MicroRNA variants as genetic determinants of bone mass

• Published in: Bone (New York, N.Y.) Vol. 84; pp. 57 - 68
• Main Authors: Dole, Neha S, Delany, Anne M
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2016
• Subjects: Bone Density - genetics; Bone Diseases - genetics; Humans; MicroRNAs - genetics; miRNA; Models, Genetic; Orthopedics; Osteoarthritis; Osteoblast; Osteoclast; Osteoporosis; Polymorphism, Single Nucleotide - genetics; SNP; GWAS; lncRNA; single nucleotide polymorphism; osteoarthritis; Osteoclast; coding sequences; precursor microRNA; SLE; bone mineral density; Osteoporosis; MSCs; OA; systemic lupus erythematosus; UTR; CDS; SNP; BMD; long noncoding RNA; Osteoblast; DGCR8; genome wide association study; miRNA; pri-miRNA; RISC; TFBS; DiGeorge critical region 8; miR-SNPs; untranslated region; transcription factor binding site; RNA-induced silencing complex; microRNA gene SNPs; microRNA target site SNPs; MAF; minor allele frequency; primary microRNA; mesenchymal stem cells; microRNA; pre-miRNA; miR-TS-SNPs; miRNA, miR; Osteoarthritis
• ISSN: 8756-3282; 1873-2763
• DOI: 10.1016/j.bone.2015.12.016

Abstract Single nucleotide polymorphisms (SNPs) are the most abundant genetic variants that contribute to the heritability of bone mass. MicroRNAs (miRNAs, miRs) are key post-transcriptional regulators that modulate the differentiation and function of skeletal cells by targeting multiple genes in the same or distinct signaling pathways. SNPs in miRNA genes and miRNA binding sites can alter miRNA abundance and mRNA targeting. This review describes the potential impact of miRNA-related SNPs on skeletal phenotype. Although many associations between SNPs and bone mass have been described, this review is limited to gene variants for which a function has been experimentally validated. SNPs in miRNA genes (miR-SNPs) that impair miRNA processing and alter the abundance of mature miRNA are discussed for miR-146a, miR-125a, miR-196a, miR-149 and miR-27a. SNPs in miRNA targeting sites (miR-TS-SNPs) that alter miRNA binding are described for the bone remodeling genes bone morphogenetic protein receptor 1 (Bmpr1), fibroblast growth factor 2 (Fgf2), osteonectin (Sparc) and histone deacetylase 5 (Hdac5). The review highlights two aspects of miRNA-associated SNPs: the mechanism for altering miRNA mediated gene regulation and the potential of miR-associated SNPs to alter osteoblast, osteoclast or chondrocyte differentiation and function. Given the polygenic nature of skeletal diseases like osteoporosis and osteoarthritis, validating the function of additional miRNA-associated SNPs has the potential to enhance our understanding of the genetic determinants of bone mass and predisposition to selected skeletal diseases.