Height Increase Pages

Thursday, July 26, 2012

Grow Taller by Inhibiting GSK3Beta?

GSK3Beta is inhibited by phosphorylating it. Lithium inhibits GSK3Beta.  cGKII from the NO or CNP pathway can inhibit GSK3Beta.  Serotonin inhibits GSK3Beta.  GSK3Beta degrades Beta-Catenin.  Insufficient Beta-Catenin results in dwarfism.

Deletion of glycogen synthase kinase-3β in cartilage results in up-regulation of glycogen synthase kinase-3α protein expression.

"Glycogen synthase kinase-3 (GSK-3) is a negative regulator of several signaling pathways that govern bone growth, such as insulin/IGF and Wnt/β-catenin. The two GSK-3 proteins, GSK-3α and GSK-3β, display both overlapping and distinct roles in different tissues. Pharmacological inhibition of GSK-3 signaling in a mouse tibia organ culture system results in enhanced bone growth[i.e. growing taller], accompanied by increased proliferation of growth plate chondrocytes and faster turnover of hypertrophic cartilage to bone. GSK-3 inhibition rescues some effects of phosphatidylinositide 3-kinase inhibition in this system, in agreement with the antagonistic role of these two kinases in response to signals such as IGF. Cartilage-specific deletion of the Gsk3b gene in mice has minimal effects on skeletal growth or development. Compensatory up-regulation of GSK-3α protein levels in cartilage is the likely cause for this lack of effect."

"GSK-3α and GSK-3β [have both overlapping and distinct roles]"

"Tibia treated with [an inhibitor that inhibits both GSK3alpha and Beta] grew 31% more than controls over the 6 d of organ culture"

"Inhibition of GSK-3 promotes long bone longitudinal growth by increasing bone formation."<-But is this only growth rate or adult height?

"GSK-3α, which is more widely expressed in the growth plate, is the predominate GSK-3 form targeted by inhibition of the PI3K pathway through the resting and proliferating zones, whereas GSK-3β is the main target in the prehypertrophic zone."

"The effect of the PI3K inhibitor was partially recovered by the combination with the GSK-3 inhibitor"<-Meaning some of the benefits of the PI3K pathway on height growth are mediated by it's inhibition of GSK-3.

"The cyclin-dependent kinase inhibitor p57 is both a marker of prehypertrophic chondrocytes and promotes cell cycle exit in the growth plate. In tibia organ culture, inhibition of GSK-3 or dual treatments of GSK-3 and PI3K inhibitors greatly increased the zone of p57 protein expression in the prehypertrophic zone"

"up-regulation of GSK-3α compensates for the loss of GSK-3β in cartilage."<-So we have to inhibit GSK-3alpha in addition to GSK-3Beta.

According to Inhibition of GSK3 by lithium, from single molecules to signaling networks., Lithium inhibits both forms of GSK3.  I'm not sure about the NO/CNP pathway or serotonin.  It's very likely that they do inhibit both.

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