The postnatal role of Sox9 in cartilage.
Sox9 is an essential transcription factor for the differentiation of the chondrocytic lineage during embryonic development. To test whether Sox9 continues to play a critical role in cartilaginous tissues in the adult mice, we used an inducible, genetic strategy to disrupt the Sox9 gene postnatally in these tissues. The postnatal inactivation of Sox9 led to stunted growth characterized by decreased proliferation, increased cell death, and dedifferentiation of growth plate chondrocytes. Upon postnatal Sox9 inactivation in the articular cartilage, the sulfated proteoglycan and aggrecan content of the uncalcified cartilage were rapidly depleted and the degradation of aggrecan was accompanied by higher ADAMTS5 immunostaining and increased detection of the aggrecan neoepitope, NITEGE. In spite of the severe loss of Collagen 2a1 mRNA, the Collagen II protein persisted in the articular cartilage, and no histopathological signs of osteoarthritis were observed. The homeostasis of the intervertebral disk (IVD) was dramatically altered upon Sox9 depletion, resulting in disk compression and subsequent degeneration. Inactivation of Sox9 in the IVD markedly reduced the expression of several genes encoding extracellular matrix proteins, as well as some of the enzymes responsible for their posttranslational modification. Furthermore, the loss of Sox9 in the IVD decreased the expression of cytokines, cell-surface receptors, and ion channels, suggesting that Sox9 coordinates a large genetic program that is instrumental for the proper homeostasis of the cells contained in the IVD postnatally. Our results indicate that Sox9 has an essential role in the physiological control of cartilaginous tissues in adult mice. © 2012 American Society for Bone and Mineral Research.
Department of Genetics, The University of Texas M.D. Anderson Cancer Center; Houston, TX, USA. shenry@mdanderson.org
Stephen P
SP
Henry
Shoudan
S
Liang
Kadir C
KC
Akdemir
Benoit
B
de Crombrugghe
D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D024043:Collagen Type II / Q000378:metabolism; D006132:Growth Plate / Q000378:metabolism; D007403:Intervertebral Disc / Q000187:drug effects; D008297:Male; D051379:Mice; D010641:Phenotype; D055758:SOX9 Transcription Factor / Q000502:physiology*; D059467:Transcriptome
D024043:Collagen Type II; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse