Analyze Diet
Osteoarthritis and cartilage open2023; 5(2); 100354; doi: 10.1016/j.ocarto.2023.100354

Salivary biglycan-neo-epitope-BGN262: A novel surrogate biomarker for equine osteoarthritic sub-chondral bone sclerosis and to monitor the effect of short-term training and surface arena.

Abstract: We aimed to delineate a novel soluble Biglycan Neo-epitope-BGN262 in saliva from young reference and osteoarthritic horses in conjunction with the influence of short-term training exercise, riding surface hardness, circadian rhythm, and feeding on its soluble levels. Unassigned: A custom-made inhibition ELISA was used for the quantification of BGN262 in saliva. Cohort 1: A cross-sectional study comprising reference (N ​= ​19) and OA horses (N ​= ​9) with radiographically classified subchondral bone sclerosis. Receiver operating characteristic curve analysis was performed to evaluate the robustness of BGN262. Cohorts 2 (N ​= ​5) & 3 (N ​= ​7): Longitudinal studies of sampling during a short-term training exercise (sand-fibre) and a cross-over design of short-training exercise on 2 different riding arenas (sand and sand-fibre), respectively. Capillary western immunoassay was used to determine the BGN262 molecular size in a selection of saliva samples collected from cohort 1. Unassigned: Cohort 1: Salivary BGN262 levels were significantly higher in the OA group. The Receiver operating characteristic curve analysis showed an area under the curve of 0.8304 [0.6386 to 1.022], indicating a good separation from the reference group. Cohorts 2 & 3: Salivary BGN262 levels significantly changed during the exercise on sand and sand-fibre arena, with a trend towards higher levels for sand-fibre. The size of the BGN262 fragment determined by Capillary western assay was 18 ​kDa. Unassigned: The data presented show saliva BGN262 levels as a novel biomarker in evaluating the influence of exercise, and interaction with riding arenas alongside assessing osteoarthritis severity.
Publication Date: 2023-03-15 PubMed ID: 36968250PubMed Central: PMC10033749DOI: 10.1016/j.ocarto.2023.100354Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research aimed to identify a new biomarker found in saliva, called Biglycan Neo-epitope-BGN262, that may help evaluate exercise impact, arena riding interaction, and the severity of osteoarthritis, particularly subchondral bone sclerosis, in horses.

Background

  • The study focused on Biglycan Neo-epitope-BGN262 (BGN262), a protein fragment found in saliva.
  • Research aimed to understand BGN262’s behavior relative to short-term exercise, the hardness of riding surfaces, circadian rhythms, and feeding.
  • The researchers also investigated whether BGN262 levels could indicate the presence and the severity of osteoarthritis, particularly subchondral bone sclerosis, in horses.

Methodology

  • An enzyme-linked immunosorbent assay (ELISA), a commonly used lab test to measure the concentration of substances such as proteins and hormones in body fluids, was used to quantify BGN262 in equine saliva.
  • The study included a cross-sectional study (Cohort 1) which consisted of a reference group (19 horses) and an osteoarthritic (OA) group (9 horses) to compare BGN262 levels.
  • Additionally, two longitudinal studies (Cohorts 2 and 3) were conducted, involving a training exercise and a cross-over test between two different types of riding arenas, respectively.
  • The size of the BGN262 fragment was determined using a Capillary Western Assay, a method used to measure proteins in samples.

Findings

  • Salivary BGN262 levels were significantly higher in horses with OA.
  • The use of the Receiver Operating Characteristic (ROC) curve, a measure of the robustness of BGN262, showed good separation from the reference group.
  • Salivary levels of BGN262 also changed significantly during exercises conducted on sand and sand-fibre arenas, and they tended to be higher on sand-fibre.

Implications

  • Results suggested that BGN262 levels can serve as a new biomarker to evaluate the impact of exercise and interaction with various riding arenas on horses.
  • Moreover, the study demonstrated that higher levels of BGN262 in saliva might indicate the severity of osteoarthritis in horses.

