GLYCOSTAR GLYcomic OSTeoARthrithis Research
Project manager
Professor Niclas Karlsson
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Contact info
Other researchers
Colin Charnock
Milada Småstuen
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Osteoarthrithis (OA) is an endemic musculoskeletal disease influencing as much as 13% of Norwegians between the ages of 24-74 years, translating to approximately 450,000 individuals. There is a current lack of OA health care options for these patients. For example, at present there are no disease-modifying OA drugs, DMOAD and biomolecular diagnostics and prognostics are lacking. Current treatment of OA is limited to management of OA-related pain, physiotherapy and ultimately replacement surgery. Most OA are idiopathic, even though risk factors have been identified such as joint trauma, age and obesity. There is a complex and to many extend an unexplored aetiology of OA, where several biomolecular endotypes and phenotypes are merged under the common OA umbrella.
Glycomics is one of the later omic techniques studying the complex carbohydrates that are present on biosurfaces. On all cell surface there is a layer of glycolipids and glycoproteins that makes up how the cell are able to interact with it surrounding, including bacterial and viral interaction. In the joints, glycoproteins are responsible for lubrication, and in our gastrointestinal tract, glycoproteins sustain a healthy symbiotic relation between the microbes in our gut and us humans as their host.
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GLYCOSTAR are addressing two specific aspects of glycosylation and OA:
1) Understanding the pathway that leads to the decreased lubrication found in OA patients. The short-term objective is to identify biomarkers that can be used for early detection of lubrication deficient OA patient. The long term is to specifically target these patients with treatment that will boost their lubrication and retrieve their joint function.
2) Exploring a connection between OA and an unhealthy gut microbiota (dysbiosis). We explore the microbiome of OA patients to identify proinflammatory microbes that are capable of disrupting the intricate interplay between the mucus glycoproteins in the gut and the gut microbiome. The long- term outcome of this project is to develop nutritional guidelines for a population that displays an OA microbiota endotype. By a nutritional intervention we believe that we can restore a healthy microflora of these individuals, halting deterioration of the joints.
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Andersson E, Tykesson E, Lohmander LS, Karlsson NG, Jin C, Mirgorodskaya E, Swärd P, Struglics A.Quantification of chondroitin sulfate, hyaluronic acid and N-glycans in synovial fluid - A technical performance study. Osteoarthr Cartil Open. 2023 Sep;5(3):100380. doi: 10.1016/j.ocarto.2023.100380. eCollection 2023 Sep. PubMed PMID: 37426292; PubMed Central PMCID: PMC10322674.
Elsaid K, Merriman TR, Rossitto LA, Liu-Bryan R, Karsh J, Phipps-Green A, Jay GD, Elsayed S, Qadri M, Miner M, Cadzow M, Dambruoso TJ, Schmidt TA, Dalbeth N, Chhana A, Höglund J, Ghassemian M, Campeau A, Maltez N, Karlsson NG, Gonzalez DJ, Terkeltaub R. Amplification of Inflammation by Lubricin Deficiency Implicated in Incident, Erosive Gout Independent of Hyperuricemia. Arthritis Rheumatol. 2023 May;75(5):794-805. doi: 10.1002/art.42413. Epub 2023 Mar 10. PubMed PMID: 36457235; PubMed Central PMCID: PMC10191887.
Shuoker B, Pichler MJ, Jin C, Sakanaka H, Wu H, Gascueña AM, Liu J, Nielsen TS, Holgersson J, Nordberg Karlsson E, Juge N, Meier S, Morth JP, Karlsson NG, Abou Hachem M. Sialidases and fucosidases of Akkermansia muciniphila are crucial for growth on mucin and nutrient sharing with mucus-associated gut bacteria. Nat Commun. 2023 Apr 1;14(1):1833. doi: 10.1038/s41467-023-37533-6. PubMed PMID: 37005422; PubMed Central PMCID: PMC10067855.
Huang S, Thomsson KA, Jin C, Ryberg H, Das N, Struglics A, Rolfson O, Björkman LI, Eisler T, Schmidt TA, Jay GD, Krawetz R, Karlsson NG. Truncated lubricin glycans in osteoarthritis stimulate the synoviocyte secretion of VEGFA, IL-8, and MIP-1α: Interplay between O-linked glycosylation and inflammatory cytokines. Front Mol Biosci. 2022;9:942406. doi: 10.3389/fmolb.2022.942406. eCollection 2022. PubMed PMID: 36213120; PubMed Central PMCID: PMC9532613.
Luis AS, Baslé A, Byrne DP, Wright GSA, London JA, Jin C, Karlsson NG, Hansson GC, Eyers PA, Czjzek M, Barbeyron T, Yates EA, Martens EC, Cartmell A. Sulfated glycan recognition by carbohydrate sulfatases of the human gut microbiota. Nat Chem Biol. 2022 Aug;18(8):841-849. doi: 10.1038/s41589-022-01039-x. Epub 2022 Jun 16. PubMed PMID: 35710619; PubMed Central PMCID: PMC7613211.
Luis AS, Jin C, Pereira GV, Glowacki RWP, Gugel SR, Singh S, Byrne DP, Pudlo NA, London JA, Baslé A, Reihill M, Oscarson S, Eyers PA, Czjzek M, Michel G, Barbeyron T, Yates EA, Hansson GC, Karlsson NG, Cartmell A, Martens EC. A single sulfatase is required to access colonic mucin by a gut bacterium. Nature.2021 Oct;598(7880):332-337. doi: 10.1038/s41586-021-03967-5. Epub 2021 Oct 6. PubMed PMID: 34616040; PubMed Central PMCID: PMC9128668.
