Grow Taller by your periosteum?

I provide articles supporting Natural Height Growth's theory that periosteal stripping could help increase height.  When cartilage first condenses in the embryo there is no periosteum therefore the periosteum could serve as a mechanism to inhibit growth related to maturity.  Can rapid repetive loading(like via a chisel and hammer method) be akin to periosteal stripping?  One of the papers mentioned in the aforementioned page is on adult rats and seems to possibly have longitudinal bone growth.

We already know it's possible to grow taller by increasing the periosteal width of your certain bones that have periosteum oriented in the longitudinal direction such as the flat bone of the skull .  We also know that the periosteum is key in distraction osteogenesis surgery.  Tissue damage is highly anabolic.  How does muscular hypertrophy occur?  By damage to the myosin-actin bridge.  Does this damage just repair what was done before?  No it increases the size of your muscle according to the cellular signals as regulated by myostatin(testesterone inhibits myostatin) plus other factors.  Some of the cells that are released from damage to the muscle tissue go to repair but others go to build new muscle.

There are studies that show that bone can increase in size.  Tissue damage is highly anabolic and bones can increase in size, the periosteum is a tissue and has been shown to be highly important in limb lengthening surgery, therefore the periosteum is likely to have anabolic effects on your bone.  The periosteum contains progenitor cells which are like stem cells.

Even though the progenitor cells from the periosteum are not as potent as the stem cells from trabecular, it still has anabolic effects.  The periosteum also contains fibroblasts which are anabolic for connective tissues and what can possibly account for the increase in periosteal width in runners.

One problem is the location of the most easily accessible periosteum(in the tibia) which damage to the tissues should only increase bone width unless the periosteal progenitor cells somehow differentiate into chondrocytes.  Lateral Synovial Joint loading would definitely cause shear strain on the periosteum thus causing anabolic effects on the periosteum that way.  However, it's unclear whether LSJL would cause hydrostatic pressure in the periosteum as the periosteum is far more malleable than the hard tissue of the bone surrounding the bone marrow.

Here's an article about the direct effect of the periosteum on growth plate development:

Tissue engineering models of human digits: effect of periosteum on growth plate cartilage development.

"Tissue-engineered middle phalanx constructs of human digits were investigated to determine whether periosteum wrapped partly about model midshafts mediated cartilage growth plate formation. Models were fabricated by suturing ends of polymer midshafts in a human middle phalanx shape with polymer sheets seeded with heterogeneous chondrocyte populations from bovine articular cartilage. Half of each midshaft length was wrapped with bovine periosteum{if periosteum was wrapped on the midshaft ends would the bone than grow longer?}. Constructs were cultured, implanted in nude mice for up to 20 weeks, harvested and treated histologically to assess morphology and cartilage proteoglycans. After 20 weeks of implantation, chondrocyte-seeded sheets adjacent to periosteum-wrapped midshaft halves established cartilage growth plates resembling normal tissue in vivo. Sheets adjacent to midshafts without periosteum had disorganized cells and no plate formation. Proteoglycans were present at both midshaft ends. Periosteum appears to guide chondrocytes toward growth plate cartilage organization and tissue engineering provides means for carefully examining construct development of this tissue."

So the periosteum is needed to from growth plates.  Chondrocytes not near periosteum will not form growth plates and will not make you taller.  Adults have periosteum so this is a good sign for the potential for adult growth plates.  There is usually no periosteum surrounding the epiphysis of the bone which could make it difficult to form growth plates there as an adult.  But there is periosteum at the end of the epiphysis when it becomes the diaphysis, so it may be close enough to direct the formation of new growth plates.

"After 20 weeks of implantation, engineered human middle phalanx models were found to have glistening, firm and well defined cartilage on both ends of their individual midshaft regions. The portion of midshaft covered with periosteum consisted of essentially clear tissue having a few red-colored areas over its surface indicative of vascular formation. The midshaft region left unwrapped was notably reddened and vascularized{so the periosteum does not seem to have an effect on growth plate vascularization}. X-ray radiography revealed marked mineral deposition within the midshafts of the models only where periosteum had been placed and sutured. No mineral formation was detectable in the cartilage regions at the ends of the models.​"

So it could be the periosteum that affects the distinction between articular and growth plate cartilage.  The reason that articular cartilage usually does not ossify could be that it's too far away from periosteum.

"Over identical implantation times, chondrocyte-seeded PGA sheets adjacent to the half of the same model midshafts left uncovered by periosteum had disorganized cells and no growth plate formation or mineralization"<-So you need both chondrocytes and periosteum to grow taller.  And the chondrocytes need to be pretty close to the periosteum as the chondrocytes adjacent to the periosteum did not form growth plates.