Cite This Article

APA
Adepu S, Lord M, Hugoh Z, Nyström S, Mattsson-Hulten L, Abrahamsson-Aurell K, Lützelschwab C, Skiöldebrand E. (2023). Salivary biglycan-neo-epitope-BGN262: A novel surrogate biomarker for equine osteoarthritic sub-chondral bone sclerosis and to monitor the effect of short-term training and surface arena. Osteoarthr Cartil Open, 5(2), 100354. https://doi.org/10.1016/j.ocarto.2023.100354

Publication

ISSN: 2665-9131
NlmUniqueID: 101767068
Country: England
Language: English
Volume: 5
Issue: 2
Pages: 100354
PII: 100354

Researcher Affiliations

Adepu, S
  • Department of Pathology, Institute of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Lord, M
  • Department of Physics, Chalmers University of Technology, Gothenburg, Sweden.
Hugoh, Z
  • Department of Physics, Chalmers University of Technology, Gothenburg, Sweden.
Nyström, S
  • Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, Sahlgrenska University Hospital, Gothenburg University, Gothenburg, Sweden.
Mattsson-Hulten, L
  • Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, Sahlgrenska University Hospital, Gothenburg University, Gothenburg, Sweden.
Abrahamsson-Aurell, K
  • Hallands Djursjukhus Kungsbacka Hästklinik, Älvsåkers Byväg 20, 434 95 Kungsbacka, Sweden.
Lützelschwab, C
  • Department of Pathology, Institute of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Skiöldebrand, E
  • Department of Pathology, Institute of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala, Sweden.

Conflict of Interest Statement

ES and LMH are among the stakeholders of SGPTH Life Science holding the patent covering the BGN262 neo-epitope. The other co-authors have no conflicts of interest to declare.

