Increasing height with CamkII?

Camk2g is downregulated by LSJL.

Calcium/calmodulin-dependent protein kinase II activity regulates the proliferative potential of growth plate chondrocytes.

"The generation of differentiated cells to promote tissue growth is at odds with the requirement to maintain the stem cell/progenitor cell population to preserve future growth potential. In the growth plate cartilage, this balance is achieved in part by establishing a proliferative phase that amplifies the number of progenitor cells prior to terminal differentiation into hypertrophic chondrocytes. Endogenous calcium/calmodulin-dependent protein kinase II (CamkII, also known as Camk2) activity is upregulated prior to hypertrophy and loss of CamkII function substantially blocks the transition from proliferation to hypertrophy. Wnt signaling and Pthrp-induced phosphatase activity negatively regulate CamkII activity[So increasing Wnt signaling and PTHrp makes chondrocytes proliferate longer before hypertrophy]. Release of this repression results in activation of multiple effector pathways, including Runx2- and β-catenin-dependent pathways."

So this provides evidence that LSJL induces Wnt signaling.

"Prehypertrophic chondrocytes produce Ihh, which acts to promote chondrocyte proliferation and to induce Pthrp expression in resting chondrocytes. Pthrp secreted by resting chondrocytes antagonizes both Ihh function and the proliferative to prehypertrophic chondrocyte transition. Wnt5a and Wnt5b coordinately control the transitions from resting to proliferative and from proliferative to prehypertrophic chondrocyte."

"Ectopic activation of CamkII in proliferative chondrocytes upregulates endogenous CamkII activity and promotes Ihh expression"

"CamkII activity substitutes for Fzd signaling to stabilize β-catenin in prehypertrophic and hypertrophic chondrocytes."

"We examined the loss-of-function phenotype in chondrocytes homozygous for a Ctnnb1[codes for Beta-Catenin] conditional allele that carry a Col2a1::cre transgene. Mutant long bones were significantly shorter and showed reduced cell density compared with wild type. Mutant growth plate chondrocytes matured forming prehypertrophic and hypertrophic chondrocytes that have normal levels of pCamkII positive nuclei. Thus, β-catenin is not an essential regulator of CamkII activity. β-catenin [plays a minor role]in hypertrophy either downstream of or in parallel to CamkII function."

"Pthrp signaling is a dominant repressor of daCamkII function that acts by regulating the state of CamkII phosphorylation."

"pCamkII[phosphorylated-inactive] is highest in cells showing elevated nuclear β-catenin, an effector of canonical Wnt signaling."

"The range of action of secreted signaling molecules robustly defines the proliferative space, which, when cell size (proliferative chondrocytes are 7-8 μm tall) and cell packing (columns) are tightly regulated, limits the number of chondrocytes that can be generated from an individual progenitor cell in a unit of time. Restricting the number of cells generated, in turn, determines growth potential by limiting the number of cells available for hypertrophy. Displacement of the entire developing column from the source of Pthrp, as a result of continual recruitment of new mother row cells that initiate formation of new columns, establishes a time window for column formation that sets a limit on total cell amplification from a single progenitor cell. Precise regulation of CamkII activity by modulation of signaling pathway output could provide a mechanism for age-dependent and growth plate-dependent differences in growth rates of developing long bones."


Ca2+/Calmodulin-dependent kinase II signaling causes skeletal overgrowth and premature chondrocyte maturation.

"[In the chick], constitutive activation of Calcium/Calmodulin-dependent kinase II (CaMKII) in the developing wing resulted in elongation of skeletal elements associated with premature differentiation of chondrocytes. The premature maturation of chondrocytes was a cell-autonomous effect of constitutive CaMKII signaling associated with down-regulation of cell-cycle regulators and up-regulation of chondrocyte maturation markers. In contrast, the elongation of the skeletal elements resulted from a non-cell autonomous up-regulation of the Indian hedgehog responsive gene encoding Parathyroid-hormone-related peptide. Reduction of endogenous CaMKII activity by overexpressing an inhibitory peptide resulted in shortening of the skeletal elements associated with a delay in chondrocyte maturation."

"PPR signals via heterotrimeric G-proteins such as Gs, which stimulates adenylyl cyclase or Gq/11, which activates phospholipase C (PLC), thereby generating multiple second messengers. Gs signaling leads to activation of cAMP-dependent protein kinase A (PKA) and is required to keep chondrocytes in the proliferative pool. In contrast, PPR signaling via Gq/11 and PLC stimulates chondrocyte maturation"

"Cells ectopically expressing Ihh always colocalized with daCaMKII expressing cells and cells ectopically expressing ColX also colocalize with daCaMKII positive cells"

" Expression of c-Fos and c-Jun, which are ubiquitously expressed in proliferating chondrocytes of wild-type skeletal elements, was down-regulated in daCaMKII infected cells, while their expression was not affected by kdCaMKII misexpression "

This study is rich with information so I'll have to review it later.