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Abstract

Integrating Articular Cartilage Histopathology with CTX-II and COMP as Synovial Fluid Biomarkers for a Comprehensive Analysis in Osteoarthritis Evaluation †

by
Sofija Semenistaja
1,*,
Lība Sokolovska
2,
Pēteris Studers
3,4,
Anda Kadiša
5,
Valērija Groma
6 and
Sandra Skuja
6
1
Department of Doctoral Studies, Rīga Stradiņš University, LV-1007 Riga, Latvia
2
Institute of Microbiology and Virology, Rīga Stradiņš University, Rātsupītes St. 5, LV-1067 Riga, Latvia
3
Joint Laboratory of Traumatology and Orthopaedics, Rīga Stradiņš University, LV-1005 Riga, Latvia
4
Hospital of Traumatology and Orthopaedics, Duntes St. 22, LV-1005 Riga, Latvia
5
Department of Internal Diseases, Rīga Stradiņš University, LV-1007 Riga, Latvia
6
Joint Laboratory of Electron Microscopy, Institute of Anatomy and Anthropology, Rīga Stradiņš University, Kronvalda blvd 9, LV-1010 Riga, Latvia
*
Author to whom correspondence should be addressed.
†
Presented at the 3rd International Electronic Conference on Biomolecules, 23–25 April 2024; Available online: https://sciforum.net/event/IECBM2024.
Proceedings 2024, 103(1), 38; https://doi.org/10.3390/proceedings2024103038
Published: 12 April 2024
(This article belongs to the Proceedings of The 3rd International Electronic Conference on Biomolecules)
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Versions Notes

1. Introduction

Osteoarthritis (OA) is the most common form of chronic joint disease characterized by the loss of cartilage as the primary site of the lesion. Both collagenous and non-collagenous proteins of the extracellular matrix (ECM) are dysregulated by the cellular component damage. Alterations in cartilage composition may manifest through variations in synovial fluid concentrations of C-terminal cross-linked telopeptides of type II collagen (CTX-II) and cartilage oligomeric matrix protein (COMP) [1]. This study seeks to decode histological alterations in the cartilage and establish a symbiotic relationship with concentrations of specific ECM proteins within the synovial fluid as potential OA biomarkers [2,3,4].

2. Methods

Twenty-five surgically obtained cartilage tissue samples were stained with toluidine blue and analysed using the OARSI histopathological grading system under a light microscope both quantitatively and semi-quantitatively [5]. The presence of CTX-II and COMP proteins was measured in the synovial fluid samples using ELISA. The SPSS 28.0 program was used for statistical data analysis.

3. Results

The OARSI score median value was 4.0 (3.0;4.5), attributable to the delamination of the superficial cartilage zone. A greater number of single cells in comparison with cellular clusters was found: 60.00 (45.00;84.00) and 26.00 (22.00;48.00), respectively. Proteoglycan staining was 1.00 (1.00;2.00), attributable to low intensity (Figure 1). A negative correlation between ECM oedema and proteoglycan staining was found (r = −0.445; p = 0.043). The mean levels of CTX-II and COMP in synovial fluid were 1092 pg/mL (SD 537.95) and 1262 ng/mL (SD 339.47), respectively. There was a positive correlation between CTX-II and OA radiographic severity (r = 0.305; p = 0.041); the COMP and OA radiographic severity correlation was negative (r = −0.286; p = 0.049).

4. Conclusions

The identified positive correlation between OA radiographic severity and CTX-II levels in synovial fluid suggests that CTX-II may hold promise as a valuable biomarker for tracking OA progression. This implication opens up possibilities for early detection and targeted interventions in the management of the disease.

Author Contributions

Conceptualization, S.S. (Sofija Semenistaja) and S.S. (Sandra Skuja); methodology, S.S. (Sofija Semenistaja) and S.S. (Sandra Skuja); formal analysis, S.S. (Sofija Semenistaja) and L.S.; data curation, L.S., P.S., S.S. (Sofija Semenistaja); writing—original draft preparation, S.S. (Sofija Semenistaja) and S.S. (Sandra Skuja); writing—review and editing, S.S. (Sofija Semenistaja), S.S. (Sandra Skuja), A.K. and V.G. All authors have read and agreed to the published version of the manuscript.

Funding

This study received no external funding.

Institutional Review Board Statement

The study was conducted in accordance with the Declaration of Helsinki, and approved by the Ethics Committee of Rīga Stradiņš University (Decision 2-PĒK-4/36/2023 on 7 January 2023).

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study.

