Abstract
Hedgehog (Hh) signaling plays crucial roles in the patterning and morphogenesis of various organs within the bodies of vertebrates and insects. Endochondral ossification is one of the notable developmental events in which Hh signaling acts as a master regulator. Among three Hh proteins in mammals, Indian hedgehog (Ihh) is known to work as a major Hh input that induces biological impact of Hh signaling on the endochondral ossification. Ihh is expressed in prehypertrophic and hypertrophic chondrocytes of developing endochondral bones. Genetic studies so far have demonstrated that the Ihh-mediated activation of Hh signaling synchronizes chondrogenesis and osteogenesis during endochondral ossification by regulating the following processes: (1) chondrocyte differentiation; (2) chondrocyte proliferation; and (3) specification of bone-forming osteoblasts. Ihh not only forms a negative feedback loop with parathyroid hormone-related protein (PTHrP) to maintain the growth plate length, but also directly promotes chondrocyte propagation. Ihh input is required for the specification of progenitors into osteoblast precursors. The combinatorial approaches of genome-wide analyses and mouse genetics will facilitate understanding of the regulatory mechanisms underlying the roles of Hh signaling in endochondral ossification, providing genome-level evidence of the potential of Hh signaling for the treatment of skeletal disorders.
Highlights
Hedgehog (Hh) signaling plays crucial roles in the patterning and morphogenesis of various organs within the bodies of vertebrates and insects [1]
The compound mutants inhibited premature chondrocyte hypertrophy, but did not increase the number of mitotically active chondrocytes compared to Indian hedgehog (Ihh)/ ́ mutants. These results suggest that: (1) Ihh is required for both the differentiation and the proliferation of growth plate chondrocytes; (2) parathyroid hormone-related protein (PTHrP)
These data suggest that: (1) Ihh has positive effects on chondrocyte proliferation at the postnatal stage, but the effects are unlikely mediated by PPR; and (2) Ihh and PTHrP may functionally interact at postnatal stages, as they do at embryonic stages
Summary
Hedgehog (Hh) signaling plays crucial roles in the patterning and morphogenesis of various organs within the bodies of vertebrates and insects [1]. Gli and Gli are processed into transcriptional repressor forms upon Hh input. Mammalian skeletons are formed by two distinct processes: intramembranous ossification and endochondral ossification. 2016, 4, 20 skeletons are formed by two distinct processes: intramembranous ossification of and endochondral ossification. Mesenchymal cells directly differentiate into the bone-forming cells called osteoblasts. This process forms the frontal bone, into the bone, bone-forming called osteoblasts. During the endochondral ossification are initially formed and replaced by bones. Starts with the condensation of immature mesenchymal cells at a Endochondral ossification. Endochondral ossification starts with condensation of immature mesenchymal cells at a region region where future bone develops. Mature osteoblasts contribute to bone formation by matrixes.
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