The preventive effect of greenshell mussel meat against osteoarthritis in vivo : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Health Science At Massey University, Palmerston North, New Zealand

Abstract

Osteoarthritis (OA) is identified by progressive cartilage erosion of synovial joints. One of the most prevalent OA phenotypes, metabolic OA (MetOA), is linked to metabolic syndrome (MetS). MetS is a combination of obesity, type II diabetes, hypertension, and hyperlipidemia; the effects of these disorders can lead to the development of MetOA. Osteoporosis is characterised by loss of bone mineral density and is causally linked with a decrease in systemic estrogen levels. As MetS, OA and osteoporosis are all prevalent in postmenopausal women, it is possible they may be causally linked. For example, systemic low-grade inflammation in MetS may trigger inflammation in both joints and bone, which could be further aggravated by high fat/high sugar diet (HFHS)-induced obesity and gut dysbiosis. We hypothesized that chronic inflammation would be correlated with MetOA development and therefore decreasing inflammation would be protective. New Zealand greenshell mussel (GSM) contains anti-inflammatory properties shown to reduce OA symptoms and omega-3 fatty acids shown to reduce the development of post-menopausal osteoporosis. We hypothesized GSM could protect against both MetOA and osteoporosis reducing bone resorption, inhibiting inflammation and/or modulating beneficial gut microbes. In vitro, non-polar GSM lipids demonstrated bone-protective properties and significantly reduced osteoclast differentiation, tartrate-resistant acid phosphatase activity, actin ring formation and gene expression of matrix metalloproteinase, cathepsin K, carbonic anhydrase and nuclear factor of activating T cells 1. In vivo, aging, HFHS and OVX produced a rat model mimicking human MetS. Dietary whole GSM powder provided protection by significantly reducing a biomarker of collagen degradation and subsequent joint damage, as well as improving short-term bone mineral density and lean mass accrual. GSM-induced changes in gut microbiota were not correlated with dysbiosis. No changes in inflammatory markers were found, disproving our initial hypothesis and suggesting that chronic inflammation may not be a critical factor in MetOA. In conclusion, GSM as a dietary intervention may reduce the incidence or progression of MetOA but not via altering systemic inflammation or gut dysbiosis.