There is a stretching apparatus promoted by Pravilo USA that may potentially work to induce articular cartilage endochondral ossification on height affecting joints.
I have stated in the past that the rack apparatus(and sleep stretching) is not likely to work to make you grow taller. First the load is not really on the bones or the articular cartilage. Second the load is not dynamic which has been to shown to be a key mechanism by which the bite jumping appliance in dentistry serves to induce articular cartilage endochondral ossification. Like dynamic movement is important to the bone(because of bones fluid contents and dynamic movement moves the fluid contents around) to stimulate growth, dynamic movement is important to the cartilage and the cells to stimulate the structure of the cells via fluid forces. Ultimately, a lot of the load is going to be on the tendons and ligaments but just be the constant moving around some of the load is surely going to applied to the articular cartilage.
I do not believe the load is going to be in such a way as to stimulate the bone directly(mostly via the enthesis and the articular cartilage). I do not think that applying load in a tensile fashion is necessary to stimulate the bone via torsional force. Torsion will stimulate the fluid contents of bone regardless of whether the torsion is applied in a compressive or tensile fashion.
I do however think this apparatus has possible potential in which to prove articular cartilage endochondral ossification. However, ACEO(articular cartilage endochondral ossification) is very slow so we’d need actual studies and actual going to the gym here and using the device is cumbersome. If we can prove that ACEO work then we can create easier to use devices.
Here’s an example of how Pravilo training apparatus can induce dynamic loading on the articular cartilage:
The twisting of the body is what makes it dynamic.
At about the one minute mark is where you can see the twisting applied:
In the store on the website there is parts to construct your own apparatus. I’m not sure if it’s worth it as ACEO is very slow. It’d be more for proof of concept. However, it could potentially work for your spine and there is no surgical mechanism that increases spinal height.
With my latest focus on research and experimentation of torsion leading potential bone overgrowth(new longitudinal bone growth). I did some research on scoliosis as in scoliosis there is a lot of research on the spine. Therefore, if torsion could stimulate longitudinal bone growth we’d expect to see overgrowth of the spinal column. It may still be possible however that even if scoliosis did not increase longitudinal bone growth that torsion may still increase longitudinal bone growth as scoliosis may not meet the dynamic threshold over which torsion stimulates longitudinal bone growth. However, I think the papers do suggest that scoliosis causes bone overgrowth.
“High-resolution computed tomographic scans of 77 patients with severe adolescent idiopathic scoliosis were included. Torsion and anterior-posterior and right-left asymmetry of each individual vertebral body and intervertebral disc were studied from T2 to L5, using semiautomatic analysis software. True transverse sections were reconstructed along the anterior-posterior and right-left axis of all endplates. These “endplate-vectors” were calculated semiautomatically, taking rotation and tilt into account. Torsion was defined as the difference in axial rotation between 2 subsequent endplates. Asymmetry was defined as the relative anterior-posterior or right-left height difference of the discs and the vertebrae.”
“There were at least 3 times more torsion, anterior overgrowth, and coronal wedging in the discs than in the vertebrae in the thoracic as well as in the (thoraco) lumbar curves (P < 0.001). These values correlated significantly with the Cobb angle (r ≥ 0.37; P < 0.001). Anterior overgrowth and coronal asymmetry were greater in the apical regions whereas torsion was most pronounced in the transitional segments between the curves.”<-just because torsion is more pronounced in certain segments does not mean that other segments did not undergo torsion overall.
“The discs contribute more to 3-D deformity than the bony structures, and there is significant regional variability. This suggests an adaptive rather than an active phenomenon.”<-the adaptative phenomenon could be torsion.
“On conventional 2-dimensional radiographs, it was observed that the discs were more wedge-shaped than the vertebral bodies in mild scoliotic curves whereas the wedging of the discs and vertebrae became more or less equal in more severe scolioses. These findings suggest that AIS[adolescent idiophatic scoliosisi] is primarily a deformation of the discs and that, according to Hueter-Volkmann’s law[compressed growth plates grow less, stretched growth plates grow more], the deformation of the vertebral bodies is secondary. However, at the same time, others reported increased coronal wedge angles of the vertebral bodies already in mild AIS, indicating abnormal vertebral growth.”
“Torsion per centimeter height: This was defined as the angle between the anterior-posterior axis of the superior endplate and the anterior-posterior axis of the inferior one of the same vertebra or disc in the axial plane divided by the height in centimeters. For example, if we found 3 vertebrae with a total height of 6.0 cm and a total torsion of 15°, torsion was 2.5°/cm.”
