Biglycan neo-epitope (BGN262), a novel biomarker for screening early changes in equine osteoarthritic subchondral bone.
Abstract: Native biglycan (BGN), which can undergo proteolytic cleavage in pathological conditions, is well known to be involved in bone formation and mineralization. This study aimed to delineate the specific cleavage fragment, a neo-epitope for BGN (BGN), in synovial fluid (SF) from young racehorses in training, osteoarthritic (OA) joints with subchondral bone sclerosis (SCBS), and chip fracture joints. A custom-made inhibition ELISA was developed to quantify BGN in SF. Cohort 1: A longitudinal study comprising 10 racehorses undergoing long-term training. Cohort 2: A cross-sectional study comprising joints from horses (N = 69) with different stages of OA and radiographically classified SCBS. Cohort 3: A cross-sectional study comprising horses (N = 9) with chip fractures. Receiver operating characteristic (ROC) curve analysis was performed (healthy joints vs chip joints) to evaluate BGN robustness. Cohort 1: SF BGN levels from racehorses showed a statistical increase during the first 6 months of the training period. Cohort 2: BGN levels were significantly higher in the SF from severe SCBS joints. Cohort 3: SF BGN levels in chip fracture joints showed a significant increase compared to normal joints. The ROC analysis showed an AUC of 0.957 (95% C.I 0.868-1.046), indicating good separation between the groups. The data presented show that BGN levels increase in SF in correlation with the initiation of training, severity of SCBS, and presence of chip fractures. This suggests that BGN is a potential predictor and a novel biomarker for early changes in subchondral bone (SCB), aiming to prevent catastrophic injuries in racehorses.
Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Publication Date: 2022-07-21 PubMed ID: 35870736DOI: 10.1016/j.joca.2022.07.005Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The study investigates the use of a novel biomarker, Biglycan neo-epitope (BGN262), to screen for early osteoarthritic changes in horses’ subchondral bone. Researchers have found that BGN levels increase with the initiation of training, severity of subchondral bone sclerosis, and presence of chip fractures.
Objective of the Study
- This study aims to delineate the specific cleavage fragment, a neo-epitope for biglycan (BGN), which is known to be involved in bone formation and mineralization.
- The researchers hypothesized that BGN levels increase significantly in horses undergoing long-term training, those with osteoarthritis, subchondral bone sclerosis, and chip fractures.
Methodology
- Researchers developed custom-made inhibition ELISA to quantify BGN levels in synovial fluid (SF) of horses.
- Three cohorts were studied: the first was a longitudinal study involving 10 racehorses undergoing long term training; the second was a cross-sectional study of joints from horses at different OA stages; and the third was a cross-sectional study involving horses with chip fractures.
Findings
- In the first cohort, researchers found statistical evidence to suggest that BGN levels in SF from horses increase during the initial six months of training.
- In the second cohort, the researchers found that BGN levels were significantly higher in SF from severe SCBS joints.
- In the third cohort, there was a significant increase in SF BGN levels in chip fracture joints compared to normal joints.
Conclusion
- The researchers concluded that BGN levels increase in SF in correlation with the initiation of training, severity of subchondral bone sclerosis, and presence of chip fractures.
- The receiver operating characteristic curve analysis showed good separation between the groups, suggesting that BGN is a potential predictor and novel biomarker for early changes in subchondral bone.
- The findings also suggest that BGN could be used as a screening tool to prevent catastrophic injuries in racehorses.
Cite This Article
APA
Adepu S, Ekman S, Leth J, Johansson U, Lindahl A, Skiöldebrand E.
(2022).
Biglycan neo-epitope (BGN262), a novel biomarker for screening early changes in equine osteoarthritic subchondral bone.
Osteoarthritis Cartilage, 30(10), 1328-1336.
https://doi.org/10.1016/j.joca.2022.07.005 Publication
Researcher Affiliations
- Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala, Sweden. Electronic address: saritha.adepu@slu.se.
- Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala, Sweden. Electronic address: stina.ekman@slu.se.
- Department of Energy and Technology, Unit of Applied Statistics and Mathematics, Swedish University of Agricultural Sciences, Uppsala, Sweden. Electronic address: jakob.leth@slu.se.
- Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala, Sweden. Electronic address: ulrika.johansson@corline.se.
- Clinical Chemistry and Transfusion Medicine, Sahlgrenska University Hospital, Gothenburg Sweden. Electronic address: anders.lindahl@clinchem.gu.se.
- Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala, Sweden. Electronic address: eva.skioldebrand@slu.se.
MeSH Terms
- Animals
- Biglycan
- Biomarkers
- Cross-Sectional Studies
- Epitopes
- Horse Diseases
- Horses
- Humans
- Longitudinal Studies
Conflict of Interest Statement
Conflcit of interest SE, AL, and ES are stakeholders of SGPTH Life Science holding the patent covering the BGN (262) neo-epitope. The other co-authors have no conflicts of interest to declare.
Citations
This article has been cited 2 times.- Skiöldebrand E, Adepu S, Lützelschwab C, Nyström S, Lindahl A, Abrahamsson-Aurell K, Hansson E. A randomized, triple-blinded controlled clinical study with a novel disease-modifying drug combination in equine lameness-associated osteoarthritis.. Osteoarthr Cartil Open 2023 Sep;5(3):100381.
- Adepu S, Lord M, Hugoh Z, Nyström S, Mattsson-Hulten L, Abrahamsson-Aurell K, Lützelschwab C, Skiöldebrand E. Salivary biglycan-neo-epitope-BGN(262): 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 2023 Jun;5(2):100354.
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