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Discovery of Sonic hedgehog expression in postnatal growth plate chondrocytes: Differential regulation of Sonic and Indian hedgehog by retinoic acid
Author(s) -
Wu Licia N.Y.,
Lu Min,
Genge Brian R.,
Guo George Y.,
Nie Daotai,
Wuthier Roy E.
Publication year - 2002
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.10285
Subject(s) - sonic hedgehog , indian hedgehog , retinoic acid , hedgehog signaling pathway , endocrinology , biology , medicine , microbiology and biotechnology , chondrocyte , in situ hybridization , hedgehog , cartilage , cellular differentiation , gene expression , signal transduction , anatomy , cell culture , gene , genetics
Sonic hedgehog (Shh) is a key signal protein in early embryological patterning of limb bud development. Its analog, Indian hedgehog (Ihh), primarily expressed during early cartilage development in prehypertrophic chondrocytes, regulates proliferation and suppresses terminal differentiation of postnatal growth plate (GP) chondrocytes. We report here for the first time that both Shh and Ihh mRNA are expressed in the GP of rapidly growing 6‐week‐old broiler‐strain chickens. They are also expressed in other tissues such as articular chondrocytes, kidney, and bone. In situ hybridization and RT‐PCR analyses reveal Shh in all zones of the GP, with peak expression in late hypertrophy. Using primary cultures of GP chondrocytes in serum‐containing medium, we followed the patterns of Shh and Ihh mRNA expression as the cultures matured and mineralized. We find a cyclical expression of both hedgehog genes during the early period of culture development between day 10 and 14; when one is elevated, the other tended to be suppressed, suggesting that the two hedgehogs may play complementary roles during GP development. Retinoic acid (RA), a powerful modulator of gene expression in cell differentiation, stimulates GP chondrocytes toward terminal differentiation, enhancing mineral formation. We find that RA strongly suppresses Ihh , but enhances expression of Shh in this system. While Ihh suppresses maturation of GP chondrocytes to hypertrophy, we hypothesize that Shh acts to push these cells toward hypertrophy. J. Cell. Biochem. 87: 173–187, 2002. © 2002 Wiley‐Liss, Inc.