Curcumin Inhibits Apoptosis of Chondrocytes through Activation ERK1/2 Signaling Pathways Induced Autophagy

Abstract

Osteoarthritis (OA) is an inflammatory disease of load-bearing synovial joints that is currently treated with drugs that exhibit numerous side effects and are only temporarily effective in treating pain, the main symptom of the disease. Consequently, there is an acute need for novel, safe, and more effective chemotherapeutic agents for the treatment of osteoarthritis and related arthritic diseases. Curcumin, the principal curcuminoid and the most active component in turmeric, is a biologically active phytochemical. Evidence from several recent in vitro studies suggests that curcumin may exert a chondroprotective effect through actions such as anti-inflammatory, anti-oxidative stress, and anti-catabolic activity that are critical for mitigating OA disease pathogenesis and symptoms. In the present study, we investigated the protective mechanisms of curcumin on interleukin 1β (IL-1β)-stimulated primary chondrocytes in vitro. The treatment of interleukin (IL)-1β significantly reduces the cell viability of chondrocytes in dose and time dependent manners. Co-treatment of curcumin with IL-1β significantly decreased the growth inhibition. We observed that curcumin inhibited IL-1β-induced apoptosis and caspase-3 activation in chondrocytes. Curcumin can increase the expression of phosphorylated extracellular signal-regulated kinases 1/2 (ERK1/2), autophagy marker light chain 3 (LC3)-II, and Beclin-1 in chondrocytes. The expression of autophagy markers could be decreased when the chondrocytes were incubated with ERK1/2 inhibitor U0126. Our results suggest that curcumin suppresses apoptosis and inflammatory signaling through its actions on the ERK1/2-induced autophagy in chondrocytes. We propose that curcumin should be explored further for the prophylactic treatment of osteoarthritis in humans and companion animals.

Polysaccharide from angelica sinensis attenuates SNP-Induced Apoptosis in osteoarthritis Chondrocytes by Inducing Autophagy via ERK1/2 Pathway

“…Shi et al showed that autophagy levels were signi cantly inhibited after activation of the p38 signaling pathway in osteoarthritis [40]. In addition, Li X et al reported that the ERK1/2 signaling pathways activation was involved in chondrocyte autophagy, which protected chondrocyte from apoptosis [41]. Moreover, Pathways such as AMPK/mTOR [42], PI3K/AKT [43], and AKT/mTOR [39] were associated with autophagy in chondrocytes.…”

Restoration of Autophagic Flux Rescues Oxidative Damage and Mitochondrial Dysfunction to Protect against Intervertebral Disc Degeneration

“…Because of its inherent anti-inflammatory, antioxidative stress, and anticatabolic properties, CUR can mitigate the pathogenesis and symptoms of various diseases, including osteoarthritis [20], Alzheimer's disease [21], and atherosclerosis [22]. Moreover, CUR has been recently demonstrated to induce autophagy in diverse tissues, such as cartilage [23], heart [24], and liver [25], but whether the NP is included among such tissues remains unknown. Given the established link between autophagy and oxidative stress and the ability of CUR to promote autophagy, an enhanced understanding of how CUR affects the NP might facilitate the development of clinically safe, orally available therapeutic agents for IDD.…”

Effects of tetrahedral framework nucleic acid/wogonin complexes on osteoarthritis

“…Treating OA is associated with high costs, 8 and its occurrence and progression are associated with various risk factors, such as aging, genetics, obesity, overuse, infection, and joint injury. 9,10 Cartilage is well known as an avascular connective tissue in which the sole cell type, the chondrocyte, obtains nutrition, and oxygen via diffusion from synovial fluid and subchondral bone. [11][12][13] Substantial evidence has revealed that chondrocyte apoptosis, chondrocyte phenotype loss, and synovial inflammation, which are characterized by the overproduction of pro-inflammatory mediators (including tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β) play a vital role in the occurrence and progression of OA, particularly in the early stages.…”