Thursday, April 21, 2011

Height Gaining by altering Bone Crystalization

Ozan Akkus from the university of Purdue where the Lateral Synovial Joint Loading modality was first developed, has an interesting theory of how bone changes with age.  Telomere length is one mechanism of how cells change with age but how does bone change with age and how do we revert it back to a more youthful and hopefully more chondrogenic state.

From Akkus:
  • type-B carbonate content significantly increases with age(so reducing Type-B carbonate may be a way to grow taller and result in height gaining)
  • the tissue composition gets more homogenous with age(less cartilage, hover the bone does begin as completely cartilage)
  • tissue heterogeneity is a correlate of tissue strength(We know that microcracks increase bone strength)
  • the crystallinity is a correlate of both fatigue and monotonic strength of bone.
Now, you might think that Type-B carbonate affects bone strength and not height.  However, it's bone heterogeneity that influences bone strength and the growth plates make the bone heterogeneous.  So therefore, Type-B carbonate may affect chondrogenesis in bone.

Effects of polyelectrolytic peptides on the quality of mineral crystals grown in vitro.

"Charged amino acids such as arginine, lysine, glutamic acid, and aspartic acid are abundant in noncollagenous proteins that regulate mineralization. Synthetic peptide forms of these amino acids affect crystal growth in precipitation of mineral crystals in solution{Remember that the mineralization does not necessarily stunt growth, if anything these amino acids will make you taller by increasing the mineralization growth when it does occur}. [Do] these peptides [affect] the viability and phenotype of bone marrow stromal cells (BMSCs){This will affect height growth as cartilage stem cell phenotypes make you taller} or on the in vitro mineralization process? Bone marrow was harvested from neonatal rat femora and cultured under conditions to induce mineralized nodule formation. Mineralized bone nodules were grown while supplementing the cultures with one of five polyelectrolytes: polystyrene sulfonate (PSS), poly-L: -glutamic acid (PLG), poly-L: -lysine (PLL), poly-L: -aspartic acid (PLA), and sodium citrate (SC), as well as a nontreated control group. The viability and the rate of collagen synthesis under the effect of these agents were characterized. [Analysis] was conducted on mineralized bone nodules to determine the effect of the polyelectrolytes on the mineralization, type-B carbonation, and crystallinity of the mineral phase. Morphology of resulting mineral crystals was investigated. PSS{Don't take polystyren sulfonate if you want to grow taller} had toxic effects on cells whereas the remaining agents were biocompatible, as the cell viability was either greater (PLG){Note that the Poly-L Glutamate is not compared with other forms of Glutamate so we can't be sure whether this form is superior, viability means larger cells and larger cells can make you taller} or not different from controls. The total collagen production by day 21 was 27% and 42% lower than controls for PLL{Lysine is needed but maybe the Lysine levels were too high} and PSS, respectively. Culture wells stained positively for alkaline phosphatase in the presence of polyelectrolytes, indicating that osteogenic differentiation was not impacted negatively. Type-B carbonation of the crystal lattice increased when treated with PLG, PLL, or PSS. Crystallinity of PLL and PSS was smaller than that of control. The mineral/matrix ratios of nodules did not change with polyelectrolyte treatment, with the exception of the PSS-treated group, which was less mineralized. XRD analysis of bone nodules indicated that PLA-treated samples were significantly longer{this is interesting, aspartame is used in artificial sweeteners, perhaps aspartame can make you taller?} than controls along the 002 direction{the 002 direction includes both length width and height}. The polypeptides consisting of charged amino acids are biocompatible and affect crystal quality and morphology in vitro in the presence of cells."

PLG increased the number of cells the most.  Since PSS was the least mineralized maybe it could be the most chondrogenic?  PSS had the highest levels of type-B carbonate.

So Aspartame may make you taller by increasing the size of bone nodules.  Glutamane may make you taller by increasing cell size.  Type-B carbonation may be a symptom rather than the cause of reduced chondrogenesis with age as this Type-B Carbonation is in itself caused by other things.

The compositional and physicochemical homogeneity of male femoral cortex increases after the sixth decade.

