Aug 2, 1996

Regulation of rate of cartilage differentiation by Indian hedgehog and PTH-related protein

Science
Andrea VortkampC J Tabin

Abstract

Proper regulation of chondrocyte differentiation is necessary for the morphogenesis of skeletal elements, yet little is known about the molecular regulation of this process. A chicken homolog of Indian hedgehog (Ihh), a member of the conserved Hedgehog family of secreted proteins that is expressed during bone formation, has now been isolated. Ihh has biological properties similar to those of Sonic hedgehog (Shh), including the ability to regulate the conserved targets Patched (Ptc) and Gli. Ihh is expressed in the prehypertrophic chondrocytes of cartilage elements, where it regulates the rate of hypertrophic differentiation. Misexpression of Ihh prevents proliferating chondrocytes from initiating the hypertrophic differentiation process. The direct target of Ihh signaling is the perichondrium, where Gli and Ptc flank the expression domain of Ihh. Ihh induces the expression of a second signal, parathyroid hormone-related protein (PTHrP), in the periarticular perichondrium. Analysis of PTHrP (-/-) mutant mice indicated that the PTHrP protein signals to its receptor in the prehypertrophic chondrocytes, thereby blocking hypertrophic differentiation. In vitro application of Hedgehog or PTHrP protein to normal or PTHrP (-/-) limb exp...Continue Reading

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Mentioned in this Paper

Parathyroid Hormone Peptide (1-34)
Hedgehog Proteins
Periarticular Route of Administration
Chondrocyte Differentiation
Hypertrophic Cardiomyopathy
Parathyroid hormone-related protein
Receptors, Parathyroid Hormone
Perichondrium
Gene Products, Protein
Hypertrophy

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