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Item A blinded, placebo-controlled study on the clinical effects of vitamin E supplementation in dogs with osteoarthritis(Wiley Periodicals LLC. on behalf of the American College of Veterinary Internal Medicine., 2023-07-31) Gordon CL; Reeves SJ; Burchell RK; Thomson C; Gal A; Lopez-Villalobos N; Webster NSL; Litster KM; Mitchell RASBACKGROUND: Vitamin E has a positive effect in the management of osteoarthritis in humans, and in a previous study of dogs. It has been suggested to decrease C-reactive protein concentrations and liver enzyme activities in humans and animals. OBJECTIVE: To assess the effect of vitamin E supplementation on lameness, pain, pain medication requirement, clinical pathology variables, and quality of life in large-breed dogs with naturally occurring osteoarthritis. ANIMALS: Fifty-seven client-owned dogs with naturally occurring osteoarthritis. METHODS: Dogs received either vitamin E or placebo for 90 days in a randomized, placebo-controlled, double-blinded, prospective clinical trial. Clinical lameness scores, pain medication requirements, and owner questionnaires were used to assess response to treatment every 30 days. Blood samples were collected at enrollment and at the end of the study period. RESULTS: Vitamin E administration did not improve pain, lameness, or quality of life as assessed by owners and veterinarians. Vitamin E supplementation did not decrease the requirement for rescue pain relief. No changes in clinical pathology variables were observed after 90 days of vitamin E supplementation. Body weight was negatively associated with the lameness scores and requirement for rescue pain relief. CONCLUSION: Vitamin E supplementation did not have any observable positive effects in dogs with naturally occurring osteoarthritis.Item Infrared spectroscopy of serum fails to identify early biomarker changes in an equine model of traumatic osteoarthritis(Elsevier Ltd on behalf of Osteoarthritis Research Society International (OARSI), 2022-12) Panizzi L; Vignes M; Dittmer KE; Waterland MR; Rogers CW; Sano H; McIlwraith CW; Pemberton S; Owen M; Riley CBOBJECTIVE: to determine the accuracy of infrared (IR)-based serum biomarker profiling to differentiate horses with early inflammatory changes associated with a traumatically induced model of equine carpal osteoarthritis (OA) from controls. METHOD: unilateral carpal OA was induced in 9 of 17 healthy Thoroughbred fillies, while the remainder served as sham operated controls. Serum samples were obtained before induction of OA (Day 0) and weekly thereafter until Day 63 from both groups. Films of dried serum were created, and IR absorbance spectra acquired. Following pre-processing, partial least squares discriminant analysis (PLSDA) and principal component analysis (PCA) were used to assess group and time differences and generate predictive models for wavenumber ranges 1300-1800 cm-1 and 2600-3700 cm-1. RESULTS: the overall correct classification rate when classifying samples by group (OA or Sham) was 52.7% (s.d. = 12.8%), while it was 94.0% (s.d. = 1.4%) by sampling Day. The correct classification results by group-sampling Day combinations with pre-intervention serum (Day 0) was 50.5% (s.d. = 21.7%). CONCLUSION: with the current approach IR spectroscopic analysis could not differentiate serum of horses with induced carpal OA from that of controls. The high classification rate obtained by Day of sampling may reflect the effect of exercise on the biomarker profile. A longer study period (advanced disease) or naturally occurring disease may provide further information on the suitability of this technique in horses.Item Green-lipped (greenshell™) mussel (Perna canaliculus) extract supplementation in treatment of osteoarthritis: a systematic review(Springer Nature Switzerland AG, 2021-08) Abshirini M; Coad J; Wolber FM; Von Hurst P; Miller MR; Tian HS; Kruger MCOBJECTIVES: Intervention studies using New Zealand green-lipped or greenshell™ mussel (GSM) (Perna canaliculus) extract in osteoarthritis (OA) patients have shown effective pain relief. This systematic review summarises the efficacy of GSM extracts in the treatment of OA. METHODS: A literature search of the three databases EMBASE, MEDLINE, and Scopus was performed to identify relevant articles published up to March 2020. Inclusion criteria were clinical trials published in English measuring the effect of supplementation of whole or a lipid extract from GSM on pain and mobility outcomes in OA patients. RESULTS: A total of nine clinical trials were included