title: Identification of Elongated Primary Cilia with Impaired Mechanotransduction in Idiopathic Scoliosis Patients.
abstract: The primary cilium is an outward projecting antenna-like organelle with an important role in bone mechanotransduction. The capacity to sense mechanical stimuli can affect important cellular and molecular aspects of bone tissue. Idiopathic scoliosis (IS) is a complex pediatric disease of unknown cause, defined by abnormal spinal curvatures. We demonstrate significant elongation of primary cilia in IS patient bone cells. In response to mechanical stimulation, these IS cells differentially express osteogenic factors, mechanosensitive genes, and signaling genes. Considering that numerous ciliary genes are associated with a scoliosis phenotype, among ciliopathies and knockout animal models, we expected IS patients to have an accumulation of rare variants in ciliary genes. Instead, our SKAT-O analysis of whole exomes showed an enrichment among IS patients for rare variants in genes with a role in cellular mechanotransduction. Our data indicates defective cilia in IS bone cells, which may be linked to heterogeneous gene variants pertaining to cellular mechanotransduction.
authors.affiliation: Viscogliosi Laboratory in Molecular Genetics of Musculoskeletal Diseases, Sainte-Justine University Hospital Research Center, Montreal, Quebec, H3T 1C5, Canada.|Department of Biochemistry and Molecular Medicine, Faculty of Medicine, Université de Montreal, Montreal, Quebec, H3T 1J4, Canada.
authors.forename: Niaz
authors.initials: N
authors.lastname: Oliazadeh
authors.affiliation: Department of Biological Sciences, California State University, Chico, CA 95929, USA.
authors.forename: Kristen F
authors.initials: KF
authors.lastname: Gorman
authors.affiliation: Genome Quebec Innovation Center, McGill University, Montréal, Quebec, H3A 0G1, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Eveleigh
authors.affiliation: McGill University, Montréal, Quebec, H3A 1A4, Canada.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Bourque
authors.affiliation: Viscogliosi Laboratory in Molecular Genetics of Musculoskeletal Diseases, Sainte-Justine University Hospital Research Center, Montreal, Quebec, H3T 1C5, Canada.|Department of Biochemistry and Molecular Medicine, Faculty of Medicine, Université de Montreal, Montreal, Quebec, H3T 1J4, Canada.|Department of Stomatology, Faculty of Dentistry, Université de Montréal, Montreal, Quebec, H3T 1J4, Canada.
authors.forename: Alain
authors.initials: A
authors.lastname: Moreau
mesh_terms: D000293:Adolescent; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002923:Cilia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D059472:Exome; D005260:Female; D051518:Fibroblast Growth Factor 3 / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016547:Kinesins / Q000235:genetics / Q000378:metabolism; D040542:Mechanotransduction, Cellular / Q000235:genetics*; D010006:Osteoblasts / Q000378:metabolism* / Q000473:pathology; D010012:Osteogenesis / Q000235:genetics*; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism; D061251:Primary Cell Culture; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D012600:Scoliosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: C488660:ADGRG6 protein, human; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; C496444:FGF3 protein, human; D051518:Fibroblast Growth Factor 3; D018398:Homeodomain Proteins; C542809:LBX1 protein, human; C540807:POC5 protein, human; D051761:Paired Box Transcription Factors; D043562:Receptors, G-Protein-Coupled; D020825:T-Box Domain Proteins; C491182:TBX6 protein, human; D014157:Transcription Factors; C070835:PAX1 transcription factor; C096905:PTK7 protein, human; D020794:Receptor Protein-Tyrosine Kinases; C526774:KIF6 protein, human; D016547:Kinesins