Grow Taller with cGKII?

Thanks to Alkoclar, the height increase forums are all the rage over CNP and reactivating growth plates.  CNP does not seem to able to reactivate growth plates but it does seem to increase chondrocyte hypertrophy which may lead to further height growth.  cGKII is a downstream target of CNP so when CNP increases so does cGKII and cGKII may inhibit Sox9 which is critical to height growth. However, things should be find as long as you have enough Sox9 to continue chondrogenesis.

cGKII deficiency results in dwarfism so a quantity of cGKII is needed for height growth.  cGKII works by inhibiting GSK-3Beta allowing for chondrocyte hypertrophy.  A gene involved with cGKII was found to be associated with human height.

Cyclic GMP-dependent protein kinase II is a molecular switch from proliferation to hypertrophic differentiation of chondrocytes.

"The Komeda miniature rat Ishikawa (KMI) is a naturally occurring mutant caused by an autosomal recessive mutation mri, which exhibits longitudinal growth retardation. The mri mutation [is] a deletion in the rat gene encoding cGMP-dependent protein kinase type II (cGKII). KMIs showed an expanded growth plate and impaired bone healing with abnormal accumulation of postmitotic but nonhypertrophic chondrocytes[which is what what'd expect given cGKII's role in chondrocyte hypertrophy]. Ex vivo culture of KMI chondrocytes reproduced the differentiation impairment, which was restored by introducing the adenovirus-mediated cGKII gene. The expression of Sox9, an inhibitory regulator of hypertrophic differentiation, persisted in the nuclei of postmitotic chondrocytes of the KMI growth plate. Transfection experiments in culture systems revealed that cGKII attenuated[reduced] the Sox9 functions to induce the chondrogenic differentiation and to inhibit the hypertrophic differentiation of chondrocytes[So cGKII inhibits Sox9 induced chondrogenesis of stem cells and encourages hypertrophic differentiation of chondrocytes]. This attenuation of Sox9 was due to the cGKII inhibition of nuclear entry of Sox9. The impaired differentiation of cultured KMI chondrocytes was restored by the silencing of Sox9 through RNA interference. cGKII [is] a molecular switch, coupling the cessation of proliferation and the start of hypertrophic differentiation of chondrocytes through attenuation of Sox9 function."

"cGKII is not involved in the two major signalings of chondrocyte hypertrophy: PTH/PTHrP and BMP"

" CNP neither reverses the impaired differentiation nor inhibits the Sox9 nuclear entry in cultured KMI chondrocytes"<-So CNP doesn't inhibit Sox9 without cGKII nor does CNP have an independent affect on chondrocyte hypertrophy.

Likely like most compounds you need an equilibrium quantity of Sox9.  Overexpression of Sox9 also causes dwarfism by inhibition of cyclin D1.

Regulation of fetal rat bone growth by C-type natriuretic peptide and cGMP.

"C-type natriuretic peptide (CNP) and its high affinity receptor-B are expressed in fetal bones. CNP accelerates longitudinal growth of fetal rat metatarsal bones in organ cultures.  CNP stimulates chondrocyte proliferation in the proliferative zone. CNP stimulates cell hypertrophy. CNP stimulates cartilage matrix production. Natriuretic peptide receptor-B contains an intracellular guanylyl cyclase catalytic domain. cyclic GMP (cGMP) [may] reproduce the effects of CNP on fetal bones. 8-Br-cGMP, like CNP, stimulates longitudinal growth and glycosaminoglycan synthesis.  unlike CNP, cGMP inhibits proliferation of growth plate chondrocytes and has no effect on hypertrophy. CNP stimulates longitudinal bone growth by increasing chondrocyte proliferation, chondrocyte hypertrophy, and cartilage matrix production. cGMP, a second messenger for CNP, reproduces some but not all of the effects of CNP."

So cGMP/cGKII cannot reproduce all the effects of CNP.

"Unlike atrial natriuretic peptide and BNP, which act as hormones inducing natriuresis and vasodilation, CNP is thought to act primarily as a paracrine factor regulating growth and differentiation in a variety of tissues"

"Natriuretic peptides interact with guanylyl cyclase-coupled natriuretic peptide receptors, NPR-A and NPR-B, leading to increased intracellular production of cGMP . Some of the effects of cGMP, in turn, are mediated by activation of two known protein kinases, cGMP-dependent protein kinase I and II"

"At the highest concentration, CNP increased the growth rate [of the rat fetal metatarsal bone] by 49% compared with the control group (122 ± 3 versus 82 ± 3 μm/day"

Growth increases most dramatically at the increase in concentration from 1nM of CNP to 10 nM.