Three functional polymorphisms in CCDC170 were associated with osteoporosis phenotype
Xinhong Liu1,2,3,4, Yu-Gang Li5, Fang Tan6
1Chongqing Collaborative Innovation Center for Functional Food, Chongqing University of Education, Chongqing 400067, China.
Biology Open
|March 31, 2021
Summary
CCDC170 positively regulates bone formation. Specific microRNAs (miRNAs) inhibit CCDC170 expression by binding to genetic variations, impacting osteoporosis risk and offering potential therapeutic targets.
Area of Science:
- Genetics
- Molecular Biology
- Bone Biology
Background:
- MicroRNAs (miRNAs) are crucial regulators of bone formation and homeostasis.
- Genetic variations in miRNA target sites are linked to osteoporosis risk.
- The role of CCDC170 in bone metabolism remains largely unknown.
Purpose of the Study:
- To elucidate the function of CCDC170 in bone biology.
- To identify specific miRNAs that target CCDC170.
- To investigate the impact of genetic variations on miRNA-mediated CCDC170 regulation and osteoporosis susceptibility.
Main Methods:
- CCDC170 was knocked down in cellular and mouse models.
- Bioinformatic databases (TargetScan, miRNASNP, miRBase) were used to identify miRNA recognition sites within CCDC170.
- The allele-specific binding of miRNAs to CCDC170, influenced by GWAS lead SNPs, was analyzed.
Main Results:
- CCDC170 was confirmed to play a significant role in promoting bone formation.
- Five miRNAs (miR-153-3p, miR-374b-3p, miR-4274, miR-572, miR-2964a-5p) were found to inhibit CCDC170 expression.
- This inhibition occurred in an allele-specific manner, mediated by the binding of these miRNAs to GWAS lead SNPs (rs6932603, rs3757322, rs3734806).
Conclusions:
- CCDC170 is a positive regulator of bone formation.
- Specific miRNAs and their interaction with common genetic variants (GWAS SNPs) influence CCDC170 expression and potentially osteoporosis pathogenesis.
- These findings highlight a novel pathway involving CCDC170, miRNAs, and genetic variations, offering potential therapeutic targets for osteoporosis.
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