title: SOXC Genes and the Control of Skeletogenesis.
abstract: The SOXC group of transcription factors, composed of SOX4, SOX11, and SOX12, has evolved to fulfill key functions in cell fate determination. Expressed in many types of progenitor/stem cells, including skeletal progenitors, SOXC proteins potentiate pathways critical for cell survival and differentiation. As skeletogenesis unfolds, SOXC proteins ensure cartilage primordia delineation by amplifying canonical WNT signaling and antagonizing the chondrogenic action of SOX9 in perichondrium and presumptive articular joint cells. They then ensure skeletal elongation by inducing growth plate formation via enabling non-canonical WNT signaling. Human studies have associated SOX4 with bone mineral density and fracture risk in osteoporotic patients, and SOX11 with Coffin-Siris, a syndrome that includes skeletal dysmorphism. Meanwhile, in vitro and mouse studies have suggested important cell-autonomous roles for SOXC proteins in osteoblastogenesis. We here review current knowledge and gaps in understanding of SOXC protein functions, with an emphasis on the skeleton and possible links to osteoporosis.
authors.affiliation: Department of Cellular & Molecular Medicine, Orthopaedic and Rheumatologic Research Center, Cleveland Clinic Lerner Research Institute, 9500 Euclid Avenue, Cleveland, OH, 44195, USA. lefebvv@ccf.org.
authors.forename: Véronique
authors.initials: V
authors.lastname: Lefebvre
authors.affiliation: Department of Cellular & Molecular Medicine, Orthopaedic and Rheumatologic Research Center, Cleveland Clinic Lerner Research Institute, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.
authors.forename: Pallavi
authors.initials: P
authors.lastname: Bhattaram
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics; D000818:Animals; D015519:Bone Density / Q000235:genetics; D001846:Bone Development / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics; D020219:Chondrogenesis / Q000235:genetics*; D005145:Face / Q000002:abnormalities; D006228:Hand Deformities, Congenital / Q000235:genetics; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D051379:Mice; D008844:Micrognathism / Q000235:genetics; D009333:Neck / Q000002:abnormalities; D010006:Osteoblasts; D058866:Osteoporotic Fractures / Q000235:genetics; D055758:SOX9 Transcription Factor / Q000235:genetics; D055751:SOXC Transcription Factors / Q000235:genetics*; D013234:Stem Cells; D060449:Wnt Signaling Pathway / Q000235:genetics
chemical_list: C097473:SOX11 protein, human; C107423:SOX12 protein, human; C083431:SOX4 protein, human; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; D055751:SOXC Transcription Factors
keywords: Bone; Cartilage; Cell fate; Progenitor/stem cell; SOXC; Transcription
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