"Periosteal tissue mediates growth plate cartilage formation, perhaps by synthesis and secretion of growth factors and other proteins that provide diffusion-limited regulation and control of neighboring cartilage."<-So we could mimic the benefits of periosteal tissue by increasing serum levels of growth factors and proteins.  It would be hard to mimic the diffusion regulation and control of neighboring cartilage.

Shear Strain from lateral synovial joint loading may help spread periosteal growth factors to the epiphysis.  Periosteum also has the ability to lengthen.

The fact that LSJL targets height growth by stimulating cell differentiation in the epiphysis into chondrocytes and that chondrocytes will not form growth plates unless adjacent to periosteum(and the epiphysis usually has no periosteum) means that it is likely that the periosteum has to be addressed to maximize gains from LSJL.

Here's the diagram of the study of the portions of the bone attached to periosteum:

Since the scientists attached the periosteum themselves it is likely that this does not completely represent a periosteal distribution pattern but you can see some periosteum at the very end of the epiphysis.  Any stem cells that differentiate into chondrocytes at this end zone could have sufficient access to periosteum.  Any other stem cells that differentiate in the remainder of the epiphysis will not form growth plates.  Since only a small portion of the epiphysis is covered by periosteum, this makes only a small portion of stem cells successfully differentiated by LSJL increase height.

This could explain LSJL stagnation as well.  In the beginning, individuals epiphysis may be well oriented to the periosteum making it easy for the chondrocytes to find surrounding periosteum.  However, growing taller changes the epiphysis and periosteum thus perhaps making it harder for chondrocytes to be located next to periosteum.

Also, it was noted that people who performed LSJL got a larger epiphysis.  It was then theorized that this could be due to chondrogenesis in the epiphysis.  This is now not possible as growth plates cannot form unless adjacent to periosteum.  The enlarged epiphysis is likely due to a direct increase in the width of individual osteons and direct bone deposition by osteoblasts.

There are two ingredients to growing taller:  Stem Cells differentiating into chondrocytes and those chondrocytes being adjacent to periosteum.  LSJL and some supplements that increase TGF-Beta1 and BMP-2 can help with the former, now we need to deal with the latter.

Here's a study that shows how the periosteum can cause bone regeneration:

A novel osteogenesis technique: The expansible guided bone regeneration

"Guided bone regeneration is a unique osteogenesis technique that requires a barrier membrane under periosteum to create space for bone regeneration{if we extend the periosteum over the longitudinal ends of the bones and create a barrier membrane then we can grow taller, also we can grow taller when periosteum is already at the longitudinal location of the bone such as the flat bone of the skull}. However, creating sizeable spaces is clinically not commonly feasible. A titanium plate and a thin silicone membrane were surgically layered on each calvaria of eight rabbits. Then, the periphery of the silicone membrane was fixed by a plastic ring to the underlying bone using titanium micro screws. After 1 week, a 5-mm-length titanium screw was used to elevate the titanium plate, which in turn elevated the silicone membrane together with overlying soft tissue in a rate of 1 mm/day for 5 days to create a secluded space. Animals were killed at 2 months (n = 4, group 1) and 4 months (n = 4, group 2) after the elevation. Histological and microradiographical analyses demonstrated creation of an amount of de novo bone formation (68.2 ± 22 mm3 in group 1 and 70.3 ± 14 mm3 in group 2) in the sizeable created spaces (207.1 ± 31 mm3 in group 1 and 202 ± 21 mm3 in group 2) without exposure of the device. This novel osteogenesis technique, “expansible guided bone regeneration,” created a substantial in vivo incubator without applying growth factors or osteoprogenitor cells. Creating a growing space over the secluded surface allowed the development of normal biological healing process occurring on the bone surface into a regenerative process, generating bone outside the genetically determined skeletal bone{so what we can do is create a growing space between the articular cartilage and the subchondral ends of bone}. This technique is a new tissue engineering approach stimulating endogenous tissue repair without applying cells or factors exogenously."

"large volumes of bone can be produced in a predictive manner without exogenously applying the three key players, if the space is provided by injecting biocompatible gel under periosteum."<-space plus periosteum equals bone growth.  The problem is there's no periosteum at the longitudinal ends of bones.

"More recently, we and others have been reported that gradual periosteum elevation creating a space over bone surface results in new bone formation in this space"<-How do we elevate and stretch the periosteum?

"the invasion of the created space with highly competitive nonosteogenic soft tissue and poor quality of the newly formed bone are the main drawbacks of this technique"

In the study they use an elevation screw to lift the periosteum.  Maybe we can mimic this with mechanical stimuli somehow.

