Resveratrol and Curcumin AttenuateEx VivoSugar-Induced Cartilage Glycation, Stiffening, Senescence, and Degeneration

Abstract

Objective Advanced glycation end-product (AGE) accumulation is implicated in osteoarthritis (OA) pathogenesis in aging and diabetic populations. Here, we develop a representative nonenzymatic glycation-induced OA cartilage explant culture model and investigate the effectiveness of resveratrol, curcumin, and eugenol in inhibiting AGEs and the structural and biological hallmarks of cartilage degeneration. Design Bovine cartilage explants were treated with AGE–bovine serum albumin, threose, and ribose to determine the optimal conditions that induce physiological levels of AGEs while maintaining chondrocyte viability. AGE crosslinks, tissue stiffness, cell viability, metabolism and senescence, nitrite release and loss of glycosaminoglycans were assessed. Explants were cotreated with resveratrol, curcumin, or eugenol to evaluate their anti-AGE properties. Blind docking analysis was conducted to estimate binding energies of drugs with collagen II. Results Treatment with 100 mM ribose significantly increased AGE crosslink formation and tissue stiffness, resulting in reduced chondrocyte metabolism and enhanced senescence. Blind docking analysis revealed stronger binding energies of both resveratrol and curcumin than ribose, with glycation sites along a human collagen II fragment, indicating their increased likelihood of competitively inhibiting ribose activity. Resveratrol and curcumin, but not eugenol, successfully inhibited AGE crosslink formation and its associated downstream biological response. Conclusions We establish a cartilage explant model of OA that recapitulates several aspects of aged human cartilage. We find that resveratrol and curcumin are effective anti-AGE therapeutics with the potential to decelerate age-related and diabetes-induced OA. This in vitro nonenzymatic glycation-induced model provides a tool for screening OA drugs, to simultaneously evaluate AGE-induced biological and mechanical changes.

Curcumin Alleviates LPS-Induced Oxidative Stress, Inflammation and Apoptosis in Bovine Mammary Epithelial Cells via the NFE2L2 Signaling Pathway

“…We believe this is related to CUR's promotion of cell growth and metabolism. For example, in the study of Mehta and Shikhar et al, CUR increased chondrocytes viability of the cell [24]. In addition, CUR can significantly improve the decrease in cell viability and cell damage caused by LPS.…”

Single-Dose Intra-Cartilage Delivery of Kartogenin Using a Cationic Multi-Arm Avidin Nanocarrier Suppresses Cytokine-Induced Osteoarthritis-Related Catabolism

“…Cartilage explants harvested from 1- to 2–week-old calf knee joints (procured from Research 87, Boylston, MA) were equilibrated separately in culture media for 2 days prior to treatment as described previously. 40 - 42 Cartilage explants were then treated with or without a combination of cytokines, Oncostatin M (OSM) (3 ng/ml) + IL-1α (2 ng/ml), for 8 days in combination with (1) a single dose of 100 μM free KGN, (2) a continuous dose of 100 μM free KGN, (3) a single dose of mAv-OH-KGN (100 μM KGN), or (4) a single dose of mAv-NH-KGN (100 μM KGN). Media was changed every 2 days and the cytokine combination (OSM + IL-1α) was replenished at each medium change.…”

“…After 8 days of culture, cartilage explants were weighed and digested in proteinase K as previously described. 39 , 40 , 42 The cumulative GAGs released to the media and residual GAGs in the digested explants were measured using the 1,9-dimethylmethylene blue (DMMB) assay. 46 Nitrite content was measured using the Griess assay as an indicator of nitric oxide (NO) release from tissues.…”

Cationic peptide carriers enable long-term delivery of insulin-like growth factor-1 to suppress osteoarthritis-induced matrix degradation

“…Initially, full-thickness plugs were extracted from the femoropatellar grooves using 3 mm or 6 mm diameter biopsy punches. The plugs were then sliced to obtain 1 mm thick cartilage disks containing the superficial zone as described previously [ 23 , 24 ]. Upon harvest, the disks were washed and equilibrated in PBS supplemented with PSA for up to 1 h. 3 mm explants were equilibrated individually in untreated control media comprised of DMEM supplemented with 1% HEPES buffer, 1% NEAA, 1% PSA, 0.4% L-proline, and 0.4% AA for 2 days at 37 °C and 5% CO 2 prior to any treatment.…”