Globular Adiponectin Attenuated H2O2-Induced Apoptosis in Rat Chondrocytes by Inducing Autophagy Through the AMPK/ mTOR Pathway

Abstract

Background/Aims: Chondrocyte apoptosis is closely related to the development and progression of osteoarthritis. Global adiponectin (gAPN), secreted from adipose tissue, possesses potent anti-inflammatory and antiapoptotic properties in various cell types. This study aimed to investigate the role of autophagy induced by gAPN in the suppression of H 2 O 2 -induced apoptosis and the potential mechanism of gAPN-induced autophagy in chondrocytes. Methods: H 2 O 2 was used to induce apoptotic injury in rat chondrocytes. CCK-8 assay was performed to determine the viability of cells treated with different concentrations of gAPN with or without H 2 O 2 . Cell apoptosis was detected by flow cytometry and TUNEL staining. Mitochondrial membrane potential was examined using JC-1 fluorescence staining assay. The autophagy inhibitors 3-MA and Bafilomycin A1 were used to treat cells and then evaluate the effect of gAPN-induced autophagy. To determine the downstream pathway, chondrocytes were preincubated with the AMPK inhibitor Compound C. Beclin-1, LC3B, P62 and apoptosisrelated proteins were identified by Western blot analysis. Results: H 2 O 2 (400 μM)-induced chondrocytes apoptosis and caspase-3 activation were attenuated by gAPN (0.5 μg/mL). gAPN increased Bcl-2 expression and decreased Bax expression. The loss of mitochondrial membrane potential induced by H 2 O 2 was also abolished by gAPN. Furthermore, the antiapoptotic effect of gAPN was related to gAPN-induced autophagy by increased formation of Beclin-1 and LC3B and P62 degradation. In particular, the inhibition of gAPN-induced autophagy by 3-MA prevented the protective effect of gAPN on apoptosis induced by H 2 O 2 . Moreover, gAPN increased p-AMPK expression and decreased p-mTOR expression. Compound C partly suppressed the expression of autophagy-related proteins and restored the expression of p-mTOR suppressed by gAPN. Thus, the AMPK/mTOR pathway played an important role

Multifaceted Physiological Roles of Adiponectin in Inflammation and Diseases

“…Globular adiponectin suppressed LPS-primed inflammasome activation by stimulating AMPK signaling pathways [140]. Additionally, rat chondrocyte was protected from apoptosis by globular adiponectin-induced AMPK-mTOR signaling [141].…”

Hyaluronic Acid Loaded with Cerium Oxide Nanoparticles as Antioxidant in Hydrogen Peroxide Induced Chondrocytes Injury: An In Vitro Osteoarthritis Model

“…Chondrocyte apoptosis is closely related to the development and progression of osteoarthritis. A previous study has demonstrated that H 2 O 2 can induce chondrocytes apoptosis and caspase-3 activation in rat chondrocytes [ 43 ]. In the study, both HA and CeO 2 nanoparticles could lower chondrocytes apoptosis induced by H 2 O 2 .…”

Dexmedetomidine alleviated neuropathic pain in dorsal root ganglion neurons by inhibition of anaerobic glycolysis activity and enhancement of ROS tolerance

“…In addition, a number of studies have revealed that ROS was involved in the apoptosis related to these conditions [40,41]. Other researchers have also demonstrated that low concentrations of H 2 O 2 can induce apoptosis in a variety of cells [42,43]. In addition, research has also found that dexmedetomidine exhibits an anti-oxidative stress effect by significantly inhibiting the excessive production of ROS.…”