Department of Rehabilitation Medicine, Kunshan Rehabilitation Hospital, Suzhou 215300, Jiangsu, People's Republic of China.
Department of Orthopaedics, Huai'An People's Hospital Of Hongze, Hongze 223100, Jiangsu Province, People's Republic of China.
Aging (Albany NY). 2021 Apr 4;13(8):11281-11295. doi: 10.18632/aging.202815.
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.
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.
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.
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.
发育性髋关节发育不良（DDH）是儿童矫形科最常见的关节疾病。分泌型卷曲相关蛋白 3（FRZB）在关节发育中起重要作用。然而，尚未证明与 DDH 之间存在直接关联。
分析了检测到的 FRZB 单核苷酸多态性（SNP）的基因型分布和等位基因频率。检测了 DDH 关节组织中的 FRZB 表达。进一步进行了鉴定 FRZB 软骨形成特性的实验。检测了 DDH 中 FRZB 的潜在上游 miRNA。
rs3768842（OR=1.46，P=0.0081）和 rs2242040（OR=0.65，P=0.0067）的基因型分布存在显著差异。DDH 关节组织显示 FRZB 表达显著升高。FRZB 表现出软骨形成和抗肥大特性。通过调节整合素表达，调节细胞黏附途径和细胞铺展。在 DDH 滑液中鉴定出调节 FRZB 表达的上游 miRNA。实验表明，下调的 miRNA-454 导致 DDH 关节中 FRZB 上调。
失调的 FRZB 及其基因座与 DDH 相关。作为具有软骨形成特性的 Wnt 拮抗剂，FRZB 通过调节整合素表达来调节细胞黏附途径和细胞铺展。多个 DDH 关节组织中的 FRZB 可能是由关节滑液中失调的 miRNA 表达谱介导的。