in systematic review, from which five studies were considered appropriate for inclusion in a forest plot. Pooled results showed that GSM extracts (lipid extract or whole powder) provide moderate and clinically significant treatment effects on a visual analogue scale (VAS) pain score (effect size: - 0.46; 95% CI - 0.82 to - 0.10; p = 0.01). The whole GSM extract improved gastrointestinal symptoms in OA patients taking anti-inflammatory medications. The GSM extract was considered to be generally well tolerated in most of the studies. CONCLUSION: The overall analysis showed that GSM provided moderate and clinically meaningful treatment effects on OA pain. However, the current evidence is limited by the number and quality of studies, and further larger and high-quality studies are needed to confirm the effectiveness and to identify the optimal GSM format. Nevertheless, it is worth considering using GSM extracts especially for patients seeking alternative pain relief treatments with fewer side effects compared to conventional treatment.Item Effect of GreenshellTM mussel on osteoarthritis biomarkers and inflammation in healthy postmenopausal women: a study protocol for a randomized double-blind placebo-controlled trial(BioMed Central Ltd, 2021-12) Abshirini M; Coad J; Wolber FM; von Hurst P; Miller MR; Tian HS; Kruger MCBACKGROUND: New Zealand Greenshell™ mussels (GSM; Perna canaliculus) have recently been shown to decrease cartilage degradation in a rat model of induced metabolic osteoarthritis (MetOA). However, this effect has not been investigated in human subjects. This study aims to determine the effect of GSM powder on biomarkers of cartilage metabolism, bone resorption, and inflammation in New Zealand healthy overweight/obese postmenopausal women who are at early stage or at high risk of OA. METHOD: Fifty overweight or obese (BMI 25-35 kg/m2) postmenopausal women (aged 55-75 years) will be recruited by advertisement. Participants will be randomized based on a double-blind randomization schedule and stratified randomization based on BMI and age distribution. The participant will be assigned with a 1:1 allocation ratio to receive 3 g/d whole meat GSM powder or placebo (sunflower seed protein) for 12 weeks. Data on socio-demographics, physical activity, and dietary intake will be collected for each subject. Cartilage turnover biomarkers [(C-telopeptide of type II collagen (CTX-II), C-propeptide of type II procollagen (CPII), Cartilage oligomeric matrix protein (COMP)], and bone resorption marker (CTX-I) will be measured in blood and urine samples. Inflammatory status (hs-CRP and cytokine panel) will be assessed and iron status will be measured. Body composition including fat mass (FM), lean mass (LM), and fat percentage will be measured using dual-energy X-ray absorptiometry (DXA). Joint pain and knee function will be assessed using a 100-mm visual analog scale (VAS) and the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire, respectively. DISCUSSION: This trial will be the first to explore the effects of whole meat GSM powder on cartilage turnover, bone resorption, and inflammation biomarkers in overweight/obese postmenopausal women. The results from this trial will provide evidence on the efficacy of GSM in the prevention of OA. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12620000413921p . Registration on 27 March 2020.Item Non-polar lipid from greenshell mussel (Perna canaliculus) inhibits osteoclast differentiation(Elsevier Inc, 2021-12) Siriarchavatana P; Kruger MC; Miller MR; Tian HS; Wolber FMThe osteoclast-dependent bone resorption process is a crucial part of the bone regulatory system. The excessive function of osteoclasts can cause diseases of bone, joint, and other tissues such as osteoporosis and osteoarthritis. Greenshell mussel oil (GSM), a good source of long chain omega-3 polyunsaturated fatty acids (LCn-3PUFAs), was fractionated into total lipid, polar lipid, and non-polar lipid components and their anti-osteoclastogenic activity tested in RAW 264.7 cell cultures. Osteoclast differentiation process was achieved after 5 days of incubation with RANKL in 24-well culture plates. Introducing the non-polar lipid fraction into the culture caused a lack of cell differentiation, and a reduction in tartrate-resistant acid phosphatase (TRAP) activity and TRAP cell numbers in a dose-dependent manner (50% reduction at the concentration of 20 μg/mL, p < 0.001). Moreover, actin ring formation was significantly diminished by non-polar lipids at 10-20 μg/mL. The bone digestive enzymes released by osteoclasts