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.”

The 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.