This is the first in a series of articles we will be publishing on the topics related to osteoarthritis, inflammation, precision nutrition and how targeting inflammation can help osteoarthritis patients manage their condition.
All views are our own and although signed off by our in-house doctor and always built in on verified research studies, please do remember to always consult a healthcare professional before making any decisions as to your own course of treatment. We are all unique.

Osteoarthritis (OA) remains a prevalent disease that afflicts more than 500 million individuals worldwide. The prevalence of OA is expected to rise due to various factors, including population growth and ageing with increased life expectancy, a higher prevalence of overweight and obesity, and the absence of drugs that can modify the progression of the disease. OA occurs most frequently in the hip, knee, and joints of the hand, foot, and spine (9).
Historically, OA was seen as a disease of the articular cartilage alone, but current understanding demonstrates that it involves the entire joint (5)(6). OA predominantly develops from the progressive wear and tear and consistent degradation of articular cartilage. Alterations in the synovium, joint ligaments, and the subchondral bone also play significant roles (7).
Interestingly, and offering hope for better treatment and management approaches, recent research shows that OA involves both inflammatory and metabolic mechanisms (7)(8). There is currently no known cure for OA and its progression differs among individuals, often in an unexplained way. Often, someone with significant XRay changes in the joint will report lower levels of pain than a person with barely any changes visible on a standard XRay scan.
The latest research from Duke University (1) and others into biomarkers, inflammation and lifestyle factors was able to predict the progression of osteoarthritis patients with above 70% accuracy, offering exciting possibilities for more effective treatment as we begin to understand the condition in more detail.
Understanding Articular Cartilage and Arthritis
What's Articular Cartilage?
Articular cartilage is like a protective layer on the ends of bones where they meet to form joints. It lets our joints move smoothly and cushions the stress when we're active.
This isn't just a plain layer, though. Inside, there's a web-like structure made of collagen and something called proteoglycans. Collagen gives strength to the cartilage, while proteoglycans soak up water and help resist pressure. Living within this web are cells called chondrocytes, which act like caretakers, ensuring the cartilage stays in good shape (11).
How Does Cartilage Work?
Under regular conditions, chondrocytes aren't super active. They're snugly packed in that web, which means they don't get a lot of nutrients. Their main job? Keeping the cartilage healthy, particularly by looking after the water-loving proteoglycans (13, 14).
But with age or conditions like osteoarthritis (OA), this changes.
What Happens with cartilage in Osteoarthritis?
Early on in OA, even if the cartilage looks fine, there are changes happening below the surface (15). Chondrocytes try to fix this damage. They produce more parts of the cartilage but also release proteins that can cause inflammation, like interleukin 1β, interleukin 6, and several others (16, 17).
These cells have something like sensors (called toll-like receptors) that detect when the cartilage is getting damaged (19). Once activated, these sensors might increase inflammation. They also pick up on other elements, such as certain crystals and substances that gather in our bodies as we get older or in conditions like diabetes (20-22).
As we move forward, some chondrocytes start behaving differently, becoming more inflammatory and less repair-focused. This change can be caused by external stresses and affects the tissue's balance (23).
In later stages of OA, these cells grow too much and eventually start dying off (24). As they die and the web-like structure breaks down, the cartilage suffers. This leads to bones rubbing against each other, causing pain and making movement tough.
Cartilage and Osteoarthritis - Summary
Articular cartilage acts as a protective cushion in our joints. But as we age or if we have conditions like OA, it can wear down, leading to painful joints. Understanding this can help in finding ways to better treat or prevent OA in the future.
Understanding the Synovium and Arthritis
What is Synovium?
Think of the synovium as a thin lining inside our joints, surrounding the fluid there (31). This lining has two layers and acts like a gatekeeper, deciding which molecules can enter or leave the joint space (32). One of its main jobs is to produce a special fluid that helps lubricate our joint surfaces, ensuring smooth movement. This fluid also provides essential nutrients to parts of the joint that don't have their own blood supply and helps in getting rid of waste products (33).
What Happens When Things Go Wrong?
