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Runx2 is required for chondrocyte proliferation and maturation. In the search of Runx2 target genes in chondrocytes, we found that Runx2 up-regulated the expression of hematopoietic cell kinase (<i>Hck)</i>, which is a member of the Src tyrosine kinase family, in chondrocytes, that <i>Hck</i> expression was high in cartilaginous limb skeletons of wild-type mice but low in those of <i>Runx2</i>^–/– mice, and that Runx2 bound the promoter region of <i>Hck</i>. To investigate the functions of Hck in chondrocytes, transgenic mice expressing a constitutively active form of <i>Hck</i> (<i>Hck</i>^CA) were generated using the <i>Col2a1</i> promoter/enhancer. The hind limb skeletons were fused, the tibia became a large, round mass, and the growth plate was markedly disorganized. Chondrocyte maturation was delayed until E16.5 but accelerated thereafter. BrdU-labeled, but not terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive, chondrocytes were increased. Furthermore, <i>Hck</i> knock-down reduced the proliferation of primary chondrocytes. In microarray and real-time RT-PCR analyses using hind limb RNA from <i>Hck</i>^CA transgenic mice, the expression of Wnt (<i>Wnt10b</i>, <i>Tcf7</i>, <i>Lef1</i>, <i>Dkk1</i>) and hedgehog (<i>Ihh</i>, <i>Ptch1</i>, and <i>Gli1</i>) signaling pathway genes was upregulated. These findings indicated that <i>Hck</i>, whose expression is regulated by Runx2, is highly expressed in chondrocytes, and that <i>Hck</i>^CA activates Wnt and hedgehog signaling pathways, and promotes chondrocyte proliferation without increasing apoptosis.