Integrative analysis reveals key mRNAs and lncRNAs in monocytes of osteoporotic patients

Math Biosci Eng. 2019 Jun 27;16(5):5947-5971. doi: 10.3934/mbe.2019298.

Abstract

Osteoporosis is the most common bone metabolic disease. Abnormal osteoclast formation and resorption play a fundamental role in osteoporosis pathogenesis. Recent researches have greatly broaden our understanding of molecular mechanisms of osteoporosis. However, the molecular mechanisms of key mRNAs and lncRNAs, and their interactions leading to osteoporosis are still not entirely clear. The purpose of this work is to study the key mRNAs and lncRNAs, and their interactions involved in bone mineral homeostasis and osteoclastogenesis. Systematic analyses such as differential expression analysis, GO and KEGG analysis, and PPI network construction revealed that up-regulated mRNAs were significantly enriched in inflammation-related pathways. Moreover, we observed that the down-regulated proteins, including JDP2, HADC4, HDAC5, CDYL2, ACADVL, ACSL1 and BRD4, were key components in the down-regulated PPI network, indicating that the downregulation of histone deacetylases and cofactors, such as, HDAC4, HDAC5 and JDP2 may be critical regulators in osteoclastogenesis. In addition, we also highlighted one lncRNA, RP11-498C9.17, was highly correlated with epigenetic regulators, such as HDAC4, MORF4L1, HMGA1 and DND1, indicating that the lncRNA RP11-498C9.17 may also be an epigenetic regulator. In conclusion, our integrative analysis reveals key mRNAs and lncRNAs, involved in bone mineral homeostasis and osteoclastogenesis, which not only broaden our insights into lncRNAs in bone mineral homeostasis and osteoclastogenesis, but also improve our understanding of molecular mechanism.

Keywords: Osteoporosis; key mRNAs and lncRNAs; molecular mechanism; osteoclastogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagy
  • Bone Remodeling
  • Epigenesis, Genetic*
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Homeostasis
  • Humans
  • Inflammation
  • Monocytes / metabolism*
  • Osteoblasts / metabolism
  • Osteoclasts / metabolism
  • Osteoporosis / metabolism*
  • Protein Interaction Mapping
  • RNA, Long Noncoding / metabolism*
  • RNA, Messenger / metabolism*
  • Signal Transduction
  • Up-Regulation

Substances

  • RNA, Long Noncoding
  • RNA, Messenger