MicroRNA-337 is associated with chondrogenesis through regulating TGFBR2 expression

Osteoarthritis Cartilage. 2012 Jun;20(6):593-602. doi: 10.1016/j.joca.2012.03.002. Epub 2012 Mar 14.

Abstract

Objective: MicroRNAs (miRNAs) have been implicated in regulating diverse cellular pathways and involved in development and inflammation. This study aimed to examine six miRNAs expression during the cartilage development and identify the key miRNA which is associated with chondrogenesis.

Methods: The expression of six miRNAs in cartilage tissue during development was screened by real-time quantitative polymerase chain reaction (RT-qPCR). Rat models of bone matrix gelatin induced endochondral ossification, collagen-induced arthritis and pristane-induced arthritis were established to examine whether miR-337 is involved in chondrogenesis. Furthermore, the regulation of transforming growth factor-b type II receptor (TGFBR2) expression by miR-337 was determined with the luciferase reporter gene assay and Western blot. The expression of some specific genes relevant to cartilage tissue was tested by RT-qPCR after miR-337 mimic or inhibitor transfection.

Results: MiR-337 expression was significantly down-regulated and almost disappeared in the maturation phases of endochondral ossification. The results of histology and RT-qPCR from three rat models showed that miR-337 is directly bound up with chondrogenesis. Furthermore, the results from the luciferase reporter gene assay and Western blot indicated that miR-337 regulated TGFBR2 expression. Our study also found that the enhancement of miR-337 may modulate the expression of cartilage-specific genes such as AGC1 in C-28/I2 chondrocytes.

Conclusion: We proved that miRNA-337 is associated with chondrogenesis through regulating TGFBR2 expression, and miRNA-337 can also influence cartilage-specific gene expression in chondrocytes. These findings may provide an important clue for further research in the arthritis pathogenesis and suggest a new remedy for arthritis treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Experimental / genetics
  • Arthritis, Experimental / metabolism
  • Cartilage, Articular / growth & development
  • Cartilage, Articular / metabolism
  • Cell Line
  • Chondrocytes / metabolism
  • Chondrogenesis / genetics*
  • Chondrogenesis / physiology
  • Down-Regulation / genetics
  • Female
  • Femur Head / growth & development
  • Gene Expression Profiling / methods
  • Gene Expression Regulation / genetics
  • Genes, Reporter
  • Humans
  • Male
  • MicroRNAs / metabolism
  • MicroRNAs / physiology*
  • Osteogenesis / genetics
  • Protein Serine-Threonine Kinases / biosynthesis*
  • Protein Serine-Threonine Kinases / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Real-Time Polymerase Chain Reaction / methods
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Transforming Growth Factor beta / biosynthesis*
  • Receptors, Transforming Growth Factor beta / genetics

Substances

  • MicroRNAs
  • Mirn337 microRNA, human
  • Receptors, Transforming Growth Factor beta
  • Protein Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type II