Research Paper Volume 13, Issue 8 pp 11281—11295

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

Renjie Xu1, *, , Fei Zhang2, *, , Junlan Lu3, , Kexin Wang3, , Peng Pan4, &, , Ye Sun5, &, , Yuxin Zhang6, &, ,

  • 1 Department of Rehabilitation Medicine, Kunshan Rehabilitation Hospital, Suzhou 215300, Jiangsu, People’s Republic of China
  • 2 Department of Orthopaedics, Huai’An People’s Hospital Of Hongze, Hongze 223100, Jiangsu Province, People’s Republic of China
  • 3 School of Kinesiology, Shanghai University of Sport, Yangpu 200438, Shanghai, People’s Republic of China
  • 4 Department of Anesthesiology, KunShan Hospital of Traditional Chinese Medicine, Kunshan 215300, Jiangsu, People’s Republic of China
  • 5 Department of Orthopaedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, People’s Republic of China
  • 6 Department of Rehabilitation Medicine, Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Huangpu 200011, Shanghai, People’s Republic of China
* Equal contribution

Received: November 20, 2020       Accepted: January 22, 2021       Published: April 4, 2021
How to Cite

Copyright: © 2021 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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.


DDH: Developmental dysplasia of the hip; FRZB: Frizzled-related protein; OA: osteoarthritis; SNP: Single nucleotide polymorphism; OR: Odd ratios; CI: confidence interval.