"The temporal and spatial fluctuations in the dynamics of secondary osteonal remodeling impart heterogeneity to the compositional quality of bone. Bone mineral density (BMD) fails to reflect this heterogeneity as being a single score. Specimens were prepared from mid-diaphyseal portions of human femora (age range 52-85 years old) and grouped based on the anatomical location (anterior, lateral, medial and posterior quadrants). Raman microscopy was used to obtain multiple measurements from each specimen which allowed the construction of histograms of mineralization, crystallinity and carbonation. Average mineralization of the medial quadrant and the data pooled over quadrants significantly increased with age{so bone mineralizaton continues to increase with age even post fusion}. The mean carbonation increased within the observed age range for the pooled data. The variations of values about the mean became tighter for mineralization, crystallinity and type-B carbonation with age, indicating an overall reduction in compositional heterogeneity of aging femoral cortex. Skewness values indicated that the distributions of histograms were not Gaussian. Age-related changes in mean tissue composition are confounded with changes in the variation of tissue make-up about the mean."

"bone tissue became more mineralized and more highly type-B carbonated with age"<-Note though that the youngest subjects were 52.

"The carbonate (CO32−) ion is distributed in three different locations in bone mineral. When a phosphate ion (PO43−) present in an apatite crystal is replaced by a carbonate ion (CO32−){The switch from a phosphate ion to a carbonate ion may affect the potential for chondrogenic differeniation}, the substitution is called type-B carbonate substitution, whereas carbonate ions occupying hydroxide ion (OH) sites are designated as type-A substitution. Unstable free carbonate ions loosely bound on the crystal surface are called labile carbonate."Calcium Phosphate has been shown to activate MMPs.  Those MMPs could affect height growth.  The MMPs helping to build cartilage canals to allow for height growth.

It may be more beneficial to grow taller by having weaker crystals as that can make it easier for the debinding of neighboring crystals from collagen.  This would increase collagen elasticity and stretched collagen would make you taller.

Visualization of a phantom post-yield deformation process in cortical bone.

"A prominent opacity is evident in the process zone of notched thin wafers of bone loaded in tension. Being recoverable upon unloading{thus loading without unloading may alter the bone hindering height growth but loading with a period of unloading will not}, this opaque zone can be stained only when the sample is under load, unlike the classically reported forms of damage which take up the stain in the unloaded state. Furthermore, despite the stain uptake, microcracks are absent in the stained area examined by high magnification optical microscopy and atomic force microscopy (AFM). Therefore, the size scale and the electric charge of the features involved in the process zone were probed at the submicron level by using a wide range of fluorescent dyes of different molecular weights and charges. Negatively charged dyes penetrate the process zone and that dyes greater than 10 kDa (about 10-20 nm in size) were unable to label the process zone. The opacity initiates at about 1% principal strain and the strain accumulates up to 14%. While the opacity was largely recoverable upon unloading, the core regions which experienced large strains had permanent residual strains up to 2%, indicating that the observed deformation phenomenon can be interlocked within bone matrix without the formation of microcracks{If you induce large enough strains you could grow up to 2% taller with no microcracks}. Based on the similarity of size and their known affinity for negatively charged species, exposure of mineral nanoplatelets is proposed as prime candidates. Therefore, the deformation process reported here may be associated with debonding of mineral crystals from the neighboring collagen molecules{so the electrical attraction of mineral crystals to collagen affects how easy it is to grow taller, this could affect the slow down of pubertal height growth as perhaps the bonding of mineral crystals to collagen discourages a chondrogenic phenotype}. Overall, post-yield deformation of bone at the micron scale takes place by large strain events which are accommodated in bone matrix by the generation of nanoscale positively charged interfaces."

To grow taller by tensile strain you need to generate strains large enough for residual strains.

"the peak strain values (11%) observed in our study might be stemming from deformations of collagen fibrils themselves, as opposed to fibrillar sliding"<-the collagen fibers may actually be increasing in length rather than just the sliding of fibers thus making bone taller and longer.

So, Type-B Carbonation(the switching from Phosphorus to Carbonate) may impact pubertal fusion by reducing MMP levels.  It also might affect growing taller by bone stretching by strengthening the attachment of crystals to collagen.

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