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Sox9 shown to be a key factor in skeletogenesis
Previous studies have suggested a role for the transcription factor Sox9 in generating the cartilage growth plate during chondrogenesis, but its precise function remains unclear. Dy et al. generated mice with Sox9 conditional null alleles and with a doxycycline-inducible Cre transgene inserted into the DNA of the differentiated chondrocytes which are involved in growth plate generation. Treatment of pregnant mice resulted in severely dwarfed offspring; their chondrocytes lost the ability to grow larger and their endochondral bones did not elongate. Sox9 is, conclude the authors, necessary for generating cell hypertrophy and for maintaining proliferation of columnar chondrocytes, both key requirements of functional growth plates.
At the molecular level, Sox9 tightly controls β-catenin signaling as well as expression of Runx2, ensuring that proliferation is maintained, but prehypertrophy does not occur. As a result, cells are able to acquire the mature osteoblast phenotype. In hypertrophic chondrocytes, Sox9 RNA acts with Mef2c to activate Col10a1, thus controlling differentiation in the growth plate.
Editor's comment: This study illustrates that Sox9 is a key regulator of skeletogenesis; it promotes columnar chondrocyte proliferation and prevents prehypertrophy by suppressing Runx2 and Mef2c expression. Sox9 then activates chondrocyte hypertrophy along with Mef2c, with suppression of osteoblast differentiation by inhibiting Runx2, Osx and Mef2c expression and Wnt signaling.
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