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Although HMOs are predominantly known for their role in modulating the human gut microbiome, emerging research shows that they also exhibit anti-inflammatory properties, both within and outside of the colonic environment.
Inflammatory diseases come in all shapes and sizes, bringing with them an array of signs and symptoms. One such condition that arises from low-grade inflammatory processes is osteoarthritis.And for anyone who lives with the condition, you’ll know that this can be a debilitating and painful experience.
Current treatments include non-steroid anti-inflammatory drugs (NSAIDs), corticosteroid injections, and in the worst cases, surgery, but what if HMOs had the potential to protect against the development of osteoarthritis?
Well, a study published in 2017 looked at just that and in this article we’ll investigate what osteoarthritis is, who it affects, and uncover the key results.
Osteoarthritis is the most common form of arthritis which causes joints to become stiff and sore. Some people refer to it as a degenerative disease or simply put it down to wear and tear[i], but others concur that it is driven by low-grade inflammatory processes[ii].
Its development involves the breakdown of cartilage, a type of strong, connective tissue with a key function to protect the joints. Cartilage acts like a shock absorber, so if it begins to ‘wear out’ or break down, it can cause the ends of your bones to rub together, causing pain. However, osteoarthritis also causes a remodelling of underlying bone structures, ectopic bones, and inflammation in the synovial lining.
The breakdown of cartilage and the wearing of the underlying bone often happens over a period of time, getting worse the longer it occurs. In some people, it can be so severe that they are no longer able to carry out their usual daily tasks, including work.
Osteoarthritis can affect any joint in the body, but the most commonly affected areas are the:
The main symptoms of osteoarthritis are:
The severity of the symptoms will vary from person to person. It may be that symptoms are worse when you do more physical activity or can be affected by the weather. For some, the symptoms are a continuous feature of their everyday life.
Osteoarthritis can affect anyone but it’s more common in older people, for example women over 50. Other factors that can contribute to its development are:
Although there is currently no cure for osteoarthritis, there are treatments available to help relieve the symptoms. These are mainly supportive measures to help relieve pain or make everyday activities easier to carry out.
The main treatments for osteoarthritis are:
One of the key supportive measures to remember when living with osteoarthritis is exercise. Although you may be worried that physical activity will cause you pain, it can actually have the opposite effect because it:
Medicines are also an option for controlling the pain associated with osteoarthritis. Sometimes a combination of exercise, lifestyle changes, medication, and supportive measures are required.
The painkiller the doctor will prescribe you will be based on several factors, particularly the severity of your pain.
Some of the medications available for osteoarthritis, include:
As well as lifestyle changes and medicine, you may choose to experiment with supportive measures to help you carry out your daily tasks in a more comfortable way. These could include:
Research into human milk oligosaccharides (HMOs) has shown that they have a wide range of biological functions that can benefit bone growth as well as have anti-inflammatory effects. Both of which could be important in preventing the development of osteoarthritis.
Of particular interest is 3’-Sialyllactose. In this section, we’ll focus in on what 3’-Siallylactose is and what the research has revealed about its potential therapeutic use in osteoarthritis.
3’-Siallylactose is an abundant sialylated HMO found naturally in human breast milk, which basically means it is a sialic acid bound to a molecule of lactose. Some earlier research has highlighted that 3’-Sialyllactose alongside 6’-Sialyllactose could help to support our cognition as well as prevent the adhesion of pathogenic organisms[vi].
The structure of 3’-Sialyllactose consists of “the N-acetyl-D-neuraminic acid unit is connected to the galactose unit of lactose at the 3 position.”[vii] Although 3’-Sialyllactose has been shown to have anti-inflammatory properties and can effectively support the immune system, it’s function within degenerative diseases including osteoarthritis is still largely unknown.
At least, it was.
3’-Sialyllactose first gained attention in the 1980s when scientists at the University of Oxford found that the molecule, isolated from cows, could act on rheumatoid arthritis. Although a patent was acquired, the generation of a commercial sialyllactose product fell by the wayside and interest in the molecule largely diminished.
Until 2017, when Jeon et al. (2018) published their findings using a form of enzymatically synthesised 3’-Sialyllactose (3’-SL). The purpose of the study was to investigate the regulation of both anabolic and catabolic processes by 3’-Sialyllactose in the development of osteoarthritis.
The research showed that 3’-SL promoted the regeneration of cartilage and prevented its destruction often associated with the diseasevii. Scientists found that 3’-SL does this by stopping the expression of three enzymes called Mmp3, Mmp13 and Cox2, known to be upregulated by proinflammatory messengers or cytokines, especially IL-1β.
This is significant because osteoarthritis is an example of a cartilage degenerative disease whereby the extracellular matrix (ECM) is reduced because ECM protein synthesis stops and matrix degradation and inflammation occur. During the development of osteoarthritis, Col2a1, a gene responsible or making type 2 collagen in the cartilage, is depleted leading to a cascade of inflammatory processes.
However, the sialylated HMO, 3’-SL actually promotes the production of Col2a1, driving the formation of cartilage in osteoarthritic joints by inhibiting the expression of enzymes known to degrade cartilage induced by proinflammatory cytokines.
