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Fat and Osteoarthritis Tricia Ferguson & Parul Srivastav.

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Presentation on theme: "Fat and Osteoarthritis Tricia Ferguson & Parul Srivastav."— Presentation transcript:

1 Fat and Osteoarthritis Tricia Ferguson & Parul Srivastav

2 Castañeda S, Roman-Blas J, Largo R, Herrero-Beaumont G. Osteoarthritis: a progressive disease with changing phenotypes. Rheumatology. 2014; 53: 1-3. doi: /rheumatology/ket247 Herrero-Beaumont G, Roman-Blas J, Castañeda S, Jimenez S. Primary osteoarthritis no longer primary: three subsets with distinct etiological, clinical, and therapeutic characteristics. Seminars in Arthritis and Rheumatism. [Online] 2009; 39: Available from: [Accessed 27th January 2014]. “OA is a heterogeneous syndrome” “Metabolic OA” another OA phenotype?

3 “White adipose tissue is not inert but metabolically active; it secretes a wide variety of adipokines.” LEPTIN ADIPONECTIN CHEMERIN LIPOCALIN 2 VASPIN APELIN OMENTIN RESISTIN VISFATIN

4 Fat aka Adipose tissue Adipokines Cytokines released from fat tissue – chemicals released from cells which are involved in inflammation Inflammation Damage

5 Studies which have linked metabolic syndrome to OA Zhuo Q, Yang W, Chen J, Wang Y. Metabolic syndrome meets osteoarthritis. Nature Reviews Rheumatology. [Online] 2012; 8: Available from: [Accessed 29th January 2014]. HTN → subchondral ischaemia → compromised nutrient exchange into articular cartilage → triggers bone remodelling → OA dyslipidaemia + deregulated cellular lipid metabolism in joint tissues → ectopic lipid deposition in chondrocytes → OA hyperglycaemia → local effects of oxidative stress and advanced glycation end-products → cartilage damage → OA hyperglycaemia → glucose accumulation → low-grade systemic inflammation → OA obesity-related metabolic factors (e.g. altered levels of adipokines) → induce expression of proinflammatory factors + degradative enzymes → inhibition of cartilage matrix synthesis → stimulation of subchondral bone remodelling → OA

6 Prevalence of Obesity TotalOverweight/ Obese Other Rheum Conditions OAOther Co- morbidities SexAge 2822RA, SLE, myositis, vasculitis, mechanical back pain, fibromyalgia, Sjogrens, other connective tissue diseases 11 (7- knees ) (4 - hands) All overweight High BP, T2DM, H.Pylori, Gynae complaints, F (17) M(5) 31-40: : : : : 5 Sample – Rheumatology Clinic – 27/01/14

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9 Mrs ABC – year old lady Appointment for knee injection OA – both knees Obese Complaining of – pain, reduced ability to carry out daily activities, strain on family Trying to lose weight – personal trainer junk food

10 Obesity and OA Linked long time ago: 1988 – data from US National Health Survey Obese women  risk of OA X 4 Obese men  risk of OA X 5 Widely accepted theory of mechanical stress – can cause direct joint damage especially in weight bearing joints – knees Inhibition of cartilage matrix synthesis Pro-inflammatory factors: COX2, NO, PGE 2, IL-1β However – increased BMI associated with increased of OA in hands (Carman et al: prospective study with 23 year follow-up; n=1267)

11 Leptin 16 kDa non-glycosylated peptide hormone LEP gene and ob gene (mice) Class 1 cytokine family Directly correlated with WAT mass

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13 Leptin Dummon et al (2003): leptin levels in synovial fluid and cartilage in OA patients

14 Leptin – role in OA Chondrocytes stimulated with leptin  increased proliferation + synthesis of proteoglycans and collagen - Anabolic role in cartilage metabolism? Lots of contrary evidence for pro-inflammatory role: inflammatory markers (MMP-9, MMP-13, NO, PGE 2, IL-8) Higher level of leptin in OA patients knee injection in rats – proteolytic enzymes and growth factors Higher levels in females – even when adjusted for BMI