References

This article includes 50 references
  1. Vincent TL. Of mice and men: converging on a common molecular understanding of osteoarthritis.. Lancet Rheumatol 2020 Oct;2(10):e633-e645.
  2. Lories RJ, Luyten FP. The bone-cartilage unit in osteoarthritis.. Nat Rev Rheumatol 2011 Jan;7(1):43-9.
    pubmed: 21135881doi: 10.1038/nrrheum.2010.197google scholar: lookup
  3. Hitchens PL, Morrice-West AV, Stevenson MA, Whitton RC. Meta-analysis of risk factors for racehorse catastrophic musculoskeletal injury in flat racing.. Vet J 2019 Mar;245:29-40.
    pubmed: 30819423doi: 10.1016/j.tvjl.2018.11.014google scholar: lookup
  4. Te Moller NCR, van Weeren PR. How exercise influences equine joint homeostasis.. Vet J 2017 Apr;222:60-67.
    pubmed: 28392152doi: 10.1016/j.tvjl.2017.03.004google scholar: lookup
  5. Hu W, Chen Y, Dou C, Dong S. Microenvironment in subchondral bone: predominant regulator for the treatment of osteoarthritis.. Ann Rheum Dis 2021 Apr;80(4):413-422.
  6. Goldring SR, Goldring MB. Changes in the osteochondral unit during osteoarthritis: structure, function and cartilage-bone crosstalk.. Nat Rev Rheumatol 2016 Nov;12(11):632-644.
    pubmed: 27652499doi: 10.1038/nrrheum.2016.148google scholar: lookup
  7. Bianco P, Fisher LW, Young MF, Termine JD, Robey PG. Expression and localization of the two small proteoglycans biglycan and decorin in developing human skeletal and non-skeletal tissues.. J Histochem Cytochem 1990 Nov;38(11):1549-63.
    pubmed: 2212616doi: 10.1177/38.11.2212616google scholar: lookup
  8. Miguez PA. Evidence of biglycan structure-function in bone homeostasis and aging.. Connect Tissue Res 2020 Jan;61(1):19-33.
    pubmed: 31597498doi: 10.1080/03008207.2019.1669577google scholar: lookup
  9. Kram V, Shainer R, Jani P, Meester JAN, Loeys B, Young MF. Biglycan in the Skeleton.. J Histochem Cytochem 2020 Nov;68(11):747-762.
    pmc: PMC7649967pubmed: 32623936doi: 10.1369/0022155420937371google scholar: lookup
  10. Hua R, Ni Q, Eliason TD, Han Y, Gu S, Nicolella DP, Wang X, Jiang JX. Biglycan and chondroitin sulfate play pivotal roles in bone toughness via retaining bound water in bone mineral matrix.. Matrix Biol 2020 Dec;94:95-109.
  11. Han B, Li Q, Wang C, Chandrasekaran P, Zhou Y, Qin L, Liu XS, Enomoto-Iwamoto M, Kong D, Iozzo RV, Birk DE, Han L. Differentiated activities of decorin and biglycan in the progression of post-traumatic osteoarthritis.. Osteoarthritis Cartilage 2021 Aug;29(8):1181-1192.
    pmc: PMC8319061pubmed: 33915295doi: 10.1016/j.joca.2021.03.019google scholar: lookup
  12. Genovese F, Barascuk N, Larsen L, Larsen MR, Nawrocki A, Li Y, Zheng Q, Wang J, Veidal SS, Leeming DJ, Karsdal MA. Biglycan fragmentation in pathologies associated with extracellular matrix remodeling by matrix metalloproteinases.. Fibrogenesis Tissue Repair 2013 May 1;6(1):9.
    pmc: PMC3651402pubmed: 23635022doi: 10.1186/1755-1536-6-9google scholar: lookup
  13. Barreto G, Soininen A, Ylinen P, Sandelin J, Konttinen YT, Nordström DC, Eklund KK. Soluble biglycan: a potential mediator of cartilage degradation in osteoarthritis.. Arthritis Res Ther 2015 Dec 24;17:379.
    pmc: PMC4718039pubmed: 26703441doi: 10.1186/s13075-015-0902-0google scholar: lookup
  14. Adepu S, Ekman S, Leth J, Johansson U, Lindahl A, Skiöldebrand E. Biglycan neo-epitope (BGN(262)), a novel biomarker for screening early changes in equine osteoarthritic subchondral bone.. Osteoarthritis Cartilage 2022 Oct;30(10):1328-1336.
    pubmed: 35870736doi: 10.1016/j.joca.2022.07.005google scholar: lookup
