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 and DDH has been demonstrated.

METHODS

Analysis of genotype distribution and allele frequency for detected single nucleotide polymorphisms (SNP) of was performed. expression was assayed in DDH joint tissues. Further experiments to identify the chondrogenic properties of were conducted. Potential upstream miRNAs for 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 expression. demonstrated chondrogenic and anti-hypertrophic properties . 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 and its loci were associated with DDH. As a Wnt antagonist with chondrogenic properties, 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.