Core regulatory RNA molecules identified in articular cartilage stem/progenitor cells during osteoarthritis progression

  • Epigenomics. 2019 May;11(6):669-684. doi: 10.2217/epi-2018-0212.
Shuai Zhang  1 ,  Qier An  1 ,  Peilin Hu  1 ,  Xiaomin Wu  2 ,  Xiaohua Pan  2 ,  Wenjin Peng  1 ,  Rikang Wang  1 ,  Jingyi Gan  1 ,  Di Chen  3 ,  Zhen Li  4 ,  Tianfu Wang  5 ,  Guangqian Zhou  1
Affiliations
  • 1. Department of Medical Cell Biology & Genetics, Guangdong Key Laboratory of Genomic Stability & Disease Prevention, Shenzhen Key Laboratory of Anti-aging & Regenerative Medicine, & Shenzhen Engineering Laboratory of Regenerative Technologies for Orthopaedic Diseases, Health Sciences Center, Shenzhen University, Shenzhen 518060, PR China.
  • 2. Department of Orthopedic & Traumatology, Shenzhen BaoAn People Hospital Affiliated Southern Medical University, Shenzhen, Guangdong 518101, PR China.
  • 3. Department of Orthopedic Surgery, Rush University Medical Center, Chicago, IL 60612, USA.
  • 4. Shenzhen Alps Cell Sci-Tech Co. Ltd, Longhua District, Shenzhen, PR China.
  • 5. Guangdong Key Laboratory for Biomedical Measurements & Ultrasound Imaging, School of Biomedical Engineering, Health Sciences Center, Shenzhen University, Shenzhen 518060, PR China.
PMID: 30775942 DOI: 10.2217/epi-2018-0212
Abstract

Aim: To assess cartilage-derived stem/progenitor cells (CSPCs) in Osteoarthritis (OA) by employing mRNA-miRNA-circRNA-lncRNA network biology approach. Methods: Differentially expressed (DE) RNAs in CSPCs from 2-/4-/8-month-old STR/Ort and CBA mice were identified to construct networks via RNA Sequencing. Results: Compared with age-matched CBA mice, 4-/8-month-old STR/Ort mice had cartilage lesions and their CSPCs exhibited lower proliferative and differentiation capacity (decreased CD44 and CD90), and identified 7082 DE RNAs in STR/Ort mice were associated with strain differences or OA progression. OA-related core RNAs were identified via the networks constructed with the predominant DE RNAs, which were involved in the signaling pathways (NF-κB/MAPK/Hippo/Wnt/TGF-β/Cytoskeleton organization). The core RNAs (miR-322-5p/miR-493-5p/miR-378c/CPNE1/Cdh2/PRDM16/CTGF/NCAM1) were validated in CSPCs from OA patients. Conclusion: RNA-based networks identifying core RNAs and signaling pathways contribute to CSPC-dependent OA mechanisms.

Keywords
RNA-sequencing; STR/Ort mice; cartilage; circRNA; lncRNA; mRNA; miRNA; noncoding RNAs; osteoarthritis; proliferation; stem/progenitor cells.
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