“In the thoracic curves, torsion was significantly greater in the IVDs than that in the vertebral bodies (6.2 ± 2.3°/cm height vs. 1.9 ± 0.7°/cm height, respectively; P < 0.001). In the (thoraco) lumbar curves as well, torsion of the IVDs was greater than vertebral torsion: 4.1 ± 2.6°/cm versus 1.2 ± 0.4°/cm; P < 0.001. In the apical as well as transitional levels of the thoracic curves, significantly more torsion was found in the discs than in the vertebral bodies (apex, respectively, 6.0 ± 2.4°/cm vs. 1.8 ± 0.9°/cm; transitional region, 6.3 ± 3.1°/cm vs. 2.1 ± 0.9°/cm; P < 0.001). In addition, a trend was observed that torsion was more pronounced in the transitional levels than around the apex[apex is the peak of the curve]; however, this did not reach statistical significance. In the different regions of the (thoraco) lumbar curves, we also observed that the discs were significantly more affected by torsion than the vertebral bodies: apical region, 3.8 ± 2.5°/cm torsion in the disc versus 0.9 ± 0.4°/cm in the vertebrae; transitional region, 4.7 ± 3.2°/cm versus 1.5 ± 0.8°/cm, respectively (P < 0.001). Again, a trend was observed that torsion was more pronounced in the transitional, nonapical levels of the curvature. In the (thoraco) lumbar curves, this trend became statistically significant (P ≤ 0.001).”So torsion is correlated with length difference but the degree of torsion does not directly correlate with the difference but there could be different factors than just the degree of torsion like how dynamically the torsion is applied.
” all individual AIS curves were longer anteriorly than posteriorly and rotated both between and within vertebrae in the axial plane. This rotated lordosis has been described by a number of authors, leading to the hypothesis that lordosis is the initiating deformity, and that scoliosis is the result of a disturbed anterior versus posterior growth process”
“anterior “overgrowth” of the discs versus vertebrae in the sagittal plane”
“These findings support that AIS is mainly a 3-D deformity of the discs, suggesting that abnormal vertebral growth is, according to Hueter-Volkmann’s law, rather a consequence than a cause of the deformity”
“scoliosis as a rotatory instability of the spine, and the development of AIS depends on disturbance of the delicate balance between rotational stiffness of the spine on the one hand and rotation-inducing forces on the other. Once the spine decompensates into rotation around the stiff posteriorly located ligamentous axis, the vertebral bodies swing farther away from the midline than the posterior structures. At that point by definition, a lordosis starts to develop, leading to greater anterior length of the spine.”
“In conclusion, the IVDs contribute more to the 3-D deformity in AIS than the vertebral bodies. Because the processes of torsional deformation, anterior overgrowth, and coronal wedging are greater in the discs than in the vertebral bodies and are uniform in primary as well as compensatory AIS curves, it seems more logical that these morphological modifications are rather a consequence (among others through Hueter-Volkmann’s law) than a cause of the deformity.”<-so this suggests that torsion could potentially cause overgrowth.
Since scoliosis can be altered through exercise as suggested by studies such as Scoliosis-Specific exercises can reduce the progression of severe curves in adult idiopathic scoliosis: a long-term cohort study, this suggests that mechanical loading via exercise can alter the discs and vertebral bodies in the same way that scoliosis alters the mechanical loading of discs and vertebral bodies and alters their shape. IN the paper it suggests that the reduction may be due to “concave ligament stretching.” The authors of this study refuse to indulge the possibility that the change may be due to reduction in bon
“. The differential growth between the anterior and the posterior elements of each thoracic vertebra in the patients with AIS was significantly different from that in the controls (p < 0.01). There was also a significant positive correlation between the scoliosis severity score and the ratio of differential growth between the anterior and posterior columns for each thoracic vertebra (p < 0.01). Compared with age-matched controls, the longitudinal growth of the vertebral bodies in patients with AISis disproportionate and faster and mainly occurs by endochondral ossification. In contrast, the circumferential growth by membranous ossification is slower in both the vertebral bodies and pedicles”<-the faster growth could be due to mechanical stimulation by torsion.
“Relative anterior spinal overgrowth in AIS has been reported in morphological studies”
Here’s what’s meant by anterior:
“
The longitudinal growth of the anterior column occurs at the growth plates by endochondral ossification and continues until the girl is between 16 and 18 years of age. In contrast, endochondral ossification of the posterior elements is complete by the end of the first decade of life”
“The posterior elements subsequently only grow circumferentially by membranous ossification. We speculated that the pathomechanism of the disproportionate spinal growth in AIS might be a loss of coupling between endochondral and membranous ossification during adolescence.”
“the relatively shorter posterior column acts as a tether which hinders the lengthening of the anterior column during the period of rapid growth, forcing the spine to bend and rotate. Different tissues such as bone, spinal cord, ligaments, and muscles are included in the posterior column. The issue is which structure in the posterior column causes the tethering.”
“Tethering of the posterior soft tissues such as the posterior ligaments has been presumed to be the force acting on the spine to create the complicated deformity”<-I have seen other people theorize that the ligaments constrain longitudinal bone growth.