In the early stages of osteoarthritis (OA), this lining can become inflamed, a condition called synovitis. When this happens, the lining might thicken, become more blood vessel-rich, and accumulate clusters of immune cells like T-lymphocytes and B-lymphocytes (34). This inflammation might be triggered by proteins that promote inflammation and by signals coming from damaged joint tissues (34). Once started, it's like a snowball effect. The inflammation in the synovium can further amplify inflammation in other parts of the joint.
In people with OA, researchers have found increased levels of certain inflammatory proteins in the synovial fluid and tissues. One protein that stands out is interleukin-15 (IL-15). This protein has a special role in attracting and activating immune cells. High levels of IL-15 in people with OA, compared to those without, hint that it might be a key player in driving the disease's progression (35).
Synovium and Osteoarthritis - Summary
The synovium is like a protective lining in our joints, making sure everything runs smoothly. But, in conditions like OA, it can become inflamed and contribute to worsening joint problems. Discovering how proteins like IL-15 play a role in this process can pave the way for better treatments.
Osteoarthritis and inflammation - conclusion
Osteoarthritis (OA) is often viewed as a wear-and-tear disease, affecting the protective cartilage inside our joints. However, it's becoming clearer that inflammation plays a pivotal role in its onset and progression.
Inside our joints, there's a layer called articular cartilage that ensures smooth movement. This cartilage contains a web-like structure made of collagen and proteoglycans, with cells called chondrocytes acting as caretakers. As people age or due to injuries, this cartilage can undergo changes. Even if it looks okay on the surface, beneath, the structure may start deteriorating. Chondrocytes respond by trying to repair the damage. But in doing so, they release proteins that promote inflammation, like interleukin 1β and interleukin 6.
Adding to this, chondrocytes have sensors called toll-like receptors that detect damage and can amplify the inflammatory response. These receptors also respond to certain elements that gather in the body with age or conditions like diabetes.
Another important player is the synovium, a lining inside our joints. When OA begins, the synovium can get inflamed, a condition called synovitis. This inflammation can be triggered by proteins and signals from damaged joint tissues, resulting in a snowball effect: inflammation in the synovium further stirs up inflammation in the cartilage.
A notable discovery is the protein interleukin-15 (IL-15), found in higher levels in OA patients. IL-15 is involved in attracting and activating immune cells, hinting at its role in driving OA's progression.
In essence, while wear and tear contribute to OA, it's the persistent cycle of inflammation—within the cartilage and synovium—that accelerates the disease, leading to pain and joint difficulties. Understanding this link is crucial for developing effective treatments for OA.
REFERENCES
1. Kaile Zhou et al. ,A “best-in-class” systemic biomarker predictor of clinically relevant knee osteoarthritis structural and pain progression.Sci. Adv.9, (2023).DOI:10.1126/sciadv.abq5095
5. Dieppe P. Developments in osteoarthritis. Rheumatology. 2011 Jan 17;50(2):245–7.
6. Abramson SB, Attur M. Developments in the scientific understanding of osteoarthritis. Arthritis Research & Therapy. 2009;11(3):227.
7. Mobasheri A, Batt M. An update on the pathophysiology of osteoarthritis. Annals of Physical and Rehabilitation Medicine. 2016 Dec;59(5-6):333–9.
8. Musumeci G, Aiello F, Szychlinska M, Di Rosa M, Castrogiovanni P, Mobasheri A. Osteoarthritis in the XXIst Century: Risk Factors and Behaviours that Influence Disease Onset and Progression. International Journal of Molecular Sciences [Internet]. 2015 Mar 16;16(12):6093–112. Available from: https://www.mdpi.com/1422-0067/16/3/6093/htm
9. Woolf AD, Pfleger B. Burden of major musculoskeletal conditions. Bulletin of the World Health Organization [Internet]. 2003;81(9):646–56. Available from: https://pubmed.ncbi.nlm.nih.gov/14710506/
11. Goldring MB, Marcu KB. Cartilage homeostasis in health and rheumatic diseases. Arthritis Research & Therapy. 2009;11(3):224.