into the pit formation were also compromised by downregulating gene expression of cathepsin K, carbonic anhydrase II (CA II), matrix metalloproteinase 9 (MMP-9), and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1). This study revealed that the non-polar lipid fraction of GSM oil contains bioactive substances which possess potent anti-osteoclastogenic activity.Item Effect of New Zealand Greenshell™ mussel on osteoarthritis biomarkers and inflammation in healthy postmenopausal women : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Nutritional Science, School of Health Sciences, Massey University, Palmerston North, New Zealand(Massey University, 2023) Abshirini, MaryamNew Zealand GreenshellTM Mussel (GSM) showed chondroprotective effects in a pre-clinical study using a rat model of metabolic osteoarthritis, warranting further assessment in a human study. This PhD project aimed to assess the effect of GSM supplementation on cartilage degradation biomarkers in humans, and to develop novel biomarkers through a metabolomic approach. A double-blind, placebo-controlled, longitudinal clinical trial was carried out in overweight postmenopausal women who were given 3 g/day whole meat GSM powder or placebo (sunflower seed protein) for 12 weeks. Plasma samples from the pre-clinical rat trial were assessed through an untargeted metabolomic approach, followed by metabolomic analysis of plasma samples from the clinical trial. In participants with active knee pain, the cartilage turnover biomarker C-terminal telopeptide of type II collagen was significantly lower in GSM participants compared to placebo at weeks 6 and 12. GSM significantly reduced joint pain and improved knee-related symptoms. GSM but not placebo altered the faecal microbiota population and reduced the rate at which body fat accumulation increased. However, no changes in inflammatory cytokines were found. The metabolomic analysis of rat plasma samples revealed that GSM supplementation regulated the alteration in plasma triglyceride and other lipids caused by a high-fat diet. In the plasma of human participants, GSM supplementation increased long-chain polyunsaturated fatty acids (PUFA), ceramide, and some other lipids. In both rats and humans, GSM suppressed the sphingomyelin synthesis pathway. Polar metabolites including threonine, histidine and pipecolic acid were significantly impacted in both rat and human and are potential metabolic biomarkers for the impact of GSM powder supplementation in metabolic osteoarthritis. In conclusion, consumption of GMS powder may provide cartilage protection and reduce joint pain, particularly in women with symptomatic knees. However, no significant impact was observed on circulating inflammatory cytokines, suggesting that GSM may exert anti-inflammatory effects at the microenvironmental rather than systemic level. The bioactive compounds present in GSM powder such as omega-3 PUFA and chondroprotective glycosaminoglycans may be responsible for the beneficial effect through inhibiting the breakdown of type II collagen in cartilage, regulating gut microbe abundance, improving body composition, and the metabolite profile which needs to be investigated in future research.Item Effects of whole greenshell mussel (Perna canaliculus) powder on macrophage, osteoblast, and chondrocyte cell models of metabolic osteoarthritis : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Health Sciences at Massey University, Palmerston North, New Zealand(Massey University, 2021) Rizwan, SaimaOsteoarthritis (OA) is a chronic, painful disorder of synovial joints in the hands, knees, hips, and spine. It is characterized by articular cartilage degeneration, subchondral bone sclerosis, and synovium inflammation. Obesity is an important risk factor, by exerting additional mechanical loading on the joints and by increasing the hormone leptin (LEP). LEP, an adipokine produced by white adipose tissue, is important in regulating the metabolic activities of inflammatory, cartilage and bone cells in OA pathogenesis. OA has no cure and is conventionally managed with painkilling medications. Oil from New Zealand GreenshellTM mussel (GSM) is also used to treat OA, but its mechanism of action is unclear, and it is not known whether peptides and other components in whole GSM may have additional health benefits in OA. This study investigated the effects of whole GSM using novel in vitro models of OA. LEP-stimulated J774A.1 macrophages, MC3T3-E1 pre-osteoblasts and differentiated osteoblasts, and ATDC5 pre-chondrocytes and differentiated chondrocytes modelled