title: Expression of MicroRNA-146a in osteoarthritis cartilage.
abstract: OBJECTIVE
  A role of microRNA, which are approximately 22-nucleotide noncoding RNAs, has recently been recognized in human diseases. The objective of this study was to identify the expression pattern of microRNA-146a (miR-146a) in cartilage from patients with osteoarthritis (OA).
  
  
  METHODS
  The expression of miR-146a in cartilage from 15 patients with OA was analyzed by quantitative reverse transcription-polymerase chain reaction (RT-PCR) and by in situ hybridization. Induction of the expression of miR-146a by cultures of normal human articular chondrocytes following stimulation with interleukin-1beta (IL-1beta) was examined by quantitative RT-PCR.
  
  
  RESULTS
  All cartilage samples were divided into 3 groups according to a modification of the Mankin score (grade I = mild OA scored 0-5, grade II = moderate OA scored 6-10, and grade III = severe OA scored 11-14). In grade I OA cartilage samples, the expression of miR-146a and COL2A1 was significantly higher than that in the other groups (P < 0.05). In grades II and III OA cartilage, the expression of miR-146a and COL2A1 was decreased, whereas the expression of matrix metalloproteinase 13 (MMP-13) was elevated in grade II OA cartilage. These data showed that miR-146a is expressed intensely in cartilage with a low Mankin grade and that miR-146a expression decreases in parallel with the level of MMP-13 expression. Tissue section in situ hybridization of primary miR-146a (pri-miR-146a) revealed that pri-miR-146a was expressed in chondrocytes residing in all tissue layers, especially in the superficial layer, where it was intensely expressed. The expression of miR-146 was markedly elevated by IL-1beta stimulation in human chondrocytes in vitro.
  
  
  CONCLUSIONS
  This study shows that miR-146 is intensely expressed in low-grade OA cartilage and that its expression is induced by stimulation of IL-1beta. Thus, miR-146 might play a role in OA cartilage pathogenesis.
authors.affiliation: Hiroshima University, Hiroshima, Japan.
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Yamasaki
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Nakasa
authors.forename: Shigeru
authors.initials: S
authors.lastname: Miyaki
authors.forename: Masakazu
authors.initials: M
authors.lastname: Ishikawa
authors.forename: Masataka
authors.initials: M
authors.lastname: Deie
authors.forename: Nobuo
authors.initials: N
authors.lastname: Adachi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Yasunaga
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Asahara
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Ochi