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Osteoblast differentiation profiles define sex specific gene expression patterns in craniosynostosis.
Bone 2015; 76:169-76BONE

Abstract

Single suture craniosynostosis (SSC) is the premature fusion of one calvarial suture and occurs in 1-1700-2500 live births. Congenital fusion of either the sagittal, metopic, or coronal sutures represents 95% of all cases of SSC. Sagittal and metopic synostosis have a male preponderance (3:1) while premature fusion of the coronal suture has a female preponderance (2:1). Although environmental and genetic factors contribute to SSC, the etiology of the majority of SSC cases remains unclear. In this study, 227 primary calvarial osteoblast cell lines from patients with coronal, metopic, or sagittal synostosis and unaffected controls were established and assayed for ALP activity and BrdU incorporation (n = 226) as respective measures of early stage osteoblast differentiation and proliferation. Primary osteoblast cell lines from individuals with sagittal synostosis demonstrated higher levels of ALP activity and reduced proliferation when compared to control lines. In order to address the sex differences in SSC types, the data was further stratified by sex. Osteoblasts from males and females with sagittal synostosis as well as males with metopic synostosis demonstrated higher levels of ALP activity when compared to sex matched controls, and males with sagittal or metopic synostosis demonstrated reduced levels of proliferation. In order to elucidate genes and pathways involved in these observed phenotypes, correlation analyses comparing ALP activity and proliferation to global gene expression was performed. Transcripts related to osteoblast differentiation were identified both differentially up and downregulated, correlated with ALP activity when compared to controls, and demonstrated a striking sex specific gene expression pattern. These data support that the dysregulation of osteoblast differentiation plays a role in the development of SSC and that genetic factors contribute to the observed sex related differences.

Authors+Show Affiliations

Seattle Children's Research Institute, Center for Developmental Biology and Regenerative Medicine, Seattle, WA, USA.University of Washington, Center for Ecogenetics and Environmental Health, Seattle, WA, USA.Washington University, Department of Neurosurgery and St. Louis Children's Hospital, St. Louis, MO, USA.Seattle Children's Research Institute, Center for Developmental Biology and Regenerative Medicine, Seattle, WA, USA.Seattle Children's Research Institute, Center for Developmental Biology and Regenerative Medicine, Seattle, WA, USA.University of Washington, Center for Ecogenetics and Environmental Health, Seattle, WA, USA.School of Pharmacy, Pacific University, Hillsboro, OR, USA.Trialomics, Seattle, WA, USA.Seattle Children's Research Institute, Center for Developmental Biology and Regenerative Medicine, Seattle, WA, USA.Seattle Children's Research Institute, Center for Developmental Biology and Regenerative Medicine, Seattle, WA, USA; Seattle Children's Craniofacial Center, Seattle, WA, USA. Electronic address: mcunning@u.washington.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25753363

Citation

Park, Sarah S., et al. "Osteoblast Differentiation Profiles Define Sex Specific Gene Expression Patterns in Craniosynostosis." Bone, vol. 76, 2015, pp. 169-76.
Park SS, Beyer RP, Smyth MD, et al. Osteoblast differentiation profiles define sex specific gene expression patterns in craniosynostosis. Bone. 2015;76:169-76.
Park, S. S., Beyer, R. P., Smyth, M. D., Clarke, C. M., Timms, A. E., Bammler, T. K., ... Cunningham, M. L. (2015). Osteoblast differentiation profiles define sex specific gene expression patterns in craniosynostosis. Bone, 76, pp. 169-76. doi:10.1016/j.bone.2015.03.001.
Park SS, et al. Osteoblast Differentiation Profiles Define Sex Specific Gene Expression Patterns in Craniosynostosis. Bone. 2015;76:169-76. PubMed PMID: 25753363.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Osteoblast differentiation profiles define sex specific gene expression patterns in craniosynostosis. AU - Park,Sarah S, AU - Beyer,Richard P, AU - Smyth,Matthew D, AU - Clarke,Christine M, AU - Timms,Andrew E, AU - Bammler,Theo K, AU - Stamper,Brendan D, AU - Mecham,Brigham H, AU - Gustafson,Jennifer A, AU - Cunningham,Michael L, Y1 - 2015/03/07/ PY - 2014/11/25/received PY - 2015/02/18/revised PY - 2015/03/01/accepted PY - 2015/3/11/entrez PY - 2015/3/11/pubmed PY - 2016/2/27/medline KW - Craniosynostosis KW - Gene expression analysis KW - Osteoblast differentiation KW - Osteoblasts SP - 169 EP - 76 JF - Bone JO - Bone VL - 76 N2 - Single suture craniosynostosis (SSC) is the premature fusion of one calvarial suture and occurs in 1-1700-2500 live births. Congenital fusion of either the sagittal, metopic, or coronal sutures represents 95% of all cases of SSC. Sagittal and metopic synostosis have a male preponderance (3:1) while premature fusion of the coronal suture has a female preponderance (2:1). Although environmental and genetic factors contribute to SSC, the etiology of the majority of SSC cases remains unclear. In this study, 227 primary calvarial osteoblast cell lines from patients with coronal, metopic, or sagittal synostosis and unaffected controls were established and assayed for ALP activity and BrdU incorporation (n = 226) as respective measures of early stage osteoblast differentiation and proliferation. Primary osteoblast cell lines from individuals with sagittal synostosis demonstrated higher levels of ALP activity and reduced proliferation when compared to control lines. In order to address the sex differences in SSC types, the data was further stratified by sex. Osteoblasts from males and females with sagittal synostosis as well as males with metopic synostosis demonstrated higher levels of ALP activity when compared to sex matched controls, and males with sagittal or metopic synostosis demonstrated reduced levels of proliferation. In order to elucidate genes and pathways involved in these observed phenotypes, correlation analyses comparing ALP activity and proliferation to global gene expression was performed. Transcripts related to osteoblast differentiation were identified both differentially up and downregulated, correlated with ALP activity when compared to controls, and demonstrated a striking sex specific gene expression pattern. These data support that the dysregulation of osteoblast differentiation plays a role in the development of SSC and that genetic factors contribute to the observed sex related differences. SN - 1873-2763 UR - https://www.unboundmedicine.com/medline/citation/25753363/Osteoblast_differentiation_profiles_define_sex_specific_gene_expression_patterns_in_craniosynostosis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S8756-3282(15)00075-7 DB - PRIME DP - Unbound Medicine ER -