High carbohydrate high fat diet induced metabolic overload cause osteoarthritis-like changes of the cartilage and shift macrophage polarization status in a rat model — ASN Events
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High carbohydrate high fat diet induced metabolic overload cause osteoarthritis-like changes of the cartilage and shift macrophage polarization status in a rat model (#208)

Antonia Sun 1 , Indira Prasadam 1 , Yin Xiao 1
  1. Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, QLD, Australia

Background: The association between osteoarthritis (OA) and obesity-induced metabolic syndrome has been suggested by many studies, however,the mechanisms underlying this link are unclear. Recently, a new subtype of OA, called metabolic OA, has been identified as disorder that is associated with metabolic overload-associated low-grade systemic inflammation. In this study, we aim to establish a causal relation between obesity associated metabolic syndrome and development of OA pathology. 

Methods: Male Wistar rats were fed with high-carbohydrate–high-fat (HCHF) or corn starch (CS) diet from 10 to 26 weeks of age. At sacrifice, knee joint Modified Mankin scores and synovial thickening scores were measured. Immunohistochemistry of CS and HCHF rat knee joint sections were performed to demonstrate specific expression of activated macrophages. In vitro, chondrocytes and conditioned medium of activated macrophage in co-culture were used to investigate whether polarized macrophage play role in the detrimental effect on cartilage. 

Results: Based on histological results, we identified that obesity associated metabolic syndrome in dietary rat models leads toa significant accumulation of inflammatory macrophages in the activated synovium of the knee joint.Increased CD68+ macrophage infiltration with a strong co-expression of the M1 macrophage marker in the synovim were also observed. Along with synovial inflammation, OA-like cartilage changes were also observed. In accordance with the in vivo findings, M1 polarized macrophages significantly inhibit SOX9 and ACAN and induce MMP-13 and RUNX2 gene expression.

Conclusion: These results indicated that obesity-induced metabolic syndromes affects the balance of M1/M2 macrophages and lead it skewing toward a pro-inflammatory state in synovium. M1 polarized macrophages elicit the unfavorable effect  of chondrocytes by directly impacting chondrogenic expression. Our study provides a new overvies of the role of synovial macrophages in promoting destructive responses in metabolic OA and might therefore be used as a therapeutic strategy for the development of disease-modifying anti-OA drugs (DMOADs).