“There is much indirect evidence supporting the hypothesis that uncoupled endochondral-membranous bone formation causes the relative anterior spinal overgrowth in AIS. It is well known that girls with AIS have a tendency to be taller and thinner than their peers.”<-it is also possible that the scoliosis causes the overgrowth itself via torsional mechanical loading.
so this study suggests an alternative mechanism than torsion to cause the overgrowth but it does not rule out the torsion.
The implication of this study I think is that CRISPR or other gene therapy technology could potentially be used to elevate Chondromodulin levels to either quicken limb lengthening surgery or maybe induce ectopic cartilage formation?
“Chondromodulin (Cnmd) is a glycoprotein known to stimulate chondrocyte growth. We examined in this study the expression and functional role of Cnmd during distraction osteogenesis that is modulated by mechanical forces. The right tibiae of the mice were separated by osteotomy and subjected to slow progressive distraction using an external fixator. In situ hybridization and immunohistochemical analyses of the lengthened segment revealed that Cnmd mRNA and its protein in wild-type mice were localized in the cartilage callus, which was initially generated in the lag phase and was lengthened gradually during the distraction phase. In Cnmd null (Cnmd−/−) mice, less cartilage callus was observed, and the distraction gap was filled by fibrous tissues. Additionally, radiological and histological investigations demonstrated delayed bone consolidation and remodeling of the lengthened segment in Cnmd−/− mice. Eventually, Cnmd deficiency caused a one-week delay in the peak expression of VEGF, MMP2, and MMP9 genes and the subsequent angiogenesis and osteoclastogenesis. We conclude that Cnmd is necessary for cartilage callus distraction.“
So CNMD gene therapy could potentially be used to treat non-unions in limb lengthening surgery too.
“Cnmd−/− mice did not show abnormalities in cartilage development or endochondral bone formation during embryogenesis or normal growth, and further did not affect natural articular cartilage development. Thus, Cnmd functions as a chondrocyte modulator in specific conditions, causing osteogenesis such as cartilage or bone injury, but not in normal cartilage development and growth.”
“the relationship between mechanical stress and Cnmd in the process of cartilage callus formation during bone repair/regeneration.”<-Perhaps we could induce Cnmd via other mechanical stress mechanisms?
“We focused on distraction osteogenesis, which involves an osteotomy followed by a slow progressive distraction to lengthen congenitally or traumatically shortened extremities”
“Cnmd could directly stimulate chondrocyte proliferation and proteoglycan synthesis in vitro“
“Cnmd is required for cartilage callus formation due to tensile stress on the periosteum and is less involved in it due to hydrostatic pressure between the gaps”<-we can induce hydrostatic pressure and tensile stress via other mechanisms.
” the gap tissue is subject to approximately 15% deformation (compression and tension) during walking in a rabbit tibial lengthening model, indicating that compression as well as tensile forces act on the gap tissue during the distraction phase”
” the fibula spontaneously fractured during the distraction phase and lengthened in the same manner as the tibia.”
“increased expression of Tnmd mRNA in Cnmd−/− mice at the distraction phase. Tnmd is a type II transmembrane protein that shares a cysteine-rich domain with Cnmd at the C-terminus”<-we actually want Tnmd to increase as Tendons are one of the limiting factors in the amount of growth you can get in limb lengthening surgery.
“Tnmd mRNA expression was strongly upregulated by 5% axial cyclic strain in tendon stem/progenitor cells”
“elongation of cartilage callus during distraction osteogenesis was suppressed in Cnmd−/− mice and subsequent bone formation and remodeling slowed and partially failed. The study results indicate that Cnmd-mediated cartilage callus elongation is necessary for distraction osteogenesis and Cnmd could be a mechanical response chondrogenic factor. New insights into the function of Cnmd may establish this molecule as a candidate therapeutic agent for successful bone healing.”
Yam-derived exosome-like nanovesicles stimulate osteoblast formation and prevent osteoporosis in mice
“Plants-releasing exosome-like nanovesicles (PENs) contain miRNA, bioactive lipids, mRNAs, and proteins to exert antioxidant, anti-inflammatory, and regenerative activity. Substances extracted from yams have been reported to promote osteoblast growth in bone regeneration, which prevent weak and brittle bones in osteoporosis. Herein, we describe the beneficial effects of yam-derived exosome-like nanovesicles (YNVs) on promoting differentiation and mineralization of osteoblasts for bone regeneration in ovariectomized (OVX)-induced osteoporotic mice. YNVs were successfully isolated and characterized. YNVs stimulate the proliferation, differentiation, and mineralization of osteoblasts with increased bone differentiation markers (OPN, ALP, and COLI). Interestingly, YNVs do not contain saponins including diosgenin and dioscin known to mainly exert osteogenic activity of yams. Instead, the osteogenic activity of YNVs was revealed to be resulted from activation of the BMP-2/p-p38-dependent Runx2 pathway{and BMP2 can stimulate longitudinal bone growth}. As a result, YNVs promote longitudinal bone growth and mineral density of the tibia in the OVX-induced osteoporotic mice in vivo, and these results positively correlate the significant increases in osteoblast-related parameters. In addition, the orally administered YNVs were transported through the GI tract and absorbed through the small intestine. These results showed an excellent systemic biosafety determined by histological analysis and liver/kidney toxicity tests. Taken together, YNVs can serve as a safe and orally effective agent in the treatment of osteoporosis{and possibly growing taller pre-skeletal maturity}.”
