Increasing Height with Proepithelin?

The NF-kappaB pathway isn't typically associated with height growth. The only anabolic gene immediately associated with anabolic activity that's associated with NF-kappaB is PI3K. However, propethelin may stimulate growth plate chondrogenesis by means of the NFkappa-B pathway therefore exploring the NFkappa-B pathway may have other height increase applications.

Proepithelin Stimulates Growth Plate Chondrogenesis via Nuclear Factor- B-p65-dependent Mechanisms

"Proepithelin [is] an important regulator for cartilage formation and function. Proepithelin [mediates] induction of cell proliferation, differentiation, and apoptosis in the metatarsal growth plate. Proepithelin-mediated stimulation of metatarsal growth and growth plate chondrogenesis was neutralized by pyrrolidine dithiocarbamate, a known NF-κB inhibitor{propethelin stimulated growth plate chondrogenesis and therefore height growth, since propethelin's effects are mediated through NF-kappaB, NF-kappaB may be important for height growth as well}. In rat growth plate chondrocytes, proepithelin induced NF-κB-p65 nuclear translocation, and nuclear NF-κB-p65 initiated its target gene cyclin D1 to regulate chondrocyte functions. The inhibition of NF-κB-p65 expression and activity (by p65 short interfering RNA (siRNA) and pyrrolidine dithiocarbamate, respectively) in chondrocytes reversed the proepithelin-mediated induction of cell proliferation and differentiation and the proepithelin-mediated prevention of cell apoptosis. The inhibition of the phosphatidylinositol 3-kinase and Akt abolished the effects of proepithelin on NF-κB activation. Endogenously produced proepithelin by chondrocytes[so produced by the chondrocytes itself] is important for chondrocyte growth in serum-deprived conditions."

Stimulating proepithelin production by chondrocytes may be a way of increasing height.  Proepithelin may help without active growth plates as it stimulates cellular differentiation as well.

"Proepithelin is highly expressed in growth plate cartilage during embryonic and postnatal development. Its expression in musculoskeletal tissues appears to be restricted to chondrocytes, and it is concentrated in areas where ossification occurs, because it is localized exclusively in the lower proliferative and upper hypertrophic zones of the growth plate chondrocytes and is absent from osteocytes, osteoblasts, periosteum, and perichondrium. In vivo genetic knockdown studies of proepithelin showed a sharp reduction in skeletal length, bone volumes, and cortical bone thickness.  In patients with arthritis, both mRNA and protein levels of proepithelin were up-regulated, indicating that proepithelin may be critical for chondrogenesis"<-But does transgenic expression of proepithelin increase bone length further? As of now there are very few studies related to proepithelin so it is very under-explored in terms of increasing height.

"proepithelin-mediated activation of Akt is IRS-1-independent"

"Proepithelin, also known as granulin epithelin precursor 1, progranulin, PC cell-derived growth factor, or acrogranin, is the only known growth factor able to bypass the insulin-like growth factor receptor."<-IGFR is a possible negative feedback mechanism inhibiting height growth since proepithelin bypasses this negative feedback mechanism proepithelin has the ability to enhance height growth further than compounds like IGF-1 which cannot bypass the IGFR negative feedback mechanisms.

"proepithelin [may activate] AKT through an unidentified pathway"<-this might be how proepithelin exerts it's anabolic effects.

"Proepithelin is biologically active at an optimal effective dose of 240 nM"

"the NF- B subunit p65 facilitates growth plate chondrogenesis via the PI3K/Akt pathway"

"The addition of 10 M wortmannin (a PI3K inhibitor) or 10 M Akti1/2 (an Akt inhibitor) to the culture medium of proepithelin-treated chondrocytes significantly reversed the stimulatory effects of proepithelin on NF- B-p65 DNA-binding activity. In contrast, the addition of U0126 (a MAPK inhibitor), H-89 (a PKA inhibitor), or bisindolylmaleimide I (a PKC inhibitor) did not affect the proepithelin-mediated increase of NF kappaB-p65 activity. In the absence of proepithelin in the culture medium, none of these inhibitors had any effect on NF- B-p65 DNA-binding activity in chondrocytes"<-So proepithelin likely acts through NFkappaB-p65 through the PI3K/Akt pathway.

"cyclin D1 is known as a NF- kappaB induced gene that encodes molecules involved in cell proliferation"<-So cyclin D1 may be a mechanism in which NF-kappaB affects height growth.

"NF-kappa B was detectable in cyclin D1 promoter at 12 and 24 h after proepithelin stimulation."

"Proepithelin increased the height of the epiphyseal, hypertrophic, and proliferative zones of the growth plate

"endogenously produced proepithelin contributes to the ability of chondrocytes to grow in the absence of serum."

"Overexpression of proepithelin stimulates the proliferation of chondrocytes, and cartilage oligomeric matrix protein appears to be required for proepithelin-mediated chondrocyte proliferation in cartilage"<-this finding a way to induce overexpression of proepithelin may be a way to induce height growth.

"proepithelin regulates growth plate chondrogenesis and longitudinal bone growth by inducing the activity of NF-kappa B in growth plate chondrocytes"<-thus other activates of inducing NF-kappaB activity may be longitudinal growth stimulating as well.

"proepithelin may be an attractive medication with little toxicity to normal cells."<-So proepithelin may be a height increasing pill in the future.

So during development proepithelin stimulates longitudinal bone growth. Even afterwards it may help you grow taller by encouraging differentiation into chondrocytes. The scientists seems to believe that proepithelin should be developed into a pill. When this pill is developed, it's consumption may help you grow taller.