Deduction of Novel Genes Potentially Involved in Osteoblasts of Rheumatoid Arthritis Using Next-Generation Sequencing and Bioinformatic Approaches

Int J Mol Sci. 2017 Nov 11;18(11):2396. doi: 10.3390/ijms18112396.


The role of osteoblasts in peri-articular bone loss and bone erosion in rheumatoid arthritis (RA) has gained much attention, and microRNAs are hypothesized to play critical roles in the regulation of osteoblast function in RA. The aim of this study is to explore novel microRNAs differentially expressed in RA osteoblasts and to identify genes potentially involved in the dysregulated bone homeostasis in RA. RNAs were extracted from cultured normal and RA osteoblasts for sequencing. Using the next generation sequencing and bioinformatics approaches, we identified 35 differentially expressed microRNAs and 13 differentially expressed genes with potential microRNA-mRNA interactions in RA osteoblasts. The 13 candidate genes were involved mainly in cell-matrix adhesion, as classified by the Gene Ontology. Two genes of interest identified from RA osteoblasts, A-kinase anchoring protein 12 (AKAP12) and leucin rich repeat containing 15 (LRRC15), were found to express more consistently in the related RA synovial tissue arrays in the Gene Expression Omnibus database, with the predicted interactions with miR-183-5p and miR-146a-5p, respectively. The Ingenuity Pathway Analysis identified AKAP12 as one of the genes involved in protein kinase A signaling and the function of chemotaxis, interconnecting with molecules related to neovascularization. The findings indicate new candidate genes as the potential indicators in evaluating therapies targeting chemotaxis and neovascularization to control joint destruction in RA.

Keywords: bioinformatics; bone erosion; messenger RNA; microRNA; next-generation sequencing; osteoblasts; rheumatoid arthritis.

MeSH terms

  • Arthritis, Rheumatoid / genetics*
  • Base Sequence
  • Binding Sites / genetics
  • Bone and Bones / pathology
  • Cell-Matrix Junctions / metabolism
  • Computational Biology / methods*
  • Extracellular Matrix / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Gene Ontology
  • Gene Regulatory Networks
  • Genetic Association Studies
  • High-Throughput Nucleotide Sequencing / methods*
  • Humans
  • Joints / pathology
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Osteoblasts / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism


  • MicroRNAs
  • RNA, Messenger