"Upon activation of bone surface, biological healing process taking place on the activated surface is kept confined to the surface during the first week. After that the elevation plate is set to move upward, the membrane is gradually elevated and the space attains its maximum size in 5 days."

Now we we need find mechanical stimuli that can stretch periosteum over the longitudinal ends of bones and that can elevate the periosteum.

The nature and role of periosteum in bone and cartilage regeneration.

"[Can] periosteum from different bone sources in a donor [result] in the same formation of bone and cartilage? In this case, periosteum obtained from the cranium and mandible (examples of tissue supporting intramembranous ossification) and the radius and ilium (examples of tissues supporting endochondral ossification) of individual calves was used to produce tissue-engineered constructs that were implanted in nude mice and then retrieved after 10 and 20 weeks. Specimens were compared in terms of their osteogenic and chondrogenic potential by radiography, histology, and gene expression levels. By 10 weeks of implantation and more so by 20 weeks, constructs with cranial periosteum had developed to the greatest extent, followed in order by ilium, radius, and mandible periosteum. All constructs, particularly with cranial tissue although minimally with mandibular periosteum, had mineralized by 10 weeks on radiography and stained for proteoglycans with safranin-O red (cranial tissue most intensely and mandibular tissue least intensely). Gene expression of type I collagen, type II collagen, runx2, and bone sialoprotein (BSP) was detectable on QRT-PCR for all specimens at 10 and 20 weeks. By 20 weeks, the relative gene levels were: type I collagen, ilium >> radial ≥ cranial ≥ mandibular; type II collagen, radial > ilium > cranial ≥ mandibular; runx2, cranial >>> radial > mandibular ≥ ilium; and BSP, ilium ≥ radial > cranial > mandibular. The osteogenic and chondrogenic capacity of the various constructs is not identical and depends on the periosteal source regardless of intramembranous or endochondral ossification. Cranial and mandibular periosteal tissues appear to enhance bone formation most and least prominently, respectively."

Only the madible had no signs of cartilage proteoglycans.

"These results indicate that osteoblasts and chondrocytes derived from sutured periosteum remain viable during implantation and migrate into the constructs. The cells proliferate and secrete matrix that leads to new bone and mineral formation (osteoblasts) and new cartilage (chondrocytes) in interior spaces of the scaffolds as well as in the tissue over the scaffolds"<-With LSJL we have no scaffold.  We're trying to use endogenous tissues as a scaffold.

Multiple exostosis: a short study of abnormalities near the growth plate.

"The pathogenesis of multiple exostosis has been controversial with many theories put forward including the structural/mechanical theory, which emphasizes that the osteochondroma arises in the displaced growth plate cartilage penetrating a defective periosteum. Recently, molecular genetics has offered the neoplastic model with tumor suppressor genes implicated in the development and pathogenesis of exostosis. In this study, we demonstrated the spectrum of histological abnormalities in the developing exostosis present on the surface of the bone at the physis. Seven skeletally immature patients with multiple exostoses were used in this study. The patients' families were advised of and consented to the proposed study. Coincident with removal of symptomatic exostoses that was adjacent to the physis, a thin strip of bone with overlying periosteum was removed to include the edge of the physis. This was followed by formalin fixation and routine paraffin embedding. We demonstrated the earliest lesion as a microchondroma within the periosteum adjacent to the normal physis (also called the 'groove of Ranvier'). More mature progressively larger lesions showing enchondral ossification were seen distally. The periosteum and the perichondrium were intact with normal physis. Our observations give support to the fact that precursor cells in the periosteum adjacent to the physis (also called the 'groove of Ranvier') gives rise to the chondrocytes that clonally expands and develops into exostosis."

"the cause of exostoses was a ‘fault of the epiphyseal plate, nests of cartilage being misplaced’. He indicated that ‘fragments of cartilage around the epiphyseal line become isolated on the surface of the metaphysis, proliferate, and form exostosis’. ‘The periosteum, which is incomplete at the sites of these cartilaginous nests, fails to model the metaphysis in a normal manner’."

"Multiple noncontiguous clusters of cartilage cells of increasing size were found on the surface of the bone. The chondromas increased in size as the distance from the physis increases."

In vivo generation of cartilage from periosteum.