  15. Crevier-Denoix N, Audigié F, Emond AL, Dupays AG, Pourcelot P, Desquilbet L, Chateau H, Denoix JM. Effect of track surface firmness on the development of musculoskeletal injuries in French Trotters during four months of harness race training.. Am J Vet Res 2017 Nov;78(11):1293-1304.
    pubmed: 29076363doi: 10.2460/ajvr.78.11.1293google scholar: lookup
  16. Egenvall A, Roepstorff L, Peterson M, Lundholm M, Hernlund E. The Descriptions and Attitudes of Riders and Arena Owners to 656 Equestrian Sport Surfaces in Sweden.. Front Vet Sci 2021;8:798910.
    pmc: PMC8732755pubmed: 35004931doi: 10.3389/fvets.2021.798910google scholar: lookup
  17. Hernlund E, Egenvall A, Hobbs SJ, Peterson ML, Northrop AJ, Bergh A, Martin JH, Roepstorff L. Comparing subjective and objective evaluation of show jumping competition and warm-up arena surfaces.. Vet J 2017 Sep;227:49-57.
    pubmed: 29031331doi: 10.1016/j.tvjl.2017.09.001google scholar: lookup
  18. Svala E, Löfgren M, Sihlbom C, Rüetschi U, Lindahl A, Ekman S, Skiöldebrand E. An inflammatory equine model demonstrates dynamic changes of immune response and cartilage matrix molecule degradation in vitro.. Connect Tissue Res 2015;56(4):315-25.
    pubmed: 25803623doi: 10.3109/03008207.2015.1027340google scholar: lookup
  19. He Y, Manon-Jensen T, Arendt-Nielsen L, Petersen KK, Christiansen T, Samuels J, Abramson S, Karsdal MA, Attur M, Bay-Jensen AC. Potential diagnostic value of a type X collagen neo-epitope biomarker for knee osteoarthritis.. Osteoarthritis Cartilage 2019 Apr;27(4):611-620.
    pubmed: 30654118doi: 10.1016/j.joca.2019.01.001google scholar: lookup
  20. McIlwraith CW, Kawcak CE, Frisbie DD, Little CB, Clegg PD, Peffers MJ, Karsdal MA, Ekman S, Laverty S, Slayden RA, Sandell LJ, Lohmander LS, Kraus VB. Biomarkers for equine joint injury and osteoarthritis.. J Orthop Res 2018 Mar;36(3):823-831.
    pubmed: 28921609doi: 10.1002/jor.23738google scholar: lookup
  21. Vieira FAC, Baccarin RYA, Aguiar JAK, Michelacci YM. Urinary excretion of glycosaminoglycans in horses: changes with age, training, and osteoarthritis.. J. Equine Vet. Sci. 2005;25:387–400.
  22. Drobitch RK, Svensson CK. Therapeutic drug monitoring in saliva. An update.. Clin Pharmacokinet 1992 Nov;23(5):365-79.
  23. Fischer HP, Eich W, Russell IJ. A possible role for saliva as a diagnostic fluid in patients with chronic pain.. Semin Arthritis Rheum 1998 Jun;27(6):348-59.
    pubmed: 9662753doi: 10.1016/s0049-0172(98)80014-0google scholar: lookup
  24. Jasim H, Carlsson A, Hedenberg-Magnusson B, Ghafouri B, Ernberg M. Saliva as a medium to detect and measure biomarkers related to pain.. Sci Rep 2018 Feb 19;8(1):3220.
    pmc: PMC5818517pubmed: 29459715doi: 10.1038/s41598-018-21131-4google scholar: lookup
  25. Peterson ML, Wayne McIlwraith C, Reiser RF. Development of a system for the in-situ characterisation of thoroughbred horse racing track surfaces.. Biosyst. Eng. 2008;101:260–269.
  26. Latham CM, Owen RN, Dickson EC, Guy CP, White-Springer SH. Skeletal Muscle Adaptations to Exercise Training in Young and Aged Horses.. Front Aging 2021;2:708918.
    pmc: PMC9261331pubmed: 35822026doi: 10.3389/fragi.2021.708918google scholar: lookup
  27. Kawcak CE, McIlwraith CW, Firth EC. Effects of early exercise on metacarpophalangeal joints in horses.. Am J Vet Res 2010 Apr;71(4):405-11.
    pubmed: 20367048doi: 10.2460/ajvr.71.4.405google scholar: lookup
  28. Murray RC, Branch MV, Dyson SJ, Parkin TD, Goodship AE. How does exercise intensity and type affect equine distal tarsal subchondral bone thickness?. J Appl Physiol (1985) 2007 Jun;102(6):2194-200.
