Breakthrough: Another study shows mechanical loads can alter height growth

Previously, I wrote another study about how mechanical loading can shape and alter joint and growth plate development.

If mechanical loading can alter limb development, then not only can mechanical loading regimes be used to increase height during development but also possible after growth plate fusion by creating new growth plates.  In fact one of the genes associated with the pre-growth plate cells in the zone of Ranvier is the mechanically sensitive to activation CMF608.

Mechanoadaptation of developing limbs: shaking a leg.

“The developing skeleton experiences mechanical loading as a result of embryonic muscle contraction. Embryos [may] coordinate the appearance of skeletal design with their expanding range of movements. Embryo movement [has a large role] in normal skeletal development; stage-specific in ovo immobilisation of embryonic chicks results in joint contractures and a reduction in longitudinal bone growth in the limbs. Epigenetic mechanisms allow for selective activation of genes in response to environmental signals, resulting in the production of phenotypic complexity in morphogenesis; mechanical loading of bone during movement appears to be one such signal. It may be that ‘mechanosensitive’ genes under regulation of mechanical input adjust proportionality along the bone’s proximo-distal axis, introducing a level of phenotypic plasticity{in other words it’s possible to alter how tall you will grow via mechanical factors}. If this hypothesis is upheld, species with more elongated distal limb elements will have a greater dependence on mechanical input for the differences in their growth, and mechanosensitive bone growth in the embryo may have evolved as an additional source of phenotypic diversity during skeletal development.”

“Cell movement-generated forces influence condensation of cartilage elements in developing limbs. There is also evidence that fundamental processes, including growth, differentiation, death and directional motility of cells, are likely guided by forces exerted by the cell cytoskeleton. This conforms with ‘tensegrity’ principles, with differential growth patterns producing local extracellular matrix distortion and the generation of tension in the cytoskeleton of associated cells.”<-LSJL would induce local extracellular matrix distortion and generate tension in the cytoskeleton of cells.

“dynamic loading in adult bones produces extracellular fluid flow within the bone’s lacunar-cannalicular system, which is detected by osteocytes”<-The idea is that LSJL goes further to induce MSCs to differentiate into growth plate plate chondrocytes.

“Embryonic muscle contraction appears to be necessary for the formation of bone ridges, which act as anchoring points for muscle attachment and are therefore important in the transduction of muscle-induced loading via tendons to the skeleton.”

“immobilisation of embryonic chicks alters cellular organisation of the interzone and results in changes in shape of the distal femur and proximal epiphysis of the tibiotarsus and fibula. After cavitation occurs, maintenance of joint cavities is also dependent on mechanical input. Post-cavitation induction of flaccid paralysis with pancuronium bromide, a non-depolarising neuromuscular blocker, also leads to loss of the joint cavities. Rigid paralysis induced with DMB, a depolarising neuromuscular blocking agent, causes muscle contraction and has been shown to partially maintain joint cavities “<-But there is there just a threshold of mechanical loading that is needed for proper development or can we enhance this development with enhanced mechanical loading.

“Detailed ‘targeting’ of specific temporal windows during development indicates that the effects of in ovo paralysis on bone length become significant at approximately E13 of development. This indicates that embryo bone growth is initially not sensitive to mechanical stimulus, but that mechanosensitivity is acquired later during development. This suggests that intrinsically regulated initial limb growth ‘switches’ later to regulation dominated by extrinsic factors such as mechanical signals. It remains to be determined whether this immobilisation-related skeletal growth retardation is due to deficient chondrocyte proliferation, differentiation, matrix synthesis or hypertrophy or due to insufficient replacement of calcified cartilage by bone during the endochondral ossification process. It has been suggested that mechanical loading regulates the elongation of chondrocyte columns during zebrafish craniofacial development”

evidence for mechanosensitivity in skeletal development is provided by observations of increased limb bone length when the level of embryo motility is increased in chicks. Incubation temperature increases embryo movement, with a 1 °C increase in incubation temperature producing a significant increase in embryo motility. This is associated with an increase in the number of myonuclei in embryo limb muscles and increased limb element lengths“<-Now this is the kind of fact we’re looking for.  So people can make their kids taller but what about us.  But we’d have to find the equilibrium temperature.

“This increase in limb length with temperature did not become significant until E12.5, providing further evidence that mechanosensitivity in skeletal element growth is acquired at a relatively late stage of development. Treatment with 4-aminopyridine (4-AP), a drug which stimulates the release of acetylcholine, thereby increasing its availability at the synaptic cleft and resulting in skeletal muscle hyperactivity, also stimulates embryo movement. Increases in tibia and femur lengths have been reported in chick embryos treated with 4-AP at E15 and E16, but not E14 ”

” The expression of IHH and hypertrophic markers such as MMP13 have been shown to be regulated in chondrocytes in vitro by cyclic mechanical stress”<-Although these genes wouldn’t be able to form new growth plates except possible IHH.  Mesenchymal Stem Cells transfected by IHH were induced to become chondrocytes in one study.

“In ovo immobilisation has been shown to alter expression patterns of COL X and IHH in embryonic limbs, suggesting that these genes are involved in linking mechanical stimuli from embryonic muscle contraction with regulation of bone formation in the limbs”

Unfortunately, this study only shows examples where longitudinal bone growth was altered in a very small window during embryonic development.  But increases the amount of evidence provided that mechanical loading can alter longitudinal bone growth which will eventually lead to prove that a specific mechanical loading regime such as that of LSJL may induce mesenchymal stem cells to become growth plate chondrocyte pre-cursors and form micro-growth plates.

Leave a Reply

Your email address will not be published. Required fields are marked *