles in the shoes, it might be too tight for your feet. When you finally do manage to stand up, walking with the insoles might be extremely uncomfortable. That is why I wanted to talk about a few tips on how a person who plans to wear these insoles can relief discomfort or pain.

Tip #1: Pick a shoe size around 2-3 sizes bigger than one’s feet. That increased shoe size, will give more width and length to fit the insoles inside. The size increase would also mean the shoe would be slightly taller or deeper. When you put the insoles in, you will still have enough room for the insoles.

Tip #2: Wear comfortable socks. Some of the insoles might have a type of foam or gel that would be sticky to the soles of the feet. Wear socks.

Tip #3: Buy & put around 3-4 insoles stacked together. Most insoles sold will give only about 1/4th of an inch in height, 1 cm at most. To get at least 1 inch of noticeable change in your appearance, you would want to get more than 1.

Tip #4: Avoid the gel type of insoles. They are too soft and if you use them too long, they can loss the structural integrity and become squished, turning the insole into a thin pancake, providing nothing at all.

Tip #5: Avoid the half insoles. The half insoles if they are stacked on top of each other will create a type of wdge shape, which has a very big angle. There would be no way a person can put their feet inside the shoe with a high wedge.

Some Background on Wearing Insoles and Arches To Look Taller

I remember that Sky, the creator of the website LimbCenter.Org even did a comparison on how easy and well it would be to just put thick heel insoles into a person’s shoes to gain upwards of 1-2 inches of temporary height. He concluded that the the result of just putting a thick heeled insole into the shoes did have a small effect. It would seem that 1 of those insoles would give maybe 1/4-1/8th of an inch in height increase, which is almost completely unnoticeable to most people, unless a person was standing next to a stadiometer or something. I sort of say that if a person just wanted to look taller temporarily, add more than just 1 insole in there.

There has even been at least one really popular and well accepted company started in recent years by a semi-famous celebrity male model Derek White, who started the company LiftKits. His product is the Liftkit Insoles, which is another type of insole. What sets his models apart from the others in the market has been the way the layers of the insoles snap on together, which is sort of a clever spin on an old idea. We did a review on the Lift Kits in a very old post (Available Here). Since this Derek White guy never claimed that the insoles he sells can actually make a person become taller, but just look taller, we fully supported him and his endeavor. I personally don’t seem anything wrong with promoting and selling some of these insoles, as long as one is being completely honest what what the product can actually deliver and provide value for the customer.

For a little bit of perspective to realize how big the craze of wearing insoles for increased height are, look at this video I uploaded more than a year ago. I found this line of insoles being sold on the side of a local street in Seoul, South Korea. The guy who was selling the thick heeled cushions seemed very nonchalant of this practice.

Using Extracorporeal Shockwave Lithotripsy or Lasers To Create Minimally Invasive Microfractures To Lengthen Cortical Bone

Using Extracorporeal Shockwave Lithotripsy or Lasers To Create Minimally Invasive Microfractures To Lengthen Cortical Bone

Extracorporeal Shockwave LithotripsyRecently I went back on the kick to learn medicine again, and I was told by a post/article written on the medical website KevinMD (Available Here) to read the following three medical memoir type books, which supposedly most medical students have read, or will read at some point. So I bought two of them through Kindle and started to read over them. The books are…

  1. Mountains Beyond Mountains: The Quest of Paul Farmer, a Man Who Would Cure the World - by Tracy Kidder
  2. Complications - by Atul Gawande
  3. My Own Country - by Abraham Verghese

The third book didn’t interest me that much since I have done research with a startup company years ago on an HIV Vaccine used in cocktails. The other 2 books were much more interesting. It was in the book Complications by Atul Gawande, who talks about how residents and interns who choose the surgical path still make mistakes and will always need to force themselves to practice in a trial and error mode to learn how to perform various medical techniques properly.

One thing he mentioned in the book was how his father was also a physician, a urology. Apparently his father had to learn over the decades after he had finished his residency to use a type of medical device called a Lithotripter. There was three types Atul would mention.

  1. Shock-wave Lithotripter
  2. Electrohydraulic Lithotripter
  3. Laser Lithotripter

I did not do much research on the other two types, but it was shockwave lithotripters or what is known as extracorporeal shockwave lithotripsy that got me interested.

I know that all of these techniques are used to destroy or treat kidney stones or disorders with similar problems. The laser seems to focus just a strong intense beam of light to pulverize the kidney stone. I am not sure how the electrohydraulic lithotripters would work.

The way the shockwaves would work is that multiple beams of low intensity from various angles beam towards one spot inside the human body. When all the beams are focused on one exact area, the concentration of energy, like the plasma, can destroy tissue.

Here is my proposal. If I remember correctly, kidney stones have a composition which is primarily of a type of calcium crystal, calcium oxalate. The oxalate may not have the type of strength and toughness, or binding power, like the calcium phosphate or hydroxyapatite found in the cortical bone ECM, but I suspect that we can still break up tougher calcium deposits (ie the hydroapatites) and accumulations of calcium crystals if we increased the intensity of the multiple shockwaves coming from different directions.

When the shockwaves come together and focus on one area, they can cause micro-fractures in the cortical bone layer, which would mean that we have a chance to either pull the entire bone longer, or let the progenitor stem-like cells from the bone marrow and/or from the periosteum come along, and start to differentiate into the chondrogenic lineage.

Sky years ago talked about how if we can induce microfractures, then we might have a chance to pull the bones longer. Well, with this type of medical device, we will be able to induce micro-fractures at will and at whatever angle, or distance we wish for.

New LSJL study(but bone effects only)

The LSJL scientists Yokota and Zhang posted another LSJL related study.  Not a lot can be gathered in relation to LSJL on height growth unless Nfatc1 or ATF4 can be found to be chondrogenic inducers or to increase peak chondrocyte hypertrophy.

Evaluating treatment of osteoporosis using particle swarm on a bone remodelling mathematical model.

“The model formulated a temporal BMD change of a mouse’s whole skeleton in response to ovariectomy, mechanical loading[LSJL] and administration of salubrinal.”<-So even though this study is studying mainly BMD we can extrapolate other LSJL effects via LSJL’s affect on gene expression and cells.

“The best treatment was found to start with mechanical loading followed by salubrinal.”

“Ovariectomy (OVX) was modelled through oestrogen deprivation,
whereas salubrinal injection and knee loading were modelled by up-regulating p-eIF2α and inhibiting sclerostin, respectively.”<-In studying eif2a, it was unclear whether it could help increase height.

“To model the observed non-responsiveness to salubrinal at normal oestrogen levels in control mice, the model included a range of p-eIF2α values that does not elicit a change in ATF4 and NFATc1. When oestrogen levels decrease as in OVX mice, this range becomes
smaller, and ATF4 and NFATc1 become more responsive
to changes in p-eIF2α.”<-ATF4 has some involvement in height but it doesn’t seem to be a powerful effector like say CNP.

Loading BMD

This could connect to cartilage growth via NFATc1 or ATF4.  NFATc’s do affect chondrogenesis.

“Knee loading was applied using a custom piezoelectric loading platform in the lateral-medial direction 3 min/day at 15 Hz, with a
peak-to-peak force of 0.5 N”<-LSJL.  Mice were 12 weeks old at time of treatment.