  29. Parkes RS, Witte TH. The foot-surface interaction and its impact on musculoskeletal adaptation and injury risk in the horse.. Equine Vet J 2015 Sep;47(5):519-25.
    pubmed: 25640598doi: 10.1111/evj.12420google scholar: lookup
  30. Zhang CZ, Cheng XQ, Li JY, Zhang P, Yi P, Xu X, Zhou XD. Saliva in the diagnosis of diseases.. Int J Oral Sci 2016 Sep 29;8(3):133-7.
    pmc: PMC5113094pubmed: 27585820doi: 10.1038/ijos.2016.38google scholar: lookup
  31. Jacobsen S, Top Adler DM, Bundgaard L, Sørensen MA, Andersen PH, Bendixen E. The use of liquid chromatography tandem mass spectrometry to detect proteins in saliva from horses with and without systemic inflammation.. Vet J 2014 Dec;202(3):483-8.
    pubmed: 25296850doi: 10.1016/j.tvjl.2014.08.032google scholar: lookup
  32. Naesse EP, Schreurs O, Messelt E, Hayashi K, Schenck K. Distribution of nerve growth factor, pro-nerve growth factor, and their receptors in human salivary glands.. Eur J Oral Sci 2013 Feb;121(1):13-20.
    pubmed: 23331419doi: 10.1111/eos.12008google scholar: lookup
  33. Lightbody KL, Matthews JB, Kemp-Symonds JG, Lambert PA, Austin CJ. Use of a saliva-based diagnostic test to identify tapeworm infection in horses in the UK.. Equine Vet J 2018 Mar;50(2):213-219.
    pubmed: 28805265doi: 10.1111/evj.12742google scholar: lookup
  34. Contreras-Aguilar MD, Henry S, Coste C, Tecles F, Escribano D, Cerón JJ, Hausberger M. Changes in Saliva Analytes Correlate with Horses' Behavioural Reactions to An Acute Stressor: A Pilot Study.. Animals (Basel) 2019 Nov 18;9(11).
    pmc: PMC6912570pubmed: 31752194doi: 10.3390/ani9110993google scholar: lookup
  35. Mazor M, Best TM, Cesaro A, Lespessailles E, Toumi H. Osteoarthritis biomarker responses and cartilage adaptation to exercise: A review of animal and human models.. Scand J Med Sci Sports 2019 Aug;29(8):1072-1082.
    pubmed: 31033061doi: 10.1111/sms.13435google scholar: lookup
  36. Kang OD, Lee WS. Changes in Salivary Cortisol Concentration in Horses during Different Types of Exercise.. Asian-Australas J Anim Sci 2016 May;29(5):747-52.
    pmc: PMC4852239pubmed: 26954193doi: 10.5713/ajas.16.0009google scholar: lookup
  37. Bazzano M, Laghi L, Zhu C, Lotito E, Sgariglia S, Tesei B, Laus F. Exercise Induced Changes in Salivary and Serum Metabolome in Trained Standardbred, Assessed by (1)H-NMR.. Metabolites 2020 Jul 21;10(7).
    pmc: PMC7407172pubmed: 32708237doi: 10.3390/metabo10070298google scholar: lookup
  38. Tékus E, Kaj M, Szabó E, Szénási NL, Kerepesi I, Figler M, Gábriel R, Wilhelm M. Comparison of blood and saliva lactate level after maximum intensity exercise.. Acta Biol Hung 2012;63 Suppl 1:89-98.
  39. Bandhakavi S, Stone MD, Onsongo G, Van Riper SK, Griffin TJ. A dynamic range compression and three-dimensional peptide fractionation analysis platform expands proteome coverage and the diagnostic potential of whole saliva.. J Proteome Res 2009 Dec;8(12):5590-600.
    pmc: PMC2789208pubmed: 19813771doi: 10.1021/pr900675wgoogle scholar: lookup
  40. Lundström T, Lingström P, Wattle O, Carlén A, Birkhed D. Equine saliva components during mastication, and in vivo pH changes in the oral biofilm of sound and carious tooth surfaces after sucrose exposure.. Acta Vet Scand 2020 May 23;62(1):21.
    pmc: PMC7245034pubmed: 32446309doi: 10.1186/s13028-020-00518-2google scholar: lookup
  41. Humphrey SP, Williamson RT. A review of saliva: normal composition, flow, and function.. J Prosthet Dent 2001 Feb;85(2):162-9.