the behaviour of synovial macrophages, subchondral bone, and cartilage cells during OA. Blue mussel (BM) and GSM extracts were used to optimise macrophage assay conditions. Two whole GSM extracts were further tested in the in vitro models at non-cytotoxic concentrations. RT-qPCR was used to quantify biomarkers; chemical and staining assays were used to assess alkaline phosphatase activity and mineralization, proteoglycan, and collagen synthesis. LEP-induced inflammatory cytokine expression in macrophages peaked at 4 and was dose-dependent; neither mussel type ameliorated inflammation but BM alone significantly induced IL-1β, IL-6, TNF-α and IL-10 expression. GSM significantly increased osteoblast proliferation, mineral deposition, and expression of osteogenic markers Alp, Osx, Col10α1 and Runx2. In chondrocytes, GSM significantly blocked LEP-induced hypertrophic differentiation by suppressing alkaline phosphatase, Col10α1 and mineralized nodules and increasing Sox9 expression. This project developed simple but effective in vitro models of inflammatory, bone, and cartilage cells that mimic the physiological response to LEP and the pathological changes observed in OA and demonstrated that whole GSM may prevent OA by acting directly on bone and cartilage rather than acting through well recognized anti-inflammatory pathway, indicating novel protective effects of whole GSM on all three cell types.Item 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(Massey University, 2021) Siriarchavatana, ParkpoomOsteoarthritis (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.Item "I like to be treated like a person, a little smile never costs a thing" : weaving kaumātua experiences of living with osteoarthritis in Hawkes's Bay, Aotearoa New Zealand into a collaborative osteoarthritis-management toolkit : a thesis presented for the requirements for the degree of Doctor of Philosophy, Public Health, Massey University, Palmerston North, New Zealand(Massey University, 2018) Awatere, Sharon A.The global burden of osteoarthritis has major ramifications for societies and governments around the world. Despite a high rate of osteoarthritis, there is a low level of osteoarthritis-management knowledge and awareness in the Māori community. Numerous studies of Māori health have identified a need for new health communication approaches to osteoarthritis-management, in order to close the disconnection between Māori and non-Māori disease rates. Positive health management is the topic of the present thesis, as viewed through Māori eyes. It has been informed by the memories and aspirations of kaumātua who have lived through the challenges of living with osteoarthritis, but have emerged with qualities that enable them to enjoy older-age and to contribute to their own whānau, the Māori world, and wider society. These factors have been brought together into a Māori-centred toolkit, appropriate to modern health promotion, as they apply to Māori health perspectives of kaumātua in Hawke’s Bay. The present research was undertaken within the interpretivist paradigm using qualitative methods and Māori principles, aligned to a tīkanga (cultural principles) base. It is argued that Western science and a Māori-centered approach are relevant to research concerning osteoarthritis-management in the contemporary context, and reflect the realities of kaumātua with osteoarthritis, who live in both the Māori world, and wider society. The study drew upon the experiences, attitudes and beliefs of 20 kaumātua with osteoarthritis, employing interviews and group hui, to inform constructing an osteoarthritis-management toolkit, process and outcome appraisal. The research found that osteoarthritis-management for kaumātua, can be characterised by a two dimensional concept that incorporates a process dimension and an interpretive appraisal dimension. The process dimension is consistent with a values perspective. The appraisal dimension can be described in terms of complementary Māori specific outcome indicators of osteoarthritis-management. The outcome indicators are encapsulated by the idea that kaumātua, family and whānau know what issues deserve their attention and what is needed to address local problems. The Māori-specific outcome indicators for optimal osteoarthritis-management identified in the present study are: ‘Manākitanga’ (kind support); ‘Tino rangatiratanga’ (self-determination, and; ‘Oritetanga’ (equity and assessment). The overarching indicator is ‘Manākitanga-ā-tinana’ (culturally relevant approach to osteoarthritis management and relationship-based care).