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Developmental patterning in chondrocytic cultures by morphogenic gradients: BMP induces expression of Indian hedgehog and Noggin
Author(s) -
Kameda Takashi,
Koike Chika,
Saitoh Kanako,
Kuroiwa Atsushi,
Iba Hideo
Publication year - 1999
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1046/j.1365-2443.1999.00250.x
Subject(s) - noggin , indian hedgehog , hedgehog , microbiology and biotechnology , bone morphogenetic protein , biology , morphogen , paracrine signalling , chondrocyte , bone morphogenetic protein 4 , secretion , hedgehog signaling pathway , medicine , cartilage , endocrinology , signal transduction , anatomy , genetics , gene , receptor
Background The maturation of chondrocytes is essential for endochondral bone formation. The Indian Hedgehog ( Ihh ) gene is expressed in prehypertropic chondrocytes and has been proposed to regulate chondrocyte maturation. While such secretary factors as PTHrP and BMP are thought to be involved in Ihh expression, the mechanism of the restricted expression of Ihh is not clear. Results Using primary chondrocytes, we have developed here a modified micromass culture (MM‐C) system that allows the formation of concentration gradients of secreted factors, expressed either endogenously or retrovirally, from each of plural micromass cultures on a single plate. Using this system, we determined that chondrocytes create the inhibitory micro‐environment, partly dependent on PTHrP secretion, for the Ihh expression. We also showed that retrovirally induced BMP‐2 induces the expression of both Ihh and Noggin (encoding the BMP‐inactivating protein), and we further present evidence that a negative‐feedback loop involving Noggin might account for the precise localization of BMP signalling for Ihh induction. Conclusion These results suggest that the expression of the Ihh gene in cartilage is regulated by several mechanisms that include the secretion of inhibitory factors (including PTHrP) and the negative‐feed back loop formed by BMPs and Noggin.