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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