Abstract
Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage loss and reduced joint function. OA risk factors are age and obesity. Many adipokines are altered by obesity but also OA although systemic adipokine regulation in OA is not always clear. Therefore, metabolic effects of diet-induced obesity on OA development as well as the influence of obesity and OA progression on systemic vs. local adipokine expression in joints were compared. C57Bl/6-mice fed with HFD (high fat diet) or normal diet prior to destabilization of the medial meniscus (DMM) were sacrificed 4/6/8 weeks after surgery. Sera were evaluated for adiponectin, leptin, visfatin, cytokines. Liver grading and staging for non-alcoholic steatohepatitis (NASH) was performed and crown-like structures (CLS) in adipose tissue measured. OA progression was scored histologically. Adipokine-expressing cells and types were evaluated by immunohistochemistry. Time-dependent changes in DMM-progression were reflected by increased systemic adiponectin levels in DMM especially combined with HFD. While HFD increased serum leptin, DMM reduced systemic leptin significantly. OA scores correlated with bodyweight, leptin and hepatic scoring. Locally, increased numbers of adiponectin- and leptin-producing fibroblasts were observed in damaged menisci but visfatin was not changed. Local adipokine expression was independent from systemic levels, suggesting different mechanisms of action.
Highlights
Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage loss and reduced joint function
high fat diet (HFD) animals with destabilization of the medial meniscus (DMM) scored with 2.47 ± 0.88 (n = 5) compared to healthy HFD-fed animals (0.11 ± 0.09; n = 6, p < 0.0001) 4 weeks after induction. 6 weeks after surgery, the normal diet (ND) group showed an OA score of 3.06 ± 1.69 (n = 5) vs. ND healthy of 0.03 ± 0.07 (n = 6, p = 0.0001), whereas the HFD group had a higher score of 4 ± 1.19 (n = 6) compared to HFD healthy (0.11 ± 0.17; n = 6; p < 0.0001)
OA progression between 4 and 6 weeks was stronger than 6 to 8 weeks. 8 weeks after surgery the OA score in ND mice was 2.63 ± 1.65 (n = 8) compared to ND healthy controls 0.17 ± 0.13 (n = 7, p = 0.0002) and in HFD mice 4.67 ± 1.06 (n = 5) vs. HFD healthy animals 0.19 ± 0.26 (n = 8, p < 0.0001) (Fig. 1d)
Summary
Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage loss and reduced joint function. Time-dependent changes in DMM-progression were reflected by increased systemic adiponectin levels in DMM especially combined with HFD. (g) Representative H/E staining of the liver showing increased hepatic fat in HFD animals (upper panel) while hepatic fat was reduced in animals fed with HFD and DMM (lower panel) at early time points. (h) Mice fed with HFD showed increased glycogen accumulation in the liver (upper panel) which was reduced in animals fed with HFD and DMM (lower panel). Some studies showed that weight bearing joints such as knee and hip are frequently affected in obese patients, and non-weight-bearing joints such as fingers[2] Whether this is a consequence of altered adipokine levels is not fully e lucidated[2]
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