J Bone Metab.  2016 Aug;23(3):121-127. 10.11005/jbm.2016.23.3.121.

Current Status and Strategy of microRNA Research for Cartilage Development and Osteoarthritis Pathogenesis

• Asahara H

• KMID: 2350807
• DOI: http://doi.org/10.11005/jbm.2016.23.3.121

Abstract

MicroRNAs (miRNAs), which are small (~21 nucleotides) non-coding RNAs, are important players in endochondral ossification, articular cartilage homeostasis, and arthritis pathogenesis. Comprehensive and genetic analyses of cartilage-specific or cartilage-related miRNAs have provided new information on cartilage development, homeostasis, and related diseases. State-of-the-art combinatorial approaches, including transcription-activator like effector nuclease (TALEN)/clustered regularly interspaced short palindromic repeats (CRISPR) technique for targeting miRNAs and high-throughput sequencing of RNA isolated by cross-linking immunoprecipitation for identifying target messenger RNAs, should be used to determine complex miRNA networks and miRNA-dependent cartilage regulation. Use of advanced drug delivery systems involving cartilage-specific miRNAs will accelerate the application of these new findings in arthritis therapy.

Keyword

Cartilage; Chondrocytes; MicroRNAs; Osteoarthritis

MeSH Terms

Arthritis
Cartilage*
Cartilage, Articular
Chondrocytes
Drug Delivery Systems
Homeostasis
Immunoprecipitation
MicroRNAs*
Osteoarthritis*
RNA
RNA, Messenger
RNA, Untranslated
MicroRNAs
RNA
RNA, Messenger
RNA, Untranslated

Figure

• 

  Fig. 1 MicroRNA (miRNA) synthesis and functions in chondrocytes. miRNAs are transcribed by specific transcription factors and processed by Drosha- and Dicer-mediated editing. A functional miRNA complex targets multiple messenger RNAs to regulate cartilage differentiation and homeostasis.

• 

  Fig. 2 MicroRNA (miRNA) molecular networks involved in chondrocyte differentiation and homeostasis. Each miRNA has specific target messenger RNAs and affect anabolic or catabolic signals in chondrocytes. MMP, matrix metalloproteinase; PDGFRα, platelet-derived growth factor receptors-alpha; IGFBP, insulin-like growth factor binding protein; Dnpep, aspartyl aminopeptidase; BMP, bone morphogenetic protein; TGF-β, transforming growth factor-beta.

• 

  Fig. 3 MicroRNA (miRNA) target site validation. Reporter assay is routinely performed to determine whether an messenger RNA is a direct functional target of an miRNA.

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