Artikel
Osteoarthritis in the knee joints of Göttingen Minipigs whether after resection of the anterior cruciate ligament or not. Missing correlation of MRI, gene or protein expression with histological scoring
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Autoren
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Gregor Reisig
- Medical Faculty Mannheim, University of Heidelberg, Orthopaedic and Trauma Surgery Centre (OUZ), Department for experimental Orthopaedics and Trauma Surgery, Mannheim, Germany
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Michael Kreinest
- Medical Faculty Mannheim, University of Heidelberg, Orthopaedic and Trauma Surgery Centre (OUZ), Department for experimental Orthopaedics and Trauma Surgery, Mannheim, Germany
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Wiltrud Richter
- Research Centre for Experimental Orthopaedics, Heidelberg University Hospital, Heidelberg, Germany
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Dietmar Dinter
- Radiology Schwetzingen, Schwetzingen, Germany
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Ulrike Attenberger
- University Medical Center Mannheