Hyaluronic acid modulates gene expression of connective tissue growth factor (CTGF), transforming growth factor-β1 (TGF-β1), and vascular endothelial growth factor (VEGF) in human fibroblast-like synovial cells from advanced-stage osteoarthritis in vitro

Abstract

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 1 ) 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-b1 (TGFb1), 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-b1 and VEGF were significantly increased at the concentration of 0.1 mg/mL HA and 0.1 mg/mL Hylan, respectively (a < 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 (a < 0.05). We suggested that the profile of CTGF, TGF-b1, and VEGF gene expressions in our study might provide the rational mechanism for the therapeutic effect of hyaluronan on OA knees. ß

Intra-Articular Injections for the Treatment of Osteoarthritis

“…[58,59] VEGF induces capillary formation and is involved in the inflammatory process, while CTGF stimulates MMP-3 and cellular matrix degradation. [60–63] HA also inhibits IL-1β preventing MMP-1 and MMP-9 release, and it increases the cartilage catabolism of the joint.…”

Intra-Articular Injections for the Treatment of Osteoarthritis

“…In fact HA treatment decreases the expression of vascular endothelial growth factor (VEGF), VEGF receptor, and connective tissue growth factor (CTGF), which are known to be significantly upregulated in OA causing detrimental effects on cartilage. [58,59] VEGF induces capillary formation and is involved in the inflammatory process, while CTGF stimulates MMP-3 and cellular matrix degradation. [60][61][62][63] HA also inhibits IL-1b preventing MMP-1 and MMP-9 release, and it increases the cartilage catabolism of the joint.…”

Nitric oxide alters hyaluronan deposition by airway smooth muscle cells

“…Overexpression of HAS-2 in SMCs and myofibroblasts alters remodeling and hyper-reactivity in allergen-challenged mice[ 15 ]. Historically, the accumulation of HA has been viewed as simply a marker of inflammation, but the accumulation of HA may have many pathological consequences, including alteration of the biomechanical properties of the tissue, increasing the proliferation of SMCs[ 16 ], enhancing the production of transforming growth factor-beta (TGF-β)[ 17 ], modulating the effects of TGF-β[ 18 , 19 ], increasing the activation of tissue kallikrein[ 20 , 21 ], and modulation of leukocyte activity[ 4 , 22 , 23 ]. Circulating and sputum HA levels are potential biomarkers of asthma control[ 24 ], consistent with a role of HA in the pathogenesis of asthma[ 24 , 25 ].…”