12. Prydz K. Determinants of Glycosaminoglycan (GAG) Structure. Biomolecules. 2015 Aug 21;5(3):2003–22.
13. Archer CW, Francis-West P. The chondrocyte. The International Journal of Biochemistry & Cell Biology [Internet]. 2003 Apr 1;35(4):401–4. Available from: https://www.sciencedirect.com/science/article/pii/S1357272502003011
14. Martel-Pelletier J, Barr AJ, Cicuttini FM, Conaghan PG, Cooper C, Goldring MB, et al. Osteoarthritis. Nature Reviews Disease Primers [Internet]. 2016 Oct 13;2(1). Available from: https://www.nature.com/articles/nrdp201672
15. Goldring MB, Goldring SR. Articular cartilage and subchondral bone in the pathogenesis of osteoarthritis. Annals of the New York Academy of Sciences. 2010 Apr;1192(1):230–7.
16. Lohmander S, Tore Saxne, Heinegård D. Release of cartilage oligomeric matrix protein (COMP) into joint fluid after knee injury and in osteoarthritis. Annals of the Rheumatic Diseases. 1994 Jan 1;53(1):8–13.
17. Wojdasiewicz P, Poniatowski ŁA, Szukiewicz D. The Role of Inflammatory and Anti-Inflammatory Cytokines in the Pathogenesis of Osteoarthritis. Mediators of Inflammation. 2014;2014:1–19.
18. Troeberg L, Nagase H. Proteases involved in cartilage matrix degradation in osteoarthritis. Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics [Internet]. 2012 Jan;1824(1):133–45. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3219800/
19. Kim HA, Cho ML, Choi HY, Yoon CS, Jhun JY, Oh HJ, et al. The catabolic pathway mediated by Toll-like receptors in human osteoarthritic chondrocytes. Arthritis & Rheumatism. 2006;54(7):2152–63.
20. Miller RE, Scanzello CR, Malfait AM. An emerging role for Toll-like receptors at the neuroimmune interface in osteoarthritis. Seminars in Immunopathology [Internet]. 2019 Sep [cited 2023 Apr 6];41(5):583–94. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858588/
21. Sokolove J, Lepus CM. Role of inflammation in the pathogenesis of osteoarthritis: latest findings and interpretations. Therapeutic Advances in Musculoskeletal Disease. 2013 Jan 23;5(2):77–94.
22. Loeser RF, Yammani RR, Carlson CS, Chen H, Cole A, Im HJ, et al. Articular chondrocytes express the receptor for advanced glycation end products: Potential role in osteoarthritis. Arthritis & Rheumatism. 2005;52(8):2376–85.
23. Loeser RF. Aging and osteoarthritis: the role of chondrocyte senescence and aging changes in the cartilage matrix. Osteoarthritis and Cartilage [Internet]. 2009 Aug;17(8):971–9. Available from: https://www.oarsijournal.com/article/S1063-4584(09)00062-4/pdf
24. Sandell LJ. Etiology of osteoarthritis: genetics and synovial joint development. Nature Reviews Rheumatology. 2012 Jan 10;8(2):77–89.
25. Hwang H, Kim H. Chondrocyte Apoptosis in the Pathogenesis of Osteoarthritis. International Journal of Molecular Sciences. 2015 Oct 30;16(11):26035–54.
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31. Smith MD, Wechalekar MD. 4 - The synovium [Internet]. Hochberg MC, Silman AJ, Smolen JS, Weinblatt ME, Weisman MH, editors. ScienceDirect. Philadelphia: Mosby; 2015 [cited 2023 Sep 21]. p. 27–32. Available from: https://www.sciencedirect.com/science/article/abs/pii/B9780323091381000048?via%3Dihub
32. D. Smith M. The Normal Synovium. The Open Rheumatology Journal [Internet]. 2011 Dec 30;5(1):100–6. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3263506/
33. Brannan SR, Jerrard DA. Synovial fluid analysis. The Journal of Emergency Medicine. 2006 Apr;30(3):331–9.
34. Scanzello CR, Goldring SR. The role of synovitis in osteoarthritis pathogenesis. Bone. 2012 Aug;51(2):249–57.
35. Scanzello CR, Umoh E, Pessler F, Diaz-Torne C, Miles T, DiCarlo E, et al. Local cytokine profiles in knee osteoarthritis: elevated synovial fluid interleukin-15 differentiates early from end-stage disease. Osteoarthritis and Cartilage. 2009 Aug;17(8):1040–8.
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