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
AWESOME!
ReplyDeleteMissing "hormones":
ER alpha
+ Chondrocyte proliferation
ER beta
- Chondrogenesis
+ Chondrocyte differentiation
- Chondrocyte proliferation
GPR-30
- Chondrogenesis
AR
+ IGF-1
+ IGF-1R
HA
+ CDC42
cGMP
- cAMP
+ PKGII
- SOX9
CNP
+ GAG synthesis
+ Chondrocyte proliferation
WNTs
ReplyDelete+ TWIST1
Calcitonin
ReplyDeletemissed crucial hormones testostorone and growth hormone and whats all this about estrogen have you seen how small and skinny the average girl is compared to a male the less of that girly hormone floating around my system the better.
ReplyDeletehey Tyler
ReplyDeletecan you look up on the term :
"Pseudo-reactivation of growth plate"
"hey Tyler
ReplyDeletecan you look up on the term :
"Pseudo-reactivation of growth plate""
I just searched some. It's patients with TIO that get that? which is because of elevated FGF23?
And Calcium defiency reduces FGF23 levels, (just google)
So Calcium defiency lead to faster growth plate closure?
or maybe adequate levels of Calcium lead to a longer opened growthplate, because FGF23 levels are still high, thus "reactivating/not closing" the plate?