Looking at slide 3 the Yam group looks significantly longer.
“Plants release exosome-like nanovesicles (PENs) containing miRNA, bioactive lipids, mRNAs, and proteins into their extracellular spaces, and these PENs serve as extracellular messengers that stimulate cell-cell communication and biological defense against pathological diseases. Recently, PENs have been widely explored as a drug delivery system in various therapeutics by isolating diverse plant sources including starchy roots and tubers, nuts and seeds, as well as fresh and dried plants”
“safe, biocompatible, and biodegradable without any negative effects on intestinal barrier function or other organ toxicities, but can also be prepared in large amounts.”
I couldn’t get this full study to check how significantly it influenced longitudinal bone growth.
The next study suggests that mechanisms that inhibit SPIN4 whether via gene therapy or supplements etc may be a way to enhance longitudinal bone growth. The next study is also by Jeffrey Baron who is huge in growth research.
A new genetic cause of overgrowth syndrome
“Pathogenic genetic variants in epigenetic regulatory proteins can cause overgrowth syndromes, such as Sotos syndrome due to mutations in NSD1 or Weaver syndrome due to mutations in EZH2. The identified genes encode DNA or histone methyltransferases, primarily serving as epigenetic writers. However, no overgrowth disorder has previously been described in a gene that acts primarily as an epigenetic reader{epigenetics are involved in delaying growth plate senescence so epigenetic alterations may keep growth plates open for longer}. We studied a 13-year-old male patient with generalized overgrowth of prenatal onset. His birth weight and length were 5.85 kg (+4.3 SDS) and 62 cm (+4.8 SDS), respectively. His height growth was striking at > +4 SDS without a significantly advanced bone age, eventually requiring epiphysiodesis at age 13 to reduce his adult height{I don’t know why they would do this with all the advantages of tall stature}. His timing of puberty was as expected. His biochemical studies, including IGF-1, were all negative. Karyotype, mutation analysis in NSD1 for Sotos syndrome, and chromosome 11p15 analysis (MLPA and methylation) for Beckwith-Wiedemann syndrome were normal. Furthermore, he had normal development and intelligence. His mother and maternal grandmother showed a significant height gain (+2 SDS gain) compared to their midparental height, suggesting an X-linked semi-dominant inheritance. Exome sequencing on the extended family identified a frameshift variant (NM_001012968.3, c.312_313AGdel) in Spindlin 4 (SPIN4), one of the epigenetic readers, with X-linked inheritance. Neither this variant nor any other loss-of-function variant in SPIN4 was present in a population database (gnomAD). In functional studies, we found evidence that SPIN4 binds specific histone modifications, promotes canonical WNT signaling, inhibits cell proliferation in vitro, and that the identified frameshift variant had lost all of these functions.Ablation of Spin4 in mice (either male or female) recapitulated the human phenotype with generalized overgrowth, including increased longitudinal bone growth{so SPIN4 inhibitors during development may stimulate longitudinal bone growth?}. Growth plate analysis revealed increased cell proliferation in the proliferative zone and an increased number of progenitor chondrocytes in the resting zone. We also found evidence of decreased canonical Wnt signaling in growth plate chondrocytes, providing a potential explanation for the increased number of resting zone chondrocytes. In conclusion, our findings provide strong evidence that SPIN4 is an epigenetic reader that negatively regulates mammalian body growth and that loss of SPIN4 causes an overgrowth syndrome in humans, expanding our knowledge of the epigenetic regulation of human growth.”
I can’t get this fully study yet but I will keep trying.
There’s not a lot of data on SPIN4 so this is really a novel finding. I also can’t find any research on compounds other than antibodies that inhibit SPIN4.
I tried not to information dump as much this time but I did last. So I didn’t press him enough on the Kleinburg paper. I also haven’t really explained fluid flow theory so I will have to do a video on that.
I touched on everything I wanted to touch(obviously not in as much detail) in but I wanted to add that one advantage that an exercise based routine would have over the surgery is that it would provide potentially daily stimulation to bones and could have anti-aging effect as bones are reservoir of stem cells for other tissues.