Flowers SA, Thomsson KA, Ali L, Huang S, Mthembu Y, Regmi SC, Holgersson J, Schmidt TA, Rolfson O, Björkman LI, Sundqvist M, Karlsson-Bengtsson A, Jay GD, Eisler T, Krawetz R, Karlsson NG. Decrease of core 2 O-glycans on synovial lubricin in osteoarthritis reduces galectin-3 mediated crosslinking. J Biol Chem. 2020 Nov 20;295(47):16023-16036. doi: 10.1074/jbc.RA120.012882. Epub 2020 Sep 14. PubMed PMID: 32928962; PubMed Central PMCID: PMC7681006.
Pichler MJ, Yamada C, Shuoker B, Alvarez-Silva C, Gotoh A, Leth ML, Schoof E, Katoh T, Sakanaka M, Katayama T, Jin C, Karlsson NG, Arumugam M, Fushinobu S, Abou Hachem M. Butyrate producing colonic Clostridiales metabolise human milk oligosaccharides and cross feed on mucin via conserved pathways.Nat Commun. 2020 Jul 3;11(1):3285. doi: 10.1038/s41467-020-17075-x. PubMed PMID: 32620774; PubMed Central PMCID: PMC7335108.
Nagao-Kitamoto H, Leslie JL, Kitamoto S, Jin C, Thomsson KA, Gillilland MG 3rd, Kuffa P, Goto Y, Jenq RR, Ishii C, Hirayama A, Seekatz AM, Martens EC, Eaton KA, Kao JY, Fukuda S, Higgins PDR, Karlsson NG, Young VB, Kamada N. Interleukin-22-mediated host glycosylation prevents Clostridioides difficile infection by modulating the metabolic activity of the gut microbiota. Nat Med. 2020 Apr;26(4):608-617. doi: 10.1038/s41591-020-0764-0. Epub 2020 Feb 17. PubMed PMID: 32066975; PubMed Central PMCID: PMC7160049.
Huang S, Thomsson KA, Jin C, Alweddi S, Struglics A, Rolfson O, Björkman LI, Kalamajski S, Schmidt TA, Jay GD, Krawetz R, Karlsson NG, Eisler T. Cathepsin g Degrades Both Glycosylated and Unglycosylated Regions of Lubricin, a Synovial Mucin. Sci Rep. 2020 Mar 6;10(1):4215. doi: 10.1038/s41598-020-61161-5. PubMed PMID: 32144329; PubMed Central PMCID: PMC7060204.
Flowers SA, Zieba A, Örnros J, Jin C, Rolfson O, Björkman LI, Eisler T, Kalamajski S, Kamali-Moghaddam M, Karlsson NG. Lubricin binds cartilage proteins, cartilage oligomeric matrix protein, fibronectin and collagen II at the cartilage surface. Sci Rep. 2017 Oct 13;7(1):13149. doi: 10.1038/s41598-017-13558-y. PubMed PMID: 29030641; PubMed Central PMCID: PMC5640667.
Flowers SA, Kalamajski S, Ali L, Björkman LI, Raj JR, Aspberg A, Karlsson NG, Jin C. Cartilage oligomeric matrix protein forms protein complexes with synovial lubricin via non-covalent and covalent interactions.Osteoarthritis Cartilage. 2017 Sep;25(9):1496-1504. doi: 10.1016/j.joca.2017.03.016. Epub 2017 Apr 1. PubMed PMID: 28373131.
Svala E, Jin C, Rüetschi U, Ekman S, Lindahl A, Karlsson NG, Skiöldebrand E. Characterisation of lubricin in synovial fluid from horses with osteoarthritis. Equine Vet J. 2017 Jan;49(1):116-123. doi: 10.1111/evj.12521. Epub 2015 Dec 16. PubMed PMID: 26507102.
Ali L, Flowers SA, Jin C, Bennet EP, Ekwall AK, Karlsson NG. The O-glycomap of lubricin, a novel mucin responsible for joint lubrication, identified by site-specific glycopeptide analysis. Mol Cell Proteomics.2014 Dec;13(12):3396-409. doi: 10.1074/mcp.M114.040865. Epub 2014 Sep 3. PubMed PMID: 25187573; PubMed Central PMCID: PMC4256492.
Jin C, Ekwall AK, Bylund J, Björkman L, Estrella RP, Whitelock JM, Eisler T, Bokarewa M, Karlsson NG.Human synovial lubricin expresses sialyl Lewis x determinant and has L-selectin ligand activity. J Biol Chem. 2012 Oct 19;287(43):35922-33. doi: 10.1074/jbc.M112.363119. Epub 2012 Aug 28. PubMed PMID: 22930755; PubMed Central PMCID: PMC3476260.
Lord MS, Estrella RP, Chuang CY, Youssef P, Karlsson NG, Flannery CR, Whitelock JM. Not all lubricin isoforms are substituted with a glycosaminoglycan chain. Connect Tissue Res. 2012;53(2):132-41. doi: 10.3109/03008207.2011.614364. Epub 2011 Oct 3. PubMed PMID: 21966936.
strella RP, Whitelock JM, Packer NH, Karlsson NG. The glycosylation of human synovial lubricin: implications for its role in inflammation. Biochem J. 2010 Jul 15;429(2):359-67. doi: 10.1042/BJ20100360. PubMed PMID: 20443780.