Tesarossa
Htn | 6’1 | 22.5” Bidelt | Fuoty 3026 ⚝
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Table Of Content
Summary
Story
In Depth Guide
How to inhibit the indian Hedgehog
Thread Song
Story| Indian Hedgehog The Knight
Summary
Story
In Depth Guide
How to inhibit the indian Hedgehog
Thread Song
Story| Indian Hedgehog The Knight
In the deep halls of the growing skeleton there rode a knight named Indian Hedgehog. Born among the pre hypertrophic chondrocytes, he carried a precise and powerful signal that ruled the growth plate. Through his alliance with PTHrP he held chondrocytes in the proliferative ranks, delaying their final maturation so the columns stayed ordered and the bone could lengthen at the proper pace. At the same time he turned to the perichondrium, summoning osteoblast progenitors to form the bone collar and begin the laying down of true bone.
His watch did not end at birth. Postnatally he continued to guard the growth plate from premature collapse and helped sustain the trabecular bone beneath. In the fetal limbs his influence reached the developing muscle as well, shielding myoblasts so secondary fibers could form in strength and number. When the knight’s signal failed, the bones shortened, the growth plates fell into disorder, ossification faltered, and the limb muscles weakened proving that Indian Hedgehog was one of the quiet sovereigns who shaped both the length of the skeleton and the muscle that grew beside it.
His watch did not end at birth. Postnatally he continued to guard the growth plate from premature collapse and helped sustain the trabecular bone beneath. In the fetal limbs his influence reached the developing muscle as well, shielding myoblasts so secondary fibers could form in strength and number. When the knight’s signal failed, the bones shortened, the growth plates fell into disorder, ossification faltered, and the limb muscles weakened proving that Indian Hedgehog was one of the quiet sovereigns who shaped both the length of the skeleton and the muscle that grew beside it.
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Summary
Indian Hedgehog is a secreted signaling protein and one of the three mammalian Hedgehog ligands.
It is produced mainly by pre hypertrophic and hypertrophic chondrocytes in the growth plate.
Its primary role is regulating endochondral bone growth.
IHH forms a negative feedback loop with PTHrP that controls chondrocyte proliferation versus hypertrophy,
thereby maintaining growth plate length and organization.
It also directly promotes chondrocyte proliferation, drives osteoblast specification and bone collar formation,
and helps maintain the growth plate and trabecular bone after birth.
It is produced mainly by pre hypertrophic and hypertrophic chondrocytes in the growth plate.
Its primary role is regulating endochondral bone growth.
IHH forms a negative feedback loop with PTHrP that controls chondrocyte proliferation versus hypertrophy,
thereby maintaining growth plate length and organization.
It also directly promotes chondrocyte proliferation, drives osteoblast specification and bone collar formation,
and helps maintain the growth plate and trabecular bone after birth.
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In Depth
Molecular identity
Indian Hedgehog is a secreted morphogen belonging to the Hedgehog family.
In mammals it is one of three ligands (with Sonic and Desert Hedgehog).
During endochondral ossification it is produced mainly by pre hypertrophic and early hypertrophic chondrocytes in the growth plate.
The active N terminal signaling fragment is generated by autoproteolytic cleavage and lipid modification
(cholesterol and palmitoylation), which are required for proper secretion and long range signaling.
Signaling
IHH binds Patched (PTCH1). This relieves PTCH mediated repression of Smoothened (SMO).
Activated SMO initiates intracellular signaling that culminates in the Gli transcription factors.
In the growth plate, Gli3 functions predominantly as a repressor, while Gli1, Gli2 and Gli3 together mediate osteoblast related responses.
The pathway can act both locally and as a concentration dependent morphogen.
The negative feedback loop (central mechanism)
IHH secreted by pre hypertrophic chondrocytes induces PTHrP expression in periarticular chondrocytes and perichondrial cells.
PTHrP then acts on its receptor (PTH1R) on proliferating chondrocytes to keep them in the proliferative pool and delay their entry into hypertrophy.
As the growth plate elongates, the distance between the IHH source and the PTHrP producing cells increases, lowering the local IHH signal and allowing controlled progression to hypertrophy.
This loop is the main mechanism that maintains growth plate length and organization both embryonically and postnatally.
Effects on muscle
During fetal secondary myogenesis, bone derived IHH supports myoblast survival.
Ihh null embryos show markedly increased myoblast apoptosis (linked to loss of p21) and substantial reduction in limb muscle mass.
These muscle defects occur even when bone length changes are accounted for, indicating a relatively direct contribution of IHH to fetal muscle growth.
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How To Inhibit Said Pathway
Smoothened (SMO) inhibitors
Cyclopamine | Natural steroidal alkaloid (from Veratrum plants); the original tool compound that blocks SMO.
Vismodegib (GDC-0449, Erivedge) Oral SMO inhibitor approved for basal cell carcinoma.
Sonidegib (LDE-225, Odomzo) Another oral SMO inhibitor approved for basal cell carcinoma.
Glasdegib (PF-04449913, Daurismo) SMO inhibitor approved in combination regimens for certain leukemias.
Additional clinical or investigational SMO inhibitors include saridegib, taladegib, and others in earlier development.
Downstream Gli inhibitors
GANT61 and GANT58 Experimental small molecules that inhibit Gli mediated transcription.
Other experimental Gli antagonists (natural product derived or synthetic) have been described in research settings.
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This pathway name is funny as shit
I had it in a doc for like a week
@fallen442 @-joe @stalk @Jordan Barrett @Organ
@stalk thanks for some of the india pics
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This pathway name is funny as shit
