Expression of MicroRNA‐146a in osteoarthritis cartilage

K Yamasaki, T Nakasa, S Miyaki… - … : Official Journal of …, 2009 - Wiley Online Library
K Yamasaki, T Nakasa, S Miyaki, M Ishikawa, M Deie, N Adachi, Y Yasunaga, H Asahara…
Arthritis & Rheumatism: Official Journal of the American College …, 2009Wiley Online Library
Objective A role of microRNA, which are∼ 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 …
Objective
A role of microRNA, which are ∼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‐1β (IL‐1β) 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‐1β stimulation in human chondrocytes in vitro.
Conclusion
This study shows that miR‐146 is intensely expressed in low‐grade OA cartilage and that its expression is induced by stimulation of IL‐1β. Thus, miR‐146 might play a role in OA cartilage pathogenesis.
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