Height Growth Protein Map

 Key: 
- downregulate
+ upregulate
-> transcription regulation
+/- means the result is dose or experiment dependent


Okay here's a draft of the genetic regulation involved height growth.  We want to focus mainly on the genes that promote chondrogenesis although eventually we'll go through genes that maximize height.  These up- and down- regulations may not happen all the time but showed up in at least one study and may be dose and/or environment dependent.


Key factors in initiating height growth seem to be inhibiting the NFKappaB pathway and Runx2.   Although this study here shows no effect of Runx2 on bone length. Sox9 and the interplay between TGFBeta1 and BMP2 seem key to initiating a new growth plate.  Finding the TGF and BMP Smad interplay will be key in developing therapies to grow taller as will PTH/IHH interplay.


Posting this now to get feedback on genes/interactions I'm missing.  Eventually I'll draw a graphic representing the interaction.  Also, take note of Harpogoside and Acteoside which inhibit NFKappaB activity.  Two supplements that I looked at earlier that take on additional relevance now due to the importance of NFKappaB on height growth.


Also, tomorrow I'll be posting an LSJL finger update.




Sox9 -> Col2a1(intron 1, intron 6)


IL1:
- Sox9
- chondrocyte proliferation
+MMPs


TNFalpha:
-Sox9


FGFs:
+Sox9
-Ihh


PKA+Sox9
S181+Sox9


TGFBeta:
+Sox9
+Aggrecan
+Col2A1
+BMP2
+Smad2/3P
+F-spondin
-cartilage tissue growth(encourages homeostasis)
+Fibronectin


BMPs:
+Ihh
-PTHrP


BMP2:
+Sox9
+Aggrecan
+Col2A1
+Smad1/5/8P
+Beta-Catenin
-TGFBeta1


BMP7:
+cartilage tissue growth
+GAGs


LIPUS:
+BMP2
+FGF7
+TGFBetaR1
+EGFR1
+VEGF
+PI3K
-GSK3Beta


IGF-1:
-RhoA
+cartilage tissue growth
+GAGs
+Twist1


Noggin:
-BMP
-Height


Gremlin:
-BMP


Chordin:
-BMP


Bezafibrate:
+BMP2
+RUNX2


RhoA:
-chondrogenesis
-chondrocyte maturation
+PI3K


Rac1:
-chondrogenesis
+chondrocyte maturation
+alkaline phosphatase
+adhesion
+Col2A1
+Aggrecan
-GAGs
+Sox9


Mechanical Loading:
+TGFBeta1
+IGF-1


LSJL:
+/-MMP3(depends on load)
-MMP1
-MMP8
-MMP13
+hyaluranon synthase 1
+TIMP1
+GAGs
+Interleukin 1 receptor-like 1
-TNF
+TGF-Beta1
+TGF-BetaR1
+Follistatin
+ActivinR1
-EIF2alpha phosphorylation
+CITED2
+Actin filament remodeling


Icariin:
+BMP2
+BMP4
+Cpfalpha1
-COX2
-PGE


PEMF:
+proteoglycans
+ECM
+Col2A1
+/-ALP
+MMP2
+Sox9
+MT1-MMP
+proteoglycan sulfation
-Collagen Type X


FGF:
-Ihh


FGF2:
-cellular senescence


FGFR3:
-height


SUMF1:
+Activate sulfates that catalyze desulfation of the GAGs moiety of proteoglycans in the intracellular and extracellular space. 
+ECM
+height
-FGF


CHOP:
+apoptosis
+IL1
+IL6


AKT1:
-caspase3
+BclXL
+chondrocyte survival


Salubrinal:
+EIF2alpha phosphorylation
+ATF3
+ATF4
+Chop
-Cell death


Mechanical Loading:
Alteration in cortical actin dynamics resulting in adaptation to load.


MT1-MMP:
+cartilage canals


Endoglin:
+Smad 1/5P
-Smad 2P


Smad2/3P(ALK5):
+Type II Collagen


Smad 1/5/8P(ALK1):
+Type X Collagen
+MMP13
-Height


ESL1:
+Height
-TGFBeta1


Cnidium:
+bFGF
+BMP-2
+IGF-1


RA:
+F-Spondin


Beta-Catenin:
-Chondrogenesis
-Sox9


F-Spondin:
-Height
+MMP-13
+ALP


Extracellular P(i):
+ALP
+RUNX2
+MMP-13


Smurf1:
-BMPs
-Height


Smad6:
-Height
-Smad1/5/8P
-BMPs


Smad7:
-TGF-Beta1
-BMP2


PTHrP:
+Sox9
+chondrocyte hypertrophy


IHH:
+chondrocyte proliferation
-Nkx3.2


FGFR1:
-Chondrogenesis


FGFR3:
+STAT1
-Height
-Ihh


STAT1:
-CCND1


CCND1:
-Runx2


FGF18:
-chondrocyte proliferation


Dynamic Compression(60min):
+COL2A1


MAPK(in chondrocytes):
+accelerates endochondral ossification


Microgravity:
+Sox9
+Aggrecan
+Type II Collagen


Ecdysterone:
+chondrogenesis


Twist1:
-Sox9


NfKappaB:
-Sox9


Runx2:
-Sox9


PTHrP:
+NLK3.2


Nkx3.2:
+Sox9
+Col2A1


Silicon:
+ALP
-Height


TSP3:
+Height


TSP5:
+Height


Col9:
+Height


Insulin:
-IGF1R
-IR


PGE2:
+IL6
+Type II Collagen
+MMP13
-Type X Collagen
-BMPs


Ascorbic Acid:
+ERK
+helps synthesize collagen matrix


Hydrostatic Pressure:
+Mitotic cell rounding into chondrogenesis


CNP:
+Height
+cGMP


CCN2:
+/- Height


Estrogen:
+/- Height


Proepithelin:
-NFKappaB
+Height


Harpogoside:
-MMP1
-MMP3
-MMP13
-NFKappaB


Acteoside:
-NFKappaB