user71636274916194
Iron
- Joined
- Mar 27, 2026
- Posts
- 71
- Reputation
- 27
How to optimise the CBP and p300 path way for synergistic effects with any bone compound .
What is CBP and p300 role in bone anabolism ?
CBP and p300 interact with runX2 by preventing its break down from Smurf1 thus allowing it to be kept at high levels in the cell and it also recruits CBP and p300 to up regulate osteocalcin .
CBP and p300 also super critical for b catetin effects on bone formation and anabolism because b catetin once inside the cell it can’t bind to the dna alone it has to bind to TCF/LEF transcription factors what then results in recruiting either CBP or p300 and when for example b catetine binds to CBP it keeps MSC dividing and in like a proliferating state whereas when it binds to p300 it exerts outs anabolic effects by forcing the msc to stop dividing and mature into ostoblast.
Ok so what compounds can we use to up regulate CBP and p300 ?
Rolipram/ abalo :
How does rolipram ( roli ) and abalo up regulate CBP and p300 ? Well roli up regulates it by inhabiting PDE4 enzyme what then prevents the beak down of cAMP thus activating PKA and PKA phosphorylates the transcription factor CREB what then this directly recruits CBP and p300.
Abalo works the exact same way except it triggers a sharp spike in cAMP what then activates and up regulate PKA thus resulting in the phosphorylates of CREB and recruitment or CBP and p300 .
Hif1 effects on CBP and p300 :
Hif1 stabilises BCL9 and BCL9 acts like a messenger/ bridge connecting pygopus to b catetin to then bind to TCF/LEF transcription factors as I said in my above explanation so up regulating BCL9 would make this whore process much more efficient hif1 does this ( via binding to HRE-B and HRE-C ) thus stabilising bcl9 and causing a sharp spike in bcl9 mRNA.
Roxadusant/ DFO or both can be used for hif1 up regulation they do this by roxadustant stripping away the PHD enzyme that lets the vfl protein recognise hif 1/2 and DOF strips away the iron cofactor ( the enzymes needed for vfl to function ) this causes like a massive spike in hif1/2 and mimics a super low oxygen environment . ( Roxadusant can up regulate hif1 )
Eldecalcitol ( ELD ) / Alfacalcidol ( ALF ):
ELD and Alf are both synthetic analogs of vitamin d that trigger up regulation of CBP and p300 via a causing a massive spike in EGR1 . It does this via a non genomic path way that I will try to explain now .
Non genomic path way : ELD and afl bind to either the VDR ( vitamin d receptor) or PDIA3 receptor ( Protein disulfide isomerase family a member 3 ) this then triggers a massive spike of intracelular calcium causing a spike in the enzyme phospholipase c what then hydrolyses membrane phospholipids into DAG and IP3.
The elevated DAG and intracelular calcium directly up regulate the PKC path ways more so specifically the PKCa/b isoforms thus resulting into the recruitment of smallGTP proteins what then recruits the Ras protein.
This ras protein recruitment causes a up regulation and again recruitment lf another protein called Raf-1 into the cell membrane thus phosphorylating it into its active form thus triggering the up regulation of mek1/2 which the phosphorylates erk1/2 on thier threonine and tyrosine residues, and once erk1/2 have been phosphorylated they enter the nucleus and now directly phosphorylates msk1/2 and Elk1 this then results in the production of SRF what then the phosphorylated Elk1 binds to form a Ternary complex what then docks on to specific SREs located in the ERG1 gene what then up regulates CBP and p300 .
Insulin:
Insulin binds to the insulin receptor ( in this case the intracelular a-subunits ) of the insulin receptor ( IR ) what then triggeres the autophosphorylation of the tyrosine located at the intracelular b-subunits this then causes the phosphorylation of the IRS1/2 thus making it able to bind to Grb2-SOS.
This then triggers the up regulations of the ras protein what then again recruits and and activates raf1 thus resulting int the phosphorylation of mek1/2 what then causes the phosphorylation of erk1/2, once inside the nucleus now erk1/2 causes the phosphorylation of Elk1 and then couples with SRF now this protein complex to bind to SRE specifically on the c-foc promoter region causing the massive spike of c-foc mRNA while also the insulin signaling forces up regulation of the c-jun mRNA thus causing erk driven changes in the c-jun and and fra-1 to up regulate ap-1 .
Now the c-jun and fra-1 can bind to ap-1 sites in the dna to exert their transcripts effects on CBP and p300 like fra-1 stabilising and increasing the binding stability or CBP and p300.
And lastly another way we can not necessarily up regulate CBP and p300 but make sure the runX2 and b catetin exert their genomic effects is via ar/er/gr supression as they all compete for CBP and p300 to exert their genomic effects.
This is one way and the most unavailable way why we see ar blinding load in studies is simply that ar activation competes with runX2 abs b catetin for genomic transcripts CBP and p300 henge why we also see that castrated mice end up having more load gains then wt ( wild type ) and other androgen treated groups liken with t or dht.
One simple way we can supress depletion of CBP and p300 from ar and er is via running a 1-2 month cycle of ( ideally 19 nor compounds ) to fully suppress your HPTA . Also I wanted to mention and something that I’ve never seen before talked about the fact that b catetin can bind to the ar itself and essentially be prevented from exerting any of its wnt anabolic pathways this happens because the ar and wnt binding sites overlap i will be linking the study i saw this in in the comments .
