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Secreted frizzled-related protein 3 was genetically and functionally associated with developmental dysplasia of the hip

Background: Developmental dysplasia of the hip (DDH) is the most common joint disease in child orthopedics. Secreted Frizzled-Related Protein 3 (FRZB) plays an important role in joint development. however, no direct association between FRZB and DDH has been demonstrated. Methods: Analysis of genotyp...

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Autores principales: Xu, Renjie, Zhang, Fei, Lu, Junlan, Wang, Kexin, Pan, Peng, Sun, Ye, Zhang, Yuxin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8109121/
https://www.ncbi.nlm.nih.gov/pubmed/33820867
http://dx.doi.org/10.18632/aging.202815
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author Xu, Renjie
Zhang, Fei
Lu, Junlan
Wang, Kexin
Pan, Peng
Sun, Ye
Zhang, Yuxin
author_facet Xu, Renjie
Zhang, Fei
Lu, Junlan
Wang, Kexin
Pan, Peng
Sun, Ye
Zhang, Yuxin
author_sort Xu, Renjie
collection PubMed
description Background: Developmental dysplasia of the hip (DDH) is the most common joint disease in child orthopedics. Secreted Frizzled-Related Protein 3 (FRZB) plays an important role in joint development. however, no direct association between FRZB and DDH has been demonstrated. Methods: Analysis of genotype distribution and allele frequency for detected single nucleotide polymorphisms (SNP) of FRZB was performed. FRZB expression was assayed in DDH joint tissues. Further experiments to identify the chondrogenic properties of FRZB were conducted. Potential upstream miRNAs for FRZB were assayed in DDH. Results: Significant difference in genotype distribution for rs3768842 (OR=1.46, P=0.0081) and rs2242040 (OR=0.65, P=0.0067) was found. DDH joint tissues showed significantly higher FRZB expression. FRZB demonstrated chondrogenic and anti-hypertrophic properties in vitro. FRZB modulated cell adhesion pathway and cell spreading by regulating integrins expressions. Upstream miRNAs regulating FRZB expression were identified in DDH synovial fluid. Experiments indicated that downregulated miRNA-454 caused FRZB upregulation in DDH joint. Conclusion: Dysregulated FRZB and its loci were associated with DDH. As a Wnt antagonist with chondrogenic properties, FRZB modulated cell adhesion pathway and cell spreading by regulating integrins expressions. FRZB in multiple DDH joint tissues might be mediated by the dysregulated miRNA expression profiles in the joint synovial fluid.
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spelling pubmed-81091212021-05-12 Secreted frizzled-related protein 3 was genetically and functionally associated with developmental dysplasia of the hip Xu, Renjie Zhang, Fei Lu, Junlan Wang, Kexin Pan, Peng Sun, Ye Zhang, Yuxin Aging (Albany NY) Research Paper Background: Developmental dysplasia of the hip (DDH) is the most common joint disease in child orthopedics. Secreted Frizzled-Related Protein 3 (FRZB) plays an important role in joint development. however, no direct association between FRZB and DDH has been demonstrated. Methods: Analysis of genotype distribution and allele frequency for detected single nucleotide polymorphisms (SNP) of FRZB was performed. FRZB expression was assayed in DDH joint tissues. Further experiments to identify the chondrogenic properties of FRZB were conducted. Potential upstream miRNAs for FRZB were assayed in DDH. Results: Significant difference in genotype distribution for rs3768842 (OR=1.46, P=0.0081) and rs2242040 (OR=0.65, P=0.0067) was found. DDH joint tissues showed significantly higher FRZB expression. FRZB demonstrated chondrogenic and anti-hypertrophic properties in vitro. FRZB modulated cell adhesion pathway and cell spreading by regulating integrins expressions. Upstream miRNAs regulating FRZB expression were identified in DDH synovial fluid. Experiments indicated that downregulated miRNA-454 caused FRZB upregulation in DDH joint. Conclusion: Dysregulated FRZB and its loci were associated with DDH. As a Wnt antagonist with chondrogenic properties, FRZB modulated cell adhesion pathway and cell spreading by regulating integrins expressions. FRZB in multiple DDH joint tissues might be mediated by the dysregulated miRNA expression profiles in the joint synovial fluid. Impact Journals 2021-04-04 /pmc/articles/PMC8109121/ /pubmed/33820867 http://dx.doi.org/10.18632/aging.202815 Text en Copyright: © 2021 Xu et al. https://creativecommons.org/licenses/by/3.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Xu, Renjie
Zhang, Fei
Lu, Junlan
Wang, Kexin
Pan, Peng
Sun, Ye
Zhang, Yuxin
Secreted frizzled-related protein 3 was genetically and functionally associated with developmental dysplasia of the hip
title Secreted frizzled-related protein 3 was genetically and functionally associated with developmental dysplasia of the hip
title_full Secreted frizzled-related protein 3 was genetically and functionally associated with developmental dysplasia of the hip
title_fullStr Secreted frizzled-related protein 3 was genetically and functionally associated with developmental dysplasia of the hip
title_full_unstemmed Secreted frizzled-related protein 3 was genetically and functionally associated with developmental dysplasia of the hip
title_short Secreted frizzled-related protein 3 was genetically and functionally associated with developmental dysplasia of the hip
title_sort secreted frizzled-related protein 3 was genetically and functionally associated with developmental dysplasia of the hip
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8109121/
https://www.ncbi.nlm.nih.gov/pubmed/33820867
http://dx.doi.org/10.18632/aging.202815
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