Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
Regulation of the IGFBP-5 and MMP-13 Genes by the Micro RNAs Mir-140 and Mir-27a in Human Osteoarthritic Chondrocytes
Tardif1, Ginette, Hum1, David, Pelletier1, Jean-Pierre, Duval2, Nicolas, Martel-Pelletier1, Johanne
MMP-13 and IGFBP-5 are important factors involved in osteoarthritis (OA). We investigated the potential regulation of these two genes by microRNAs (miRNAs) in cultured human OA chondrocytes.
Gene expression was determined by real-time PCR. The effect of each miRNA on IGFBP-5 and MMP-13 expression/production was evaluated by transiently transfecting their precursors (pre-miRNAs) and inhibitors (anti-miRNAs) into human OA chondrocytes. Modulation of IGFBP-5, miR-140 and miR-27a expression was determined upon treatment of OA chondrocytes with cytokines and growth factors.
IGFBP-5 was expressed in cultured human chondrocytes with levels significantly (p<0.04) lower in OA. Computational algorithms identified miR-140 and miR-27a as possible regulators of MMP-13 and IGFBP-5 expression. Data showed that both miRNAs were expressed in chondrocytes. There was a significant (p<0.01) reduction in miR-140 expression in OA. Transfection with pre-miR-140 significantly (p<0.005) decreased IGFBP-5 expression at 24 hours, while pre-miR-27a did not affect either MMP-13 or IGFBP-5. Treatment with anti-miR-27a, but not with anti-miR-140, significantly increased the expression of both MMP-13 (p<0.05) and IGFBP-5 (p<0.01) but only after 72 hours incubation. These data indicate that IGFBP-5 is a direct target of miR-140, whereas miR-27a indirectly down-regulates both MMP-13 and IGFBP-5. TGF-b down-regulates miR-140 and up-regulates IGFBP-5.
Data revealed that miR-140 acted directly on decreasing IGFBP-5 expression but that miR-27a indirectly decreased both MMP-13 and IGFBP-5. Data from the study could be the first step in generating more comprehensive knowledge of the regulation of other MMPs and IGFBPs involved in OA, which could open up novel avenues in therapeutic strategies targeting this disease.
To cite this abstract, please use the following information:
Tardif, Ginette, Hum, David, Pelletier, Jean-Pierre, Duval, Nicolas, Martel-Pelletier, Johanne; Regulation of the IGFBP-5 and MMP-13 Genes by the Micro RNAs Mir-140 and Mir-27a in Human Osteoarthritic Chondrocytes [abstract]. Arthritis Rheum 2009;60 Suppl 10 :1910