Alleviation of Cartilage Destruction by Sinapic Acid in Experimental Osteoarthritis

Abstract

Sinapic acid (SA) modulates the nuclear factor-erythroid 2-related factor 2 (Nrf2) signaling pathway in chondrocytes. In order to test the hypothesis that SA is protective against the development of osteoarthritis (OA), primary mouse chondrocytes were treated in vitro with SA and the promoter transactivation activity of heme oxygenase 1 (HO-1), nuclear translocation of Nrf2, and protein expression of HO-1 were assayed. To test the hypothesis in vivo, a destabilization of the medial meniscus (DMM) model was used to induce OA in the knees of mice and SA was delivered orally to the experimental group. The chondrocytes were harvested for further analysis. The expression of HO-1 was similarly upregulated in cartilage from both the experimental mice and human chondrocytes from osteoarthritic knees. SA was found to enhance the promoter transactivation activity of heme oxygenase 1 (HO-1) and increase the expression of Nrf2 and HO-1 in primary chondrocytes. Histopathologic scores showed that the damage induced by the DMM model was significantly lower in the SA treatment group. The addition of a HO-1 inhibitor with SA did not show additional benefit over SA alone in terms of cartilage degradation or histopathologic scores. The expression of TNF-α, IL-1β, IL-6, MMP-1, MMP-3, MMP-13, ADAMTS4, and ADAMTS5 was significantly reduced both in vitro and in vivo by the presence of SA. Protein expressions of HO-1 and Nrf2 were substantially increased in knee cartilage of mice that received oral SA. Our results suggest that SA should be further explored as a preventative treatment for OA.

Antiarthritic Potential of Comprehensively Standardized Extract of Alternanthera bettzickiana: In Vitro and In Vivo Studies

“…Sinapic acid possesses anti-inflammatory effects through subduing manifestation of COX-2, iNOS, and TNF-α. 28 Chlorogenic acid (CA) is a polyphenol. Various studies have shown that CA exhibits different pharmacological effects like immunoprotective, anti-inflammatory, and antibacterial activities.…”

Pharmacological Targeting of Heme Oxygenase-1 in Osteoarthritis

“…Given its antioxidant properties, several studies have suggested a protective role of HO-1 in OA pathogenesis. It has been reported that HO-1 is significantly upregulated in human and mouse models of OA, with higher levels of expression being observed in areas of cartilage damage [ 120 , 121 ]. However, discrepancies exist regarding Nrf2/HO-1 expression between OA cartilage and IL-1β-induced OA-like chondrocytes [ 122 , 123 ].…”

Coniferaldehyde prevents articular cartilage destruction in a murine model via Nrf2/HO‑1 pathway

“…Although there was no significant statistical difference in the expression of both Nrf2 and HO-1 between the OA/CFA group and the Control/CFA group (may be due to the limited number of samples), it was speculated that the level of HO-1, a member of heat shock protein (HSP) family, which is produced by cells in response to exposure to stressful conditions, may be much higher in the OA/CFA group compared with the Control/CFA group. In our previous study, it was found that the level of HO-1 in knee cartilage significantly increased in both patients with OA and DMM-induced OA mice relative to controls, which may be regarded as a beneficial adaptive response to oxidative stress in chondrocytes during the progression of OA ( 20 ). These findings suggested that the development of OA also contributed to the increased expression of HO-1 in the OA/CFA group, and the very obvious upregulation of HO-1 induced by CFA may play a key role in delaying the progression of OA.…”

“…HO degrades heme to free iron, biliverdin and carbon monoxide ( 21 ). The authors previously reported that HO-1 expression is increased in cartilage from patients diagnosed with OA, which is regarded as an adaptive response against stress during cartilage damage ( 20 ). The induction of HO-1 suppresses the IL-1-induced expression of MMPs and inflammatory factors ( 22 , 23 ), which are abnormally enhanced in OA-affected cartilage.…”