user71636274916194
Iron
- Joined
- Mar 27, 2026
- Posts
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How we can mimic a vfl ko environment for appositional growth :
What effects does inhibiting vfl does to bones and what is vfl :
Vfl is a protein that actively targets hif1/2 and when it attaches to it it attaches a chain of of small proteins called uniquitin on to it this like marks it to be dragged to the proteasome to be actively disposed of .
Also I forgot to mention when ur cells sense they have enough oxygen they make PDHs what then attaches a chemical tag directly on the hif. This then allows for the vfl to target the tagged hif by the PDHs.
Why do we want to supress PDHs/ vfl ?
The main reason why we want to supresses them is due to the fact that I’ll allow for both hif1/2 to continuously build up in the bone tissues mimicking a low oxygen environment and as seen in vfl ko mice this results in noticeably wider and robust bones:
What drugs could we use to mimic this scenario ?
Roxadusant:
Roxadustant works by stripping away the PDH enzyme what lets the vfl protein recognise hif1/2 thus allowing the constant accumulation of hif .
In vivo roxadustant has seen to up regulate wnt runx2 and b-catetin and Inhbit ostoclasts via RANKL induced osteoclast differentiation.
DOF:
DOF works via stripping away the iron cofactor thus inhibiting vfl from property functioning. Low dose DOF has been seen to promote vegf stabilise hif1/2 and promote angiogenesis and the proliferation of ostoblast.
Proteasome inhibition:
Drugs like carfilzomib or bortezombin Inhbit the proteasome from degrading hif1/2 actively letting it acumulate thus keeping that “ low oxygen environment “ also they prevent the break down of runx2 and b b-catenin and also Inhbit the NF-kB resulting in down regulation of RANKL.
Hadjod:
Hadjod is a plant known to help with fracture healing and preventing bone loss from osteoporosis hadjod has been observed to stabilise hif1 via up regulating SIRT1 what then physically removes the acetyl groups from hif-1a.
Viagra:
Viagra works via also via mimicking the effects of hif1. It does this via preventing the the break down of cGMP what then triggers pro angiogenic singles that hif1 would normally turn on thus up regulating vegf.
Dosing:
Roxadustant 1.5-2mg per kg everyday
DOF 7-9mg per kg everyday
Hadjod 1.2-2g 3x a day
Bortezombin ( needs to be cycled )
Days 1-4-8-11 then a 10 day break and repeat on the days u need to take it 2-2.5mg subq
Viagra 0.8mg per kg
What effects does inhibiting vfl does to bones and what is vfl :
Vfl is a protein that actively targets hif1/2 and when it attaches to it it attaches a chain of of small proteins called uniquitin on to it this like marks it to be dragged to the proteasome to be actively disposed of .
Also I forgot to mention when ur cells sense they have enough oxygen they make PDHs what then attaches a chemical tag directly on the hif. This then allows for the vfl to target the tagged hif by the PDHs.
Why do we want to supress PDHs/ vfl ?
The main reason why we want to supresses them is due to the fact that I’ll allow for both hif1/2 to continuously build up in the bone tissues mimicking a low oxygen environment and as seen in vfl ko mice this results in noticeably wider and robust bones:
What drugs could we use to mimic this scenario ?
Roxadusant:
Roxadustant works by stripping away the PDH enzyme what lets the vfl protein recognise hif1/2 thus allowing the constant accumulation of hif .
In vivo roxadustant has seen to up regulate wnt runx2 and b-catetin and Inhbit ostoclasts via RANKL induced osteoclast differentiation.
DOF:
DOF works via stripping away the iron cofactor thus inhibiting vfl from property functioning. Low dose DOF has been seen to promote vegf stabilise hif1/2 and promote angiogenesis and the proliferation of ostoblast.
Proteasome inhibition:
Drugs like carfilzomib or bortezombin Inhbit the proteasome from degrading hif1/2 actively letting it acumulate thus keeping that “ low oxygen environment “ also they prevent the break down of runx2 and b b-catenin and also Inhbit the NF-kB resulting in down regulation of RANKL.
Hadjod:
Hadjod is a plant known to help with fracture healing and preventing bone loss from osteoporosis hadjod has been observed to stabilise hif1 via up regulating SIRT1 what then physically removes the acetyl groups from hif-1a.
Viagra:
Viagra works via also via mimicking the effects of hif1. It does this via preventing the the break down of cGMP what then triggers pro angiogenic singles that hif1 would normally turn on thus up regulating vegf.
Dosing:
Roxadustant 1.5-2mg per kg everyday
DOF 7-9mg per kg everyday
Hadjod 1.2-2g 3x a day
Bortezombin ( needs to be cycled )
Days 1-4-8-11 then a 10 day break and repeat on the days u need to take it 2-2.5mg subq
Viagra 0.8mg per kg
