gms | German Medical Science

Objectives: Meanwhile a link between OA and type 2 diabetes mellitus (T2DM) has been strongly suggested. However, the shared pathogenetic mechanisms remain unclear. The aims of this study were (1) to assess whether early onset OA features are detectable in Zucker Diabetes Fatty (ZDF) rats which clinically develop T2DM (fa/fa) or not (fa/+) when fed a high protein diet and (2) to define the specific response of chondrocytes from diabetic versus non-diabetic ZDF rats to inflammatory stimuli in vitro.

Methods: Blood glucose levels of ZDF rats (fa/fa and fa/+, both receiving high protein diet) were measured. Typical features of T2DM were assessed by histopathological investigation of pancreas, liver, spleen, kidneys and heart using self-designed scoring systems (Hematoxylin Eosin, HE and Sirius red stain). In addition, histopathology (HE and alcian blue staining) of the whole knee joints of 22 diabetic and non-diabetic ZDF rats was assessed using diverse scoring systems for articular cartilage or meniscus degeneration and synovitis/Hoffa fat pad inflammation.

Isolated chondrocytes from diabetic and non-diabetic ZDF rats were exposed to TNF α (10 ng/mL, 24-72 h). Cell metabolism, proliferation, gene and protein expression of type II and I collagens were assessed (proliferation, metabolic assays, Real time PCR (q-PCR) and immunolabeling).

Results and Conclusion: In contrast to heterozygous fa/+ animals continuously elevated blood glucose level confirmed T2DM in homozygous ZDF rats (fa/fa). T2DM was associated with clinical features and typical pancreas, liver, spleen, kidney and heart degeneration. Faint degenerative changes in joint cartilage and menisci as well as synovitis could be observed in the joints of T2DM but also in those of some non-diabetic animals. TNF α inhibited significantly chondrocytes proliferation at 24 h in chondrocytes derived from T2DM rats and at 72 h in both, T2DM and non-diabetic rat-derived chondrocytes (not significant). The suppression of the metabolic activity in chondrocytes derived from diabetic rats and/or exposed to TNF α did not reach the significance level. Gene expression of types II and I collagen was significantly impaired in chondrocytes derived from non-diabetic rats exposed to TNF α and in chondrocytes from individuals suffering from T2DM, irrespectively of whether being treated with TNF α or not. TNF αdid not significantly affect type II collagen but significantly reduced type I collagen protein expression in chondrocytes from non-diabetic individuals. The ZDF rat is a valuable model of T2DM displaying its major consequences. Despite of only faint changes of cartilage degradation and synovitis detectable in situ in the knee joints of T2DM rats, proliferation and extracellular matrix gene expression of chondrocytes deriving from T2DM rats is severely impaired.