Journal article
BBS9 gene in nonsyndromic craniosynostosis: Role of the primary cilium in the aberrant ossification of the suture osteogenic niche
Bone (New York, N.Y.), Vol.112, pp.58-70
07/2018
DOI: 10.1016/j.bone.2018.04.013
PMCID: PMC5970090
PMID: 29674126
Abstract
Nonsyndromic craniosynostosis (NCS) is the premature ossification of skull sutures, without associated clinical features. Mutations in several genes account for a small number of NCS patients; thus, the molecular etiopathogenesis of NCS remains largely unclear.
Our study aimed at characterizing the molecular signaling implicated in the aberrant ossification of sutures in NCS patients. Comparative gene expression profiling of NCS patient sutures identified a fused suture-specific signature, including 17 genes involved in primary cilium signaling and assembly. Cells from fused sutures displayed a reduced potential to form primary cilia compared to cells from control patent sutures of the same patient. We identified specific upregulated splice variants of the Bardet Biedl syndrome-associated gene 9 (BBS9), which encodes a structural component of the ciliary BBSome complex. BBS9 expression increased during in vitro osteogenic differentiation of suture-derived mesenchymal cells of NCS patients. Also, Bbs9 expression increased during in vivo ossification of rat sutures. BBS9 functional knockdown affected the expression of primary cilia on patient suture cells and their osteogenic potential. Computational modeling of the upregulated protein isoforms (observed in patients) predicted that their binding affinity within the BBSome may be affected, providing a possible explanation for the aberrant suture ossification in NCS.
•BBS9 expression is dysregulated in prematurely ossified sutures of craniosynostosis patients.•Primary cilium expression and signaling are abnormal in patient sutures' cells.•A specific BBS9 splice isoform is overexpressed in prematurely fused sutures.•The resulting BBS9 isoform may be unable to drive the correct assembly of the primary cilium.
Details
- Title: Subtitle
- BBS9 gene in nonsyndromic craniosynostosis: Role of the primary cilium in the aberrant ossification of the suture osteogenic niche
- Creators
- Marta Barba - Istituto di Anatomia Umana e Biologia Cellulare, Università Cattolica del Sacro Cuore, 00168 Rome, ItalyLorena Di Pietro - Istituto di Anatomia Umana e Biologia Cellulare, Università Cattolica del Sacro Cuore, 00168 Rome, ItalyLuca Massimi - Fondazione Policlinico Universitario “Agostino Gemelli”, 00168 Rome, ItalyMaria Concetta Geloso - Istituto di Anatomia Umana e Biologia Cellulare, Università Cattolica del Sacro Cuore, 00168 Rome, ItalyPaolo Frassanito - Fondazione Policlinico Universitario “Agostino Gemelli”, 00168 Rome, ItalyMassimo Caldarelli - Fondazione Policlinico Universitario “Agostino Gemelli”, 00168 Rome, ItalyFabrizio Michetti - Istituto di Anatomia Umana e Biologia Cellulare, Università Cattolica del Sacro Cuore, 00168 Rome, ItalyStefano Della Longa - Department of Life, Health and Environmental Sciences, University of L'Aquila, 67100, L'Aquila, ItalyPaul A Romitti - Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, 52242, IA, USAConcezio Di Rocco - Department of Neurosurgery, International Neuroscience Institute, 30625 Hannover, GermanyAlessandro Arcovito - Istituto di Neurochirurgia, Università Cattolica del Sacro Cuore, 00168 Rome, ItalyOrnella Parolini - Istituto di Anatomia Umana e Biologia Cellulare, Università Cattolica del Sacro Cuore, 00168 Rome, ItalyGianpiero Tamburrini - Fondazione Policlinico Universitario “Agostino Gemelli”, 00168 Rome, ItalyCamilla Bernardini - Istituto di Anatomia Umana e Biologia Cellulare, Università Cattolica del Sacro Cuore, 00168 Rome, ItalySimeon A Boyadjiev - Section of Genomics, Department of Pediatrics, University of California, 95817 Sacramento, CA, USAWanda Lattanzi - Istituto di Anatomia Umana e Biologia Cellulare, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
- Resource Type
- Journal article
- Publication Details
- Bone (New York, N.Y.), Vol.112, pp.58-70
- DOI
- 10.1016/j.bone.2018.04.013
- PMID
- 29674126
- PMCID
- PMC5970090
- NLM abbreviation
- Bone
- ISSN
- 8756-3282
- eISSN
- 1873-2763
- Publisher
- Elsevier Inc
- Grant note
- DOI: 10.13039/https://doi.org/10.13039/100000002, name: National Institutes of Health, award: R01 DE016886; name: Federazione GENE; DOI: 10.13039/https://doi.org/10.13039/501100005743, name: Università Cattolica del Sacro Cuore
- Language
- English
- Date published
- 07/2018
- Academic Unit
- Epidemiology; Biostatistics
- Record Identifier
- 9983996194702771
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