ILY for reading and thanks again especially for the 500 followers yaaay mwah . ( TikTok 19nor_abuse )
What is CBP and p300 role in bone anabolism ?
CBP and p300 interact with runX2 by preventing its break down from Smurf1 thus allowing it to be kept at high levels in the cell and it also recruits CBP and p300 to up regulate osteocalcin .
CBP and p300 also super critical for b catetin effects on bone formation and anabolism because b catetin once inside the cell it can’t bind to the dna alone it has to bind to TCF/LEF transcription factors what then results in recruiting either CBP or p300 and when for example b catetine binds to CBP it keeps MSC dividing and in like a proliferating state whereas when it binds to p300 it exerts outs anabolic effects by forcing the msc to stop dividing and mature into ostoblast.
Ok so what compounds can we use to up regulate CBP and p300 ?
Rolipram/ abalo :
How does rolipram ( roli ) and abalo up regulate CBP and p300 ? Well roli up regulates it by inhabiting PDE4 enzyme what then prevents the beak down of cAMP thus activating PKA and PKA phosphorylates the transcription factor CREB what then this directly recruits CBP and p300.
Abalo works the exact same way except it triggers a sharp spike in cAMP what then activates and up regulate PKA thus resulting in the phosphorylates of CREB and recruitment or CBP and p300 .
Hif1 effects on CBP and p300 :
Hif1 stabilises BCL9 and BCL9 acts like a messenger/ bridge connecting pygopus to b catetin to then bind to TCF/LEF transcription factors as I said in my above explanation so up regulating BCL9 would make this whore process much more efficient hif1 does this ( via binding to HRE-B and HRE-C ) thus stabilising bcl9 and causing a sharp spike in bcl9 mRNA.
Roxadusant/ DFO or both can be used for hif1 up regulation they do this by roxadustant stripping away the PHD enzyme that lets the vfl protein recognise hif 1/2 and DOF strips away the iron cofactor ( the enzymes needed for vfl to function ) this causes like a massive spike in hif1/2 and mimics a super low oxygen environment . ( Roxadusant can up regulate hif1 )
Eldecalcitol ( ELD ) / Alfacalcidol ( ALF ):
ELD and Alf are both synthetic analogs of vitamin d that trigger up regulation of CBP and p300 via a causing a massive spike in EGR1 . It does this via a non genomic path way that I will try to explain now .
Non genomic path way : ELD and afl bind to either the VDR ( vitamin d receptor) or PDIA3 receptor ( Protein disulfide isomerase family a member 3 ) this then triggers a massive spike of intracelular calcium causing a spike in the enzyme phospholipase c what then hydrolyses membrane phospholipids into DAG and IP3.
The elevated DAG and intracelular calcium directly up regulate the PKC path ways more so specifically the PKCa/b isoforms thus resulting into the recruitment of smallGTP proteins what then recruits the Ras protein.
This ras protein recruitment causes a up regulation and again recruitment lf another protein called Raf-1 into the cell membrane thus phosphorylating it into its active form thus triggering the up regulation of mek1/2 which the phosphorylates erk1/2 on thier threonine and tyrosine residues, and once erk1/2 have been phosphorylated they enter the nucleus and now directly phosphorylates msk1/2 and Elk1 this then results in the production of SRF what then the phosphorylated Elk1 binds to form a Ternary complex what then docks on to specific SREs located in the ERG1 gene what then up regulates CBP and p300 .
Insulin:
Insulin binds to the insulin receptor ( in this case the intracelular a-subunits ) of the insulin receptor ( IR ) what then triggeres the autophosphorylation of the tyrosine located at the intracelular b-subunits this then causes the phosphorylation of the IRS1/2 thus making it able to bind to Grb2-SOS.
This then triggers the up regulations of the ras protein what then again recruits and and activates raf1 thus resulting int the phosphorylation of mek1/2 what then causes the phosphorylation of erk1/2, once inside the nucleus now erk1/2 causes the phosphorylation of Elk1 and then couples with SRF now this protein complex to bind to SRE specifically on the c-foc promoter region causing the massive spike of c-foc mRNA while also the insulin signaling forces up regulation of the c-jun mRNA thus causing erk driven changes in the c-jun and and fra-1 to up regulate ap-1 .
Now the c-jun and fra-1 can bind to ap-1 sites in the dna to exert their transcripts effects on CBP and p300 like fra-1 stabilising and increasing the binding stability or CBP and p300.
And lastly another way we can not necessarily up regulate CBP and p300 but make sure the runX2 and b catetin exert their genomic effects is via ar/er/gr supression as they all compete for CBP and p300 to exert their genomic effects.
This is one way and the most unavailable way why we see ar blinding load in studies is simply that ar activation competes with runX2 abs b catetin for genomic transcripts CBP and p300 henge why we also see that castrated mice end up having more load gains then wt ( wild type ) and other androgen treated groups liken with t or dht.
One simple way we can supress depletion of CBP and p300 from ar and er is via running a 1-2 month cycle of ( ideally 19 nor compounds ) to fully suppress your HPTA . Also I wanted to mention and something that I’ve never seen before talked about the fact that b catetin can bind to the ar itself and essentially be prevented from exerting any of its wnt anabolic pathways this happens because the ar and wnt binding sites overlap i will be linking the study i saw this in in the comments .
ILY for reading and thanks again especially for the 500 followers yaaay mwah . ( TikTok 19nor_abuse )
