“the expression of 688 genes (ANOVA false discovery rate modified p-value, q < 0.1) was associated with age, and subsets of these genes formed clusters that correlated with the phases of growth — infancy, childhood, puberty and [adult] height.”<-It seems that the genes are correlated with stage of development and not directly associated with differences in height.
“Network analysis on these clusters identified evolutionarily conserved growth pathways (NOTCH, VEGF, TGFB, WNT and glucocorticoid receptor)”
“Similar biological pathways were observed to be associated with development-related gene expression in other tissues (conjunctival epithelia, temporal lobe brain tissue and bone marrow) suggesting the existence of a tissue-independent genetic program for human growth and maturation.”
Gene expression from peripheral blood mononuclear cells were obtained.
Pathways associated with Adult Stage of Growth:
Ephrin Receptor Signaling:
Related genes upregulated by LSJL:
Epha5, Epha3
Downregulated:
Efnb3
Erythropoietin Signaling(associated with red blood cell production which means that bone marrow could be linked to height)
Related genes downregulated by LSJL:
Zc3h15
Wnt-Beta-Catening Signaling
Related Genes Upregulated by LSJL:
Fzd3, Fzd2, Dkk3,
Downregulated:
Fbxw2, Dvl1, Csnk1e, Hbp1, Tcf7, Csnk1d, Tle2, Senp2
Chemokine Signaling(Chemokines are related to inflammatory and leukocyte signaling)
LSJL Upregulated:
Ccr1, Cxcr7
Downregulated:
Ccrl2, Ccr9
Reelin Signaling Neurons(mostly associated with the brain which is why it’s not detected in LSJL.
Pathways Correlated with height in infancy and puberty are more traditional like BMP, GH, and TGF-Beta.
Pathways associated with Development in Infancy:
PDGF Signaling
VEGF Family Lig and-Receptor Interactions
VEGF Signaling
Angiopoietin Signaling
NGF Signaling
Melanocyte Development and Pigmentation Signaling
Renin-Angiotensin Signaling
NF-B Signaling
Notch Signaling
IGF-1 Signaling
Erythropoietin Signaling
Chemokine Signaling
Wnt/Beta-catenin Signaling
TGF-Beta Signaling
BMP signaling pathway
Neurotrophin/TRK Signaling
Ephrin Receptor Signaling
Growth Hormone Signaling
Axonal Guidance Signaling
Pathways Associated with Development in Puberty:
IGF-1 Signaling
Chemokine Signaling
Actin Cytoskeleton Signaling
Axonal Guidance Signaling
Wnt/B-catenin Signaling
TGFB- Signaling
Ephrin Receptor Signaling
VEGF Signaling
VEGF Family Lig and-Receptor Interactions
Renin-Angiotensin Signaling
NF-B Signaling
Notch Signaling
Regarding Reelin Signaling Neurons and Bone:
“Limb bones contain greater amounts of polysulphated glycosaminoglycan stained with Alcian Blue and have significantly higher osteocyte densities than skull bone. Site-specific patterns persist in cultured adult bone-derived cells both phenotypically (proliferation rate, response to estrogen and cell volumes), and at the level of specific gene expression (collagen triple helix repeat containing 1, reelin and ras-like and estrogen-regulated growth inhibitor). Based on genome-wide mRNA expression and cluster analysis, we demonstrate that bones and cultured adult bone-derived cells segregate according to site of derivation. We also find the differential expression of genes associated with embryological development (Skull: Zic, Dlx, Irx, Twist1 and Cart1; Limb: Hox, Shox2, and Tbx genes) in both adult bones and isolated adult bone-derived cells.”
Reeln expression is elevated in limb versus skull bones. Reeln is speculated to be involved in the osteocytic mechanical response of long bones.
Both Reeln and Cthrc1 are mentioned as therapeutic targets albeit for bone mass and not height growth.
