Prx1 seems to be a very promising target for height increase as it seems to have targets early in development. Unfortunately, I couldn’t find any Prx1 stimulating substances but hopefully you can? Srx1 is involved in the repair of Prx1 so that could be another target as well.
Regulatory divergence modifies limb length between mammals
“Natural selection acts on variation within populations, resulting in modified organ morphology, physiology, and ultimately the formation of new species. Although variation in orthologous proteins can contribute to these modifications, differences in DNA sequences regulating gene expression may be a primary source of variation. We replaced a limb-specific transcriptional enhancer of the mouse Prx1 locus with the orthologous sequence from a bat. Prx1 expression directed by the bat enhancer results in elevated transcript levels in developing forelimb bones and forelimbs that are significantly longer than controls because of endochondral bone formation alterations. Surprisingly, deletion of the mouse Prx1 limb enhancer results in normal forelimb length and Prx1 expression, revealing regulatory redundancy. These findings suggest that mutations accumulating in pre-existing noncoding regulatory sequences within a population are a source of variation for the evolution of morphological differences between species and that cis-regulatory redundancy may facilitate accumulation of such mutations.”
“One developmental control gene known to promote limb skeletal elongation is Prx1, also called MHox or Prrx1. Prx1 is a paired-related homeobox gene expressed in somites, craniofacial mesenchyme, and limb mesoderm during mouse development”
“the forelimbs of Prx1BatE/BatE mutants are on average ∼6% longer than their wild-type littermates at E18.5 ”
“The forelimbs of Prx1-null homozygotes are ∼12.5% shorter than controls at E18.5”
“average mutant long bones express ∼70% more Prx1 than wild-type siblings”
“Long bone chondrocyte proliferation is elevated by ∼6% at E15.5 in Prx1BatE/BatE mutants.”
“[The Prx1 induced] limb elongation arises at stages of mouse gestation when Prx1 expression is limited to the perichondrium of the developing limb skeletal elements. It is known that the perichondrium is an important regulator of endochondrial bone growth”<-Could this be related to the zone of Ranvier which should be connected to the perichondrium? Since the zone of Ranvier is linked to an earlier developmental state of the growth plate it could mean that Prx1 could be helpful in inducing neo growth plates.
According to this grant, Prx1 inhibits bone formation so it favors an earlier developmental state overall.
“Increases in mechanical loading can enhance the addition of new bone, altering geometry and density such that bones better withstand higher forces. Bone-forming osteoblasts have long been thought to originate from progenitors, but the exact source is yet to be identified. Previous studies indicate osteogenic precursors arise from Prx1-expressing progenitors during embryonic development and adult fracture repair. However, it is unknown whether this cell population is also a source for mechanically induced active osteoblasts. We first identified that Prx1 is expressed in skeletally mature mouse periosteum, a thin tissue covering the surface of the bone that is rich in osteoprogenitors. We then traced Prx1 progenitor lineage using a transgenic mouse model carrying both a Prx1-driven tamoxifen-inducible Cre and a ROSA-driven lacZ reporter gene. Cells that expressed Prx1 when compressive axial loading was applied were detected within the cortical bone days after stimulation, indicating osteocytes are of Prx1-expressing cell origin. In addition, we evaluated how these cells sense and respond to physical stimulation in vivo by disrupting their primary cilia, which are antenna-like sensory organelles known to enhance mechanical and chemical signaling kinetics. Although Prx1-driven primary cilium disruption did not affect osteoblast recruitment to the bone surface, the relative mineral apposition and bone formation rates were decreased by 53% and 34%, respectively. Thus, this cell population contributes to load-induced bone formation, and primary cilia are needed for a complete response. Interestingly, Prx1-expressing progenitors are easily extracted from periosteum and are perhaps an attractive alternative to marrow stem cells for bone tissue regeneration strategies.”
“periosteum, which surrounds bones and is rich in progenitor cells known to preferentially differentiate towards the osteogenic lineage”
“physical stimulation activates and encourages osteogenic differentiation of progenitors within the periosteum.”
“One potential mechanism by which progenitor cells may become mechanically activated is through the primary cilium. Primary cilia are antenna-like organelles that extend from the cell surface and serve as signaling microdomains.”
“osteogenic response to fluid shear is lost when periosteal progenitor primary cilia are disrupted in vitro”
“Prx1-expressing cells become embedded osteocytes in response to physical loading and this mechanism requires the primary cilium.”<-if Prx1 enhances longitudinal bone growth and Prx1 mainly effects on chondrogenic cells maybe there are non chondrogenic ways to enhance longitudinal bone growth.