The use of dietary restriction to reduce the progression of osteoarthritis (OA) in a spontaneous model of OA
Obesity is strongly associated with knee osteoarthritis (OA), and weight loss has been implicated in reducing the progression of the disease. The initiation and progression of OA cartilage lesions and osteophyte formation in the Dunkin Hartley (DH) guinea pig model of OA have been well characterised, and many features parallel findings in human OA tissue. However, the role of the bone, including subchondral and metaphysical bone in obesity-mediated OA progression has not been defined. Dietary restriction (DR) was used to reduce weight gain, and the effects on OA progression, bone metabolism, bone quality and gene expression were investigated in DH guinea pigs. Cartilage lesion formation was determined using macroscopic analysis. Changes in bone mass were characterised by measurement of the tibial plateau dimensions, pQCT and histomorphometry. These data were further confirmed by assessing the levels of urinary and serum biomarkers of bone turnover. Microarray technology was utilised to asses the effects of DR on the expression of genes involved in OA and/or bone function and regulation. Attempts were made to validate the expression of genes from these experiments by TaqMan(TM) PCR and immunodetection. Dietary restriction reduced bodyweight, cartilage lesion severity and bone turnover, but increased osteophyte formation. Microarray was performed but due to a number of issues, including validation, these data must be treated with caution. Overall, DR was found to prevent the progression of knee OA and OA-induced changes in bone metabolism, many features of which support findings from human OA studies.