15 Effects of ↑ adiponectin ↑ NOS2 in chondrocytesNO inhibits collagen and proteoglycan synthesis, enhances apoptosis, and inhibits B1 integrin-dependent adhesion to the ECM ↑ IL-6 in chondrocytesInhibits chondrocyte proliferation and depresses proteoglycan synthesis, enhances proteoglycan synthesis in combination with IL-1β ↑ MMP-3 in chondrocytes ↑ MMP-9 in chondrocytes ↑ MCP-1 in chondrocytes ↑ VCAM-1 in chondrocytes? Induction of chemotactic molecules → monocyte and leukocyte recruitment → ? cartilage-degrading processes Collagen type-2 degradation → Type-2 collagen neoepitope ↑ IL-6 in synovial fibroblasts Jikko A, Wakisaka T, Iwamoto M, Hiranuma H, Kato Y, Maeda T et al. Effects of interleukin-6 on proliferation and proteoglycan metabolism in articular chondrocyte cultures. Cell Biology International. 1998; 22(9-10): Amin A, Abramson S. The role of nitric oxide in articular cartilage breakdown in osteoarthritis. Current opinion in rheumatology. 1998; 10(3):

16 Weight Loss and OA Numerous studies have shown benefits of weight loss (Framingham and ADAPT studies) But is it just a mechanical difference or do adipokines play a role as well? Toda et al (1998) – weight loss programme in OA patients – loss of fat more important than weight reduction in reducing symptoms Richette et al (2010) – 44 patients pre and post gastric surgery massive decrease in BMI (20%) Measurements : pain, function low-grade inflammation biomarkers of cartilage synthesis and degradation

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18 Primary Care (weight loss) Specialist Care (+ drugs/ painkillers, injections, physio) Extreme Interventions (TKR, bariatric surgery etc.) Summary Important to address the disease process at an earlier stage OA as reversible disease?? (MRI evidence of cartilage repair following weight loss) Management of clinical symptoms (chiefly pain) with reduction in either calories (Leeds) or fat % of body weight

19 Many thanks to: Dr Bernie Colaço Prof Anthony Leeds Laura Paul

20 References Castañeda, S., Roman-Blas, J. A., Largo, R. & Herrero-Beaumont, G. What is osteoarthritis today? A progressive disease of changing phenotypes. Rheumatology (Oxford) (2014) Knoop, Jesper, et al. "Identification of phenotypes with different clinical outcomes in knee osteoarthritis: data from the Osteoarthritis Initiative." Arthritis care & research (2011): Zhuo, Qi, et al. "Metabolic syndrome meets osteoarthritis." Nature Reviews Rheumatology 8.12 (2012): Pottie, P., et al. "Obesity and osteoarthritis: more complex than predicted!." Annals of the rheumatic diseases (2006): Lago, Francisca, et al. "Adipokines as emerging mediators of immune response and inflammation." Nature clinical practice Rheumatology 3.12 (2007): Presle, N., et al. "Differential distribution of adipokines between serum and synovial fluid in patients with osteoarthritis. Contribution of joint tissues to their articular production." Osteoarthritis and Cartilage 14.7 (2006): Hu, Peng-fei, Jia-peng Bao, and Li-dong Wu. "The emerging role of adipokines in osteoarthritis: a narrative review." Molecular biology reports 38.2 (2011): Dumond, Hélène, et al. "Evidence for a key role of leptin in osteoarthritis." Arthritis & Rheumatism (2003): Berry, Patricia A., et al. "Temporal relationship between serum adipokines, biomarkers of bone and cartilage turnover, and cartilage volume loss in a population with clinical knee osteoarthritis." Arthritis & Rheumatism 63.3 (2011): Aspden, Richard M. "Obesity punches above its weight in osteoarthritis." Nature Reviews Rheumatology 7.1 (2010):


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