    pubmed: 11208206doi: 10.1067/mpr.2001.113778google scholar: lookup
  42. Rudney JD, Ji Z, Larson CJ. The prediction of saliva swallowing frequency in humans from estimates of salivary flow rate and the volume of saliva swallowed.. Arch Oral Biol 1995 Jun;40(6):507-12.
    pubmed: 7677595doi: 10.1016/0003-9969(95)00004-9google scholar: lookup
  43. Contreras-Aguilar MD, Hevia ML, Escribano D, Lamy E, Tecles F, Cerón JJ. Effect of food contamination and collection material in the measurement of biomarkers in saliva of horses.. Res Vet Sci 2020 Apr;129:90-95.
    pubmed: 31954319doi: 10.1016/j.rvsc.2020.01.006google scholar: lookup
  44. Glim JE, Everts V, Niessen FB, Ulrich MM, Beelen RH. Extracellular matrix components of oral mucosa differ from skin and resemble that of foetal skin.. Arch Oral Biol 2014 Oct;59(10):1048-55.
  45. Honardoust D, Eslami A, Larjava H, Häkkinen L. Localization of small leucine-rich proteoglycans and transforming growth factor-beta in human oral mucosal wound healing.. Wound Repair Regen 2008 Nov-Dec;16(6):814-23.
  46. Lončar-Brzak B, Klobučar M, Veliki-Dalić I, Sabol I, Kraljević Pavelić S, Krušlin B, Mravak-Stipetić M. Expression of small leucine-rich extracellular matrix proteoglycans biglycan and lumican reveals oral lichen planus malignant potential.. Clin Oral Investig 2018 Mar;22(2):1071-1082.
    pubmed: 28779221doi: 10.1007/s00784-017-2190-3google scholar: lookup
  47. Karsdal MA, Henriksen K, Leeming DJ, Woodworth T, Vassiliadis E, Bay-Jensen AC. Novel combinations of Post-Translational Modification (PTM) neo-epitopes provide tissue-specific biochemical markers--are they the cause or the consequence of the disease?. Clin Biochem 2010 Jul;43(10-11):793-804.
  48. Genovese F, Karsdal MA. Protein degradation fragments as diagnostic and prognostic biomarkers of connective tissue diseases: understanding the extracellular matrix message and implication for current and future serological biomarkers.. Expert Rev Proteomics 2016;13(2):213-25.
    pubmed: 26689914doi: 10.1586/14789450.2016.1134327google scholar: lookup
  49. Bhutada S, Li L, Willard B, Muschler G, Piuzzi N, Apte SS. Forward and reverse degradomics defines the proteolytic landscape of human knee osteoarthritic cartilage and the role of the serine protease HtrA1.. Osteoarthritis Cartilage 2022 Aug;30(8):1091-1102.
    pubmed: 35339693doi: 10.1016/j.joca.2022.02.622google scholar: lookup
  50. Mohamed R, Campbell JL, Cooper-White J, Dimeski G, Punyadeera C. The impact of saliva collection and processing methods on CRP, IgE, and Myoglobin immunoassays.. Clin Transl Med 2012 Sep 5;1(1):19.
    pmc: PMC3560976pubmed: 23369566doi: 10.1186/2001-1326-1-19google scholar: lookup

Citations

This article has been cited 3 times.
  1. Smith MM, Melrose J. COMP Is a Biomarker of Cartilage Destruction, Extracellular Matrix and Vascular Remodeling and Tissue Repair. Int J Mol Sci 2025 Sep 19;26(18).
    doi: 10.3390/ijms26189182pubmed: 41009743google scholar: lookup
  2. Zhu M, Wu SCM, Tam WK, Wong CK, Liao P, Cheah KS, Chan D, James AW, Leung VY. Biglycan fragment modulates TGF-β activity in intervertebral disc via an eIF6-coupled intracellular path. Sci Adv 2025 Feb 14;11(7):eadq8545.
    doi: 10.1126/sciadv.adq8545pubmed: 39951526google scholar: lookup
  3. Welhaven HD, Welfley AH, June RK. Osteoarthritis Year in Review 2024: Molecular biomarkers of osteoarthritis. Osteoarthritis Cartilage 2025 Jan;33(1):67-87.
    doi: 10.1016/j.joca.2024.10.003pubmed: 39427749google scholar: lookup