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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

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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 5

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Expression of osteoblastic markers in the chimeric growth plates. (a–c) ...
Expression of osteoblastic markers in the chimeric growth plates. (a–c) In situ hybridization of sections of the tibiae from d17.5 embryos with a mouse osteopontin antisense probe. In the wild-type growth plate (a), osteopontin mRNA is expressed in osteoblasts as well as in mature chondrocytes, and its expression pattern overlaps the locations of bone collars and cartilaginous mineralization. In the PPR–/–/wild-type chimera growth plate (b), there is ectopic expression of osteopontin mRNA in ectopic bone collars (bracket). Ectopic hypertrophic chondrocytes also express osteopontin mRNA (asterisk). In contrast, in the Ihh–/–;PTH/PPR–/–/wild-type chimera (c), there is no ectopic expression of osteopontin mRNA in the perichondrium, whereas ectopic hypertrophic chondrocytes still express osteopontin mRNA (asterisk). Arrowheads denote where the eutopic prehypertrophic layer starts. (d–f) In situ hybridization of sections of the tibiae from d17.5 embryos with a mouse osteocalcin antisense probe. In the wild-type growth plate (d), osteocalcin mRNA is expressed in mature osteoblasts. In the PPR–/–/wild-type chimera (e), there is ectopic expression of osteocalcin mRNA in ectopic bone collars (bracket), whereas in the Ihh–/–;PPR–/–/wild-type chimera (f), there is no ectopic expression of osteocalcin mRNA in the perichondrium. Arrowheads denote where the eutopic prehypertrophic layer starts. Horizontal bar = 100 μm.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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