Hyaluronic acid modulates gene expression of connective tissue growth factor (CTGF), transforming growth factor-beta1 (TGF-beta1), and vascular endothelial growth factor (VEGF) in human fibroblast-like synovial cells from advanced-stage osteoarthritis in vitro.
Intraarticular injection of hyaluronan (hyaluronic acid; HA) is the common way to treat osteoarthritis (OA) of knees. This treatment cannot only maintain the viscoelastic properties of knee but also release the OA pain. However, the exact molecular mechanism is unknown. In this study, after human synovial cells were stimulated with HA and Hylan (Synvisc) for 24 h, real-time polymerase chain reaction (real-time PCR) was used to detect the alteration of connective tissue growth factor (CTGF), transforming growth factor-beta1 (TGF-beta1), and vascular endothelial growth factor (VEGF) gene expression, which were specific genes related to pathogenesis of OA knees. Our results illustrated that both HA and Hylan might not cause cytotoxicity or apoptosis of synovial cells in serum deprivation environment. The gene expressions of TGF-beta1 and VEGF were significantly increased at the concentration of 0.1 mg/mL HA and 0.1 mg/mL Hylan, respectively (alpha < 0.05). The synovial cells with treatment of 0.1 mg/mL Hylan decreased the CTGF gene expression (0.66-fold) and VEGF (0.78-fold) compared to 0.1 mg/mL HA (alpha < 0.05). We suggested that the profile of CTGF, TGF-beta1, and VEGF gene expressions in our study might provide the rational mechanism for the therapeutic effect of hyaluronan on OA knees.
Lee
Yu-Tsang
YT
Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, No. 1, Jen Ai Road, Sec 1, Taipei, 100, Taiwan, Republic of China.
Shao
Hung-Jen
HJ
Wang
Jyh-Horng
JH
Liu
Haw-Chang
HC
Hou
Sheng-Mou
SM
Young
Tai-Horng
TH
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000368:Aged; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D055513:Connective Tissue Growth Factor / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D006801:Humans; D006820:Hyaluronic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D008856:Microscopy, Fluorescence; D020370:Osteoarthritis, Knee / Q000473:pathology* / Q000601:surgery; D011859:Radiography; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D053773:Transforming Growth Factor beta1 / Q000235:genetics* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
D000276:Adjuvants, Immunologic; C526317:CCN2 protein, human; D053773:Transforming Growth Factor beta1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C049816:hylan; D055513:Connective Tissue Growth Factor; D006820:Hyaluronic Acid