Indian hedgehog couples chondrogenesis to osteogenesis in endochondral bone development
Ung-il Chung, … , Andrew P. McMahon, Henry M. Kronenberg
Ung-il Chung, … , Andrew P. McMahon, Henry M. Kronenberg
Published February 1, 2001
Citation Information: J Clin Invest. 2001;107(3):295-304. https://doi.org/10.1172/JCI11706.
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Article

Indian hedgehog couples chondrogenesis to osteogenesis in endochondral bone development

Abstract

Vertebrate skeletogenesis requires a well-coordinated transition from chondrogenesis to osteogenesis. Hypertrophic chondrocytes in the growth plate play a pivotal role in this transition. Parathyroid hormone–related peptide (PTHrP), synthesized in the periarticular growth plate, regulates the site at which hypertrophy occurs. By comparing PTH/PTHrP receptor–/–/wild-type (PPR–/–/wild-type) chimeric mice with Ihh–/–;PPR–/–/wild-type chimeric and Ihh–/–/wild-type chimeric mice, we provide in vivo evidence that Indian hedgehog (Ihh), synthesized by prehypertrophic and hypertrophic chondrocytes, regulates the site of hypertrophic differentiation by signaling to the periarticular growth plate and also determines the site of bone collar formation in the adjacent perichondrium. By providing crucial local signals from prehypertrophic and hypertrophic chondrocytes to both chondrocytes and preosteoblasts, Ihh couples chondrogenesis to osteogenesis in endochondral bone development.

Authors

Ung-il Chung, Ernestina Schipani, Andrew P. McMahon, Henry M. Kronenberg

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Figure 1

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Ectopic differentiation of growth plate chondrocytes deficient in PTHrP ...
Ectopic differentiation of growth plate chondrocytes deficient in PTHrP signaling. (a–c) Sections of the tibiae from d17.5 wild-type (a), PTHrP–/– (b), and PPR–/– (c) embryos were stained with H&E. The growth plates of PTHrP–/– mice and PPR–/– mice have a shorter layer of columnar proliferating chondrocytes. In PTHrP–/– mice, they represent less than 30% of wild-type (b, bracket), and in PPR–/– mice, they are almost completely absent (c, arrowhead). (d–g) H&E staining and in situ hybridization with a mouse type X collagen antisense probe of the sections of the tibiae from d17.5 PPR–/–/wild-type chimera (d and e, respectively) and Ihh–/–;PPR–/–/wild-type chimera (f and g, respectively) embryos. In the absence of PTHrP signaling, mutant cells ectopically hypertrophy when they move from the layer of periarticular proliferating chondrocytes into the layer of columnar proliferating chondrocytes (arrowheads). Staining for β-galactosidase activity of both chimeric growth plates shows that all the mutant chondrocytes undergo ectopic hypertrophy, whereas wild-type cells do not (data not shown). Horizontal bar = 100 μm.