title: Sox9 transcriptionally represses Spp1 to prevent matrix mineralization in maturing heart valves and chondrocytes.
abstract: Sox9 is an SRY-related transcription factor required for expression of cartilaginous genes in the developing skeletal system and heart valve structures. In contrast to positively regulating cartilaginous matrix, Sox9 also negatively regulates matrix mineralization associated with bone formation. While the transcriptional activation of Sox9 target genes during chondrogenesis has been characterized, the mechanisms by which Sox9 represses osteogenic processes are not so clear. Using ChIP-on-chip and luciferase assays we show that Sox9 binds and represses transactivation of the osteogenic glycoprotein Spp1. In addition, Sox9 knockdown in post natal mouse heart valve explants and rib chondrocyte cultures promotes Spp1 expression and matrix mineralization, while attenuating expression of cartilage genes Type II Collagen and Cartilage Link Protein. Further, we show that Spp1 is required for matrix mineralization induced by Sox9 knockdown. These studies provide insights into the molecular mechanisms by which Sox9 prevents pathologic matrix mineralization in tissues that must remain cartilaginous.
authors: Molecular and Cellular Pharmacology Graduate Program, Leonard M Miller School of Medicine, University of Miami, Miami, Florida, United States of America.
authors: Jacqueline D
authors: JD
authors: Peacock
authors: Danielle J
authors: DJ
authors: Huk
authors: Hasini N
authors: HN
authors: Ediriweera
authors: Joy
authors: J
authors: Lincoln
mesh_terms: D000818:Animals; D002114:Calcinosis / Q000209:etiology* / Q000517:prevention & control; D019902:Chondrocytes / Q000378:metabolism*; D020219:Chondrogenesis; D005109:Extracellular Matrix / Q000378:metabolism* / Q000473:pathology; D006351:Heart Valves / Q000378:metabolism*; D051379:Mice; D053495:Osteopontin / Q000037:antagonists & inhibitors* / Q000235:genetics; D012097:Repressor Proteins; D055758:SOX9 Transcription Factor / Q000502:physiology*; D014158:Transcription, Genetic
chemical_list: D012097:Repressor Proteins; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse; C506896:Spp1 protein, mouse; D053495:Osteopontin