Differential Responses of Articular Chondrocytes from Diabetic and Non-Diabetic Rats to Glucose Conditions and Inflammatory Stimuli: Influence of a Vitamin K2 Enriched Diet.

Abstract

ObjectiveMeanwhile, the association between osteoarthritis (OA) and type 2 diabetes mellitus (T2DM) is well known. However, it remains unclear whether vitamin K2 (vit.K2) could exert chondroprotective effects. Hence, this study investigates the interrelation between OA and T2DM under the influence of vit.K2 in chondrocytes.MethodsUsing an in vitro OA/T2DM model, articular chondrocytes were harvested from adult male Zucker diabetic fatty (ZDF) Leptfa/Crl rats, categorized as non-diabetic (heterozygous: fa/+) or diabetic (homozygous: fa/fa). Based on vit.K2 supplementation of the rats, four groups arose: control without or with vit.K2 and diabetic without or with vit.K2 supplementation. Inflammatory conditions simulating OA were induced by exposing chondrocytes to tumor necrosis factor alpha (TNFα) and C5a. Chondrocyte response was analyzed using proliferation, metabolic and wound healing assays, immunolabeling, as well as gene expression analyses.ResultsThe proliferation of chondrocytes from control rats with vit.K2 supplementation was significantly higher than those without vit.K2 feeding, under both normoglycemic (NG) and hyperglycemic (HG) conditions. The wound closure ability of chondrocytes was significantly higher in the non-diabetic compared with the diabetic chondrocyte donor group. TNFα and C5a exerted catabolic effects under HG conditions by significantly inducing Tnfα gene activity in chondrocytes of control rats without vit.K2 supplementation and a significant reduction of collagen type 2 gene expression in those cells of control rats with vit.K2 supplementation.ConclusionsThe response of chondrocytes derived from non-diabetic and diabetic donors differed. The vit.K2 supply of chondrocyte donor rats exerted anabolic effects on chondrocytes.