Data Availability Statement

A publicly available bibliographic database, PubMed.gov, was used in this study. The full bibliographic reference list is available upon request from the corresponding author.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Liu, C.; Gao, G.; Qin, X.; Deng, C.; Shen, X. Correlation Analysis of C-terminal Telopeptide of Collagen Type II and Interleukin-1β for Early Diagnosis of Knee Osteoarthritis. Orthop. Surg. 2020, 12, 286–294. [Google Scholar] [CrossRef] [PubMed]
  2. Angelini, F.; Widera, P.; Mobasheri, A.; Blair, J.; Struglics, A.; Uebelhoer, M.; Henrotin, Y.; Marijnissen, A.C.; Kloppenburg, M.; Blanco, F.J.; et al. Osteoarthritis Endotype Discovery via Clustering of Biochemical Marker Data. Ann. Rheum. Dis. 2022, 81, 666–675. [Google Scholar] [CrossRef] [PubMed]
  3. Bai, B.; Li, Y. Combined Detection of Serum CTX-II and COMP Concentrations in Osteoarthritis Model Rabbits: An Effective Technique for Early Diagnosis and Estimation of Disease Severity. J. Orthop. Surg. Res. 2016, 11, 149. [Google Scholar] [CrossRef] [PubMed]
  4. Liem, Y.; Judge, A.; Kirwan, J.; Ourradi, K.; Li, Y.; Sharif, M. Multivariable Logistic and Linear Regression Models for Identification of Clinically Useful Biomarkers for Osteoarthritis. Sci. Rep. 2020, 10, 11328. [Google Scholar] [CrossRef] [PubMed]
  5. Pritzker, K.P.H.; Gay, S.; Jimenez, S.A.; Ostergaard, K.; Pelletier, J.-P.; Revell, P.A.; Salter, D.; Van Den Berg, W.B. Osteoarthritis Cartilage Histopathology: Grading and Staging. Osteoarthr. Cartil. 2006, 14, 13–29. [Google Scholar] [CrossRef] [PubMed]
Proceedings 103 00038 g001
Figure 1. The histopathological evaluation of osteoarthritic cartilage tissue stained with toluidine blue: (A) Uneven but intact cartilage surface, occasional cellular changes, OARSI histopathological grading score 1.5; (B) Delamination of the superficial cartilage zone, vertical fissures extending into mid zone reveal some slight branching characteristic of an OARSI histopathological grading score 3.5 (white arrows); (C) Denudation of the cartilage attributable to an OARSI histopathological grading score 5.5; (D) Cartilage extracellular matrix oedema, reduced proteoglycan staining, and hypocellularity with single cells (black arrow) and rare cellular clusters visible (white arrow). Original magnification ×250, scale bars 50 µm.
Figure 1. The histopathological evaluation of osteoarthritic cartilage tissue stained with toluidine blue: (A) Uneven but intact cartilage surface, occasional cellular changes, OARSI histopathological grading score 1.5; (B) Delamination of the superficial cartilage zone, vertical fissures extending into mid zone reveal some slight branching characteristic of an OARSI histopathological grading score 3.5 (white arrows); (C) Denudation of the cartilage attributable to an OARSI histopathological grading score 5.5; (D) Cartilage extracellular matrix oedema, reduced proteoglycan staining, and hypocellularity with single cells (black arrow) and rare cellular clusters visible (white arrow). Original magnification ×250, scale bars 50 µm.
Proceedings 103 00038 g001
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MDPI and ACS Style

Semenistaja, S.; Sokolovska, L.; Studers, P.; Kadiša, A.; Groma, V.; Skuja, S. Integrating Articular Cartilage Histopathology with CTX-II and COMP as Synovial Fluid Biomarkers for a Comprehensive Analysis in Osteoarthritis Evaluation. Proceedings 2024, 103, 38. https://doi.org/10.3390/proceedings2024103038

AMA Style

Semenistaja S, Sokolovska L, Studers P, Kadiša A, Groma V, Skuja S. Integrating Articular Cartilage Histopathology with CTX-II and COMP as Synovial Fluid Biomarkers for a Comprehensive Analysis in Osteoarthritis Evaluation. Proceedings. 2024; 103(1):38. https://doi.org/10.3390/proceedings2024103038

Chicago/Turabian Style

Semenistaja, Sofija, Lība Sokolovska, Pēteris Studers, Anda Kadiša, Valērija Groma, and Sandra Skuja. 2024. "Integrating Articular Cartilage Histopathology with CTX-II and COMP as Synovial Fluid Biomarkers for a Comprehensive Analysis in Osteoarthritis Evaluation" Proceedings 103, no. 1: 38. https://doi.org/10.3390/proceedings2024103038

APA Style

Semenistaja, S., Sokolovska, L., Studers, P., Kadiša, A., Groma, V., & Skuja, S. (2024). Integrating Articular Cartilage Histopathology with CTX-II and COMP as Synovial Fluid Biomarkers for a Comprehensive Analysis in Osteoarthritis Evaluation. Proceedings, 103(1), 38. https://doi.org/10.3390/proceedings2024103038

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