"Damaging the periosteum may be a way to generate ectopic cartilage or bone, which may be useful for the repair of articular cartilage and bone defects. Periosteum was bilaterally dissected from the proximal medial tibia of New Zealand White rabbits. Reactive periosteal tissue was harvested 10, 20, and 40 days postsurgery and analyzed for expression of collagen types I, II, and X, aggrecan, osteopontin, and osteonectin and collagen types I and II. Reactive tissue was present in 93% of cases. Histologically, this tissue consisted of hyaline cartilage at follow-up days 10 and 20. Expression of collagen type II and aggrecan was present at 10 and 20 days postsurgery. Highest expression was at 10 days. Expression of collagen type X increased up to 20 days. No significant changes in the mRNA expression of osteopontin or osteonectin were observed. Cartilage [was present], which was positive for collagen types I and II at 10 days and only for collagen type II at 20 days. At 20 days postsurgery the onset of bone formation was also observed. At 40 days postsurgery, the reactive tissue had almost completely turned into bone."

"cells in the cambial layer of the periosteum have chondrogenic potential in vitro and in vivo"

The ectopic cartilage is at the longitudinal ends of the bones so maybe it can increase height.

Regulation of endochondral cartilage growth in the developing avian limb: cooperative involvement of perichondrium and periosteum.

"To determine if the perichondrium and periosteum regulate growth through the production of diffusible factors, we have tested various conditioned media from these tissues for the ability to modify cartilage growth in tibiotarsal organ cultures from which these tissues have been removed. Both negative and positive regulatory activities were detected. Negative regulation was observed with conditioned medium from (1) cell cultures of the region bordering both the perichondrium and the periosteum, (2) co-cultures of perichondrial and periosteal cells, and (3) a mixture of conditioned media from perichondrial cell cultures and periosteal cell cultures. Positive regulation was observed with conditioned media from several cell types, with the most potent activity being from articular perichondrial cells and hypertrophic chondrocytes."

"At the point where the boney shaft borders the cartilage, the perichondrium (PC) differentiates into the periosteum (PO), whose cells have osteoblastic potential"

"PC/PO-free long bones [had an] increase in overall length of the cartilage [resulting from] increases in the sizes of both the proliferative and hypertrophic zones"

Multiple mechanisms of perichondrial regulation of cartilage growth.

"he perichondrium (PC) and the periosteum (PO) negatively regulate endochondral cartilage growth through secreted factors. Conditioned medium from cultures of PC and PO cells when mixed (PC/PO-conditioned medium) and tested on organ cultures of embryonic chicken tibiotarsi from which the PC and PO have been removed (PC/PO-free cultures) effect negative regulation of growth. Of potential importance, this regulation compensates precisely for removal of the PC and PO, thus mimicking the regulation effected by these tissues in vivo. We have now examined whether two known negative regulators of cartilage growth (retinoic acid [RA] and transforming growth factor-beta1 [TGF-beta1]) act in a manner consistent with this PC/PO-mediated regulation. The results suggest that RA and TGF-beta1, per se, are not the regulators in the PC/PO-conditioned medium. Instead, they show that these two factors each act in regulating cartilage growth through an additional, previously undescribed, negative regulatory mechanism(s) involving the perichondrium. When cultures of perichondrial cells (but not periosteal cells) are treated with either agent, they secrete secondary regulatory factors into their conditioned medium, the action of which is to effect precise negative regulation of cartilage growth when tested on the PC/PO-free organ cultures. This negative regulation through the perichondrium is the only activity detected with TGF-beta1. Whereas, RA shows additional regulation on the cartilage itself. However, this regulation by RA is not "precise" in that it produces abnormally shortened cartilages. Overall, the precise regulation of cartilage growth effected by the action of the perichondrial-derived factor(s) elicited from the perichondrial cells by treatment with either RA or TGF-beta1, when combined with our previous results showing similar--yet clearly different--"precise" regulation by the PC/PO-conditioned medium suggests the existence of multiple mechanisms involving the perichondrium, possibly interrelated or redundant, to ensure the proper growth of endochondral skeletal elements."

"RA has been reported to be both an inhibitor and promoter of cartilage development. In developing embryos of various species, both hypervitaminosis A and hypovitaminosis A greatly disturb the organization of the growth plate. In cell cultures, low doses (50 nM) of RA promote cartilage differentiation. However, in organ cultures, the addition of RA produces the opposite effect: a dose-dependent inhibition of longitudinal bone growth. This finding is due to decreases in both chondrocyte proliferation and hypertrophy"<-one difference between an organ culture and cell culture is the presence of the periosteum.

