Involvement of SOX-9 and FGF-23 in RUNX-2 regulation in osteoarthritic chondrocytes
Timoklia Orfanidou
University of Thessaly, Medical School, Laboratory of Cytogenetics and Medical Genetics, Larissa, Greece
Institute of Biomedical Research and Technology, Molecular Biology, Larissa, Greece
These authors contributed equally.
Search for more papers by this authorDimitrios Iliopoulos
Institute of Biomedical Research and Technology, Molecular Biology, Larissa, Greece
These authors contributed equally.
Search for more papers by this authorKonstantinos N. Malizos
Institute of Biomedical Research and Technology, Molecular Biology, Larissa, Greece
University of Thessaly, Medical School, Department of Orthopaedics, Larissa, Greece
Search for more papers by this authorCorresponding Author
Aspasia Tsezou
University of Thessaly, Medical School, Laboratory of Cytogenetics and Medical Genetics, Larissa, Greece
Institute of Biomedical Research and Technology, Molecular Biology, Larissa, Greece
University of Thessaly, Medical School, Department of Biology, Larissa, Greece
Correspondence to: Aspasia TSEZOU, Associate Professor of Medical Genetics, University of Thessaly, Medical School, Department of Biology, 22 Papakyriazi str. 41 222 Larisa, Greece.Tel.: +30-2410-682557Fax: +302291025758 E-mail: [email protected]Search for more papers by this authorTimoklia Orfanidou
University of Thessaly, Medical School, Laboratory of Cytogenetics and Medical Genetics, Larissa, Greece
Institute of Biomedical Research and Technology, Molecular Biology, Larissa, Greece
These authors contributed equally.
Search for more papers by this authorDimitrios Iliopoulos
Institute of Biomedical Research and Technology, Molecular Biology, Larissa, Greece
These authors contributed equally.
Search for more papers by this authorKonstantinos N. Malizos
Institute of Biomedical Research and Technology, Molecular Biology, Larissa, Greece
University of Thessaly, Medical School, Department of Orthopaedics, Larissa, Greece
Search for more papers by this authorCorresponding Author
Aspasia Tsezou
University of Thessaly, Medical School, Laboratory of Cytogenetics and Medical Genetics, Larissa, Greece
Institute of Biomedical Research and Technology, Molecular Biology, Larissa, Greece
University of Thessaly, Medical School, Department of Biology, Larissa, Greece
Correspondence to: Aspasia TSEZOU, Associate Professor of Medical Genetics, University of Thessaly, Medical School, Department of Biology, 22 Papakyriazi str. 41 222 Larisa, Greece.Tel.: +30-2410-682557Fax: +302291025758 E-mail: [email protected]Search for more papers by this authorAbstract
Chondrocytes’ hypertrophy includes metabolic changes, matrix remodelling, proliferation and apoptosis, characteristics associated with the progression of osteoarthritis. We investigated a possible association among Runt-related transcription factor 2 (RUNX-2), SOX-9 and fibroblast growth factor (FGF)-23 mRNA expressions in articular chondrocytes in order to elucidate their contribution in the osteoarthritic hypertrophic cartilage. SOX-9, FGF-23, RUNX-2 and matrix metalloproteinase (MMP)-13 mRNA expressions were evaluated in osteoarthritic and normal chondrocytes by real-time PCR whereas MMP-13 protein expression by immunofluorescense. RUNX-2, FGF-23 and SOX-9 were down-regulated using small interfering RNA technology and transfection with liposomes. The effect of human recombinant FGF-23 (hrFGF-23) on SOX-9 and RUNX-2 expression was tested in normal chondrocytes. We found higher expression of RUNX-2 and FGF-23 and a decreased expression of SOX-9 mRNA in osteoarthritic chondrocytes compared to normal (P < 0.0001). RUNX-2 down-regulation resulted in reduced MMP-13 expression in osteoarthritic chondrocytes and inhibition of SOX-9 in increased RUNX-2 and MMP-13 mRNA expression in normal chondrocytes, whereas inhibition of FGF-23 resulted in reduced RUNX-2 mRNA expression in osteoarthritic chondrocytes (all P < 0.0001). Silencing of RUNX-2 or FGF-23 did not affect SOX-9 mRNA levels in osteoarthritic chondrocytes. Moreover simultaneous down-regulation of SOX-9 and up-regulation of FGF-23 mRNA expressions in normal chondrocytes resulted in additive up-regulation of RUNX-2 mRNA expression. Treatment of normal chondrocytes with hrFGF-23 resulted in increased RUNX-2 mRNA expression, whereas it had no effect on SOX-9 mRNA expression. We demonstrated convincing associations among RUNX-2, SOX-9 and FGF-23 in relation to MMP-13 expression in osteoarthritic chondrocytes, contributing to a better understanding of the abnormal gene expression and cartilage degeneration processes associated with osteoarthritis.
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