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By Clifford J Rosen; American Society for Bone and Mineral Research

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2003. Wnt5a and Wnt5b exhibit distinct activities in coordinating chondrocyte proliferation and differentiation. Development 130(5): 1003–1015. Akiyama H, Lyons JP, Mori-Akiyama Y, Yang X, Zhang R, Zhang Z, Deng JM, Taketo MM, Nakamura T, Behringer RR, McCrea PD, De Crombrugghe B. 2004. Interactions between Sox9 and β-catenin control chondrocyte differentiation. Genes Dev 18(9): 1072–1087. Dailey L, Laplantine E, Priore R, Basilico C. 2003. A network of transcriptional and signaling events is activated by FGF to induce chondrocyte growth arrest and differentiation.

In the absence of either canonical or noncanonical Wnt signaling, chondrocyte proliferation is altered and hypertrophy is delayed [63, 81, 82]. Furthermore, both canonical and noncanonical Wnt pathways act in parallel with Ihh signaling to regulate chondrocyte proliferation and differentiation [69, 81]. Wnt and Ihh signaling may regulate common downstream targets such as Sox9 (see below) [81, 82]. Many FGF ligands and receptors (FGFRs) are expressed in the developing cartilage. The significant role of FGF signaling in skeletal development was first realized by the discovery that achondroplasia (ACH, OMIM#100800), the most common form of skeletal dwarfism in humans, was caused by a missense mutation in FGFR3.

101. Yoshida CA, Yamamoto H, Fujita T, Furuichi T, Ito K, Inoue K, Yamana K, Zanma A, Takada K, Ito Y, Komori T. 2004. Runx2 and Runx3 are essential for chondrocyte maturation, and Runx2 regulates limb growth through induction of Indian hedgehog. Genes Dev 18(8): 952–963. 102. Hinoi E, Bialek P, Chen YT, Rached MT, Groner Y, Behringer RR, Ornitz DM, Karsenty G. 2006. Runx2 inhibits chondrocyte proliferation and hypertrophy through its expression in the perichondrium. Genes Dev 20(21): 2937–2942.

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