"RA treatment of the intact cultures produced a reduction in cartilage length from 3.77 mm for the controls to 2.96 mm for the RA-treated. This reduction of 0.81 mm is an even greater overcompensation than for the PC/PO-free cultures, suggesting that RA must have another mechanism of action in addition to that which acts directly on cartilage"

"TGF-β1 showed negative regulation only with the intact organ cultures—not with the PC/PO-free ones. When 10 ng/ml TGF-β1 was added to the intact cultures, the lengths of the cartilage was reduced to 3.48 mm for the treated vs. 3.81 mm for the controls. However, the PC/PO-free organ cultures showed no response to TGF-β1 treatment, with both treated and untreated cultures growing to 4.0 mm"

"FGF-2 acts solely on the cartilage, resulting in identical cartilage lengths between intact and PC/PO-free cultures when treated with FGF-2."

"one of the three nuclear RARs (RARβ) has been shown to be expressed at high levels in the perichondrium, as is RA itself; the remaining two RARs (RARα and RARγ) are expressed in cartilage."

Intracellular tension in periosteum/perichondrium cells regulates long bone growth.

"erichondrium/periosteum cells were cultured on substrates with different stiffness. The medium produced by these cultures was added to embryonic chick tibiotarsi from which perichondrium/periosteum was either stripped or left intact. After 3 culture days, long bone growth was proportionally related to the stiffness of the substrate on which perichondrium/periosteum cells were grown while they produced conditioned medium. A second set of experiments demonstrated that the effect occurred through expression of a growth-inhibiting factor, rather than through the reduction of a stimulatory factor. Finally, evidence for the importance of intracellular tension was obtained by showing that the inhibitory effect was abolished when perichondrium/periosteum cells were treated with cytochalasin D, which disrupts the actin microfilaments. Modulation of long bone growth occurs through release of soluble inhibitors by perichondrium/periosteum cells, and that the ability of cells to develop intracellular tension through their actin microfilaments is at the base of this mechano-regulated control pathway."

"periosteum [may regulate] growth via a direct mechanical feedback mechanism where pressure in growing cartilage, balanced by tension in the periosteum, [modulating] growth processes of chondrocytes. "

" after 3 days of culture, distal cartilage length was significantly longer in stripped versus intact tibiotarsi in non-conditioned medium and in conditioned medium obtained from periosteum/perichondrium cell cultures on 3, 14, 21, and 48 kPa stiff substrates. The difference in distal length between stripped and intact tibiotarsus decreased with increasing stiffness and was no longer significant on 80 kPa gels and on glass"<-Thus the stiffness of the periosteum may affect the height reduction.

"Both the variations in substrate stiffness and applying cytochalasin D in culture modulated the ability of periosteum cells to actively develop intracellular tension via their actin microfilament network."

Stripped periosteum cartilage was about 33% higher than intact periosteum.

You can see here that axial loading increases periosteal thickness(From Cortical and trabecular bone adaptation to incremental load magnitudes using the mouse tibial axial compression loading model). This serves to contrast LSJL images here where there is less visible periosteal thickness in the without drilling mice.  One reason for this difference could be that LSJL involves less force as in the axial loading study periosteal thickness increased with increasing force.  So less increase of periosteal thickness could be one possibility in why LSJL can increase height but why axial loading does not.  Which leads to the question of whether axial loading can increase height with periosteal stripping.

Periosteal topology creates an osteo-friendly microenvironment for progenitor cells

"The periosteum on the skeletal surface creates a unique micro-environment for cortical bone homeostasis. In our study, we observed the cells in the periosteum presented elongated spindle-like morphology within the aligned collagen fibers, which is in accordance with the differentiated osteoblasts lining on the cortical surface. We planted the bone marrow stromal cells(BMSCs), the regular shaped progenitor cells, on collagen-coated aligned fibers, presenting similar cell morphology as observed in the natural periosteum. The aligned collagen topology induced the elongation of BMSCs, which facilitated the osteogenic process. Transcriptome analysis suggested the aligned collagen induced the regular shaped cells to present part of the periosteum derived stromal cells(PDSCs) characteristics by showing close correlation of the two cell populations. In addition, the elevated expression of PDSCs markers in the cells grown on the aligned collagen-coated fibers further indicated the function of periosteal topology in manipulating cells’ behavior. Enrichment analysis revealed cell-extracellular matrix interaction was the major pathway initiating this process, which created an osteo-friendly micro-environment as well. At last, we found the aligned topology of collagen induced mechano-growth factor expression as the result of Igf1 alternative splicing, guiding the progenitor cells behavior and osteogenic process in the periosteum. This study uncovers the key role of the aligned topology of collagen in the periosteum and explains the mechanism in creating the periosteal micro-environment, which gives the inspiration for artificial periosteum design."

"The natural periosteum is a thin layer of connective tissue covers the outer surface of bone and connects to bone by strong collagenous fibers. The periosteum extends to the outer circumferential and interstitial lamellae of bone"

"collagen orientation in periosteum is aligned with preferential directions of tissue growth"