This research was backed up by a further study published in 2018 which investigated the effect of 3’SL on collagen-induced arthritis in mice. The results showed that 3’-SL reduced the severity of the disease in affected mice by reducing swelling, incidence rate and the level of inflammatory cytokines in the blood[viii]. The molecules also blocked the NF-Κb signalling pathway, known to trigger the expression of cartilage destruction genes responsible for osteoarthritis[ix].
A further study using rheumatoid arthritis minipig models, investigated the effects of 3’-SL on rheumatoid arthritis. Researchers injected 3’-SL into the left knee joint cavity once a week for four weeks and found that it had a therapeutic effect on collagen-induced arthritis[x].
The increasing research and clinical validation into the beneficial effects of this HMO, mean that 3’-SL is an exciting potential therapy for osteoarthritis.
Yes, you can!
Now you’re probably wondering, “where can I get my hands on some 3’-SL?”
Well, the simple answer is, right here.
Our SuperHMO® Prebiotic Mix contains five major types of HMO including 3’-Sialyllactose. This super mix helps to support your gut microbiome but also has numerous benefits throughout your body. That’s because it feeds many key species of gut bacteria, widening its positive impact.
Osteoarthritis is a degenerative condition that causes the breakdown of cartilage resulting in stiff and painful joints. The breakdown of cartilage is thought to be caused by proinflammatory cytokines and the loss of Col2a1, a main component of the cartilage extracellular matrix.
The disease can affect anyone and can cause debilitating symptoms. Although there is currently no cure, lifestyle changes and painkillers can help to manage the symptoms. However, a particular type of human milk oligosaccharide, 3’-SL, is showing promise for limiting osteoarthritis. Research shows that it can regenerate cartilage and prevent the inflammatory processes associated with the development of the disease.
Written by: Leanne Edermaniger, M.Sc. Leanne is a professional science writer who specializes in human health and enjoys writing about all things related to the gut microbiome.
[i] Osteoarthritis (OA) [Internet]. Centers for Disease Control and Prevention; 2020 [cited 2023 Jun 16]. Available from: https://www.cdc.gov/arthritis/basics/osteoarthritis.htm#:~:text=Osteoarthritis%20(OA)%20is%20the%20most,underlying%20bone%20begins%20to%20change.
[ii] Robinson WH, Lepus CM, Wang Q, Raghu H, Mao R, Lindstrom TM, Sokolove J. Low-grade inflammation as a key mediator of the pathogenesis of osteoarthritis. Nat Rev Rheumatol. 2016 Oct;12(10):580-92. doi: 10.1038/nrrheum.2016.136. Epub 2016 Aug 19. PMID: 27539668; PMCID: PMC5500215.
[iii] Overview - Osteoarthritis [Internet]. NHS; 2023 [cited 2023 Jun 16]. Available from: https://www.nhs.uk/conditions/osteoarthritis/
[iv] Treatment and support: Osteoarthritis [Internet]. NHS; 2023 [cited 2023 Jun 19]. Available from: https://www.nhs.uk/conditions/osteoarthritis/treatment/
[v] Osteoarthritis: Symptoms, diagnosis, and treatment: Arthritis foundation [Internet]. [cited 2023 Jun 19]. Available from: https://www.arthritis.org/diseases/osteoarthritis
[vi] Wang B. Molecular mechanism underlying sialic acid as an essential nutrient for brain development and cognition. Adv Nutr. 2012 May 1;3(3):465S-72S. doi: 10.3945/an.112.001875. PMID: 22585926; PMCID: PMC3649484.
[vii] Jeon J, Kang LJ, Lee KM, Cho C, Song EK, Kim W, Park TJ, Yang S. 3'-Sialyllactose protects against osteoarthritic development by facilitating cartilage homeostasis. J Cell Mol Med. 2018 Jan;22(1):57-66. doi: 10.1111/jcmm.13292. Epub 2017 Aug 7. PMID: 28782172; PMCID: PMC5742729.
[viii] Kang LJ, Kwon ES, Lee KM, Cho C, Lee JI, Ryu YB, Youm TH, Jeon J, Cho MR, Jeong SY, Lee SR, Kim W, Yang S. 3'-Sialyllactose as an inhibitor of p65 phosphorylation ameliorates the progression of experimental rheumatoid arthritis. Br J Pharmacol. 2018 Dec;175(23):4295-4309. doi: 10.1111/bph.14486. Epub 2018 Oct 17. PMID: 30152858; PMCID: PMC6240131.
[ix] Rigoglou S, Papavassiliou AG. The NF-κB signalling pathway in osteoarthritis. Int J Biochem Cell Biol. 2013 Nov;45(11):2580-4. doi: 10.1016/j.biocel.2013.08.018. Epub 2013 Sep 1. PMID: 24004831.
[x] Kim YJ, Lee JY, Yang MJ, Cho HJ, Kim MY, Kim L, Hwang JH. Therapeutic effect of intra-articular injected 3'-sialyllactose on a minipig model of rheumatoid arthritis induced by collagen. Lab Anim Res. 2022 Mar 22;38(1):8. doi: 10.1186/s42826-022-00119-2. PMID: 35314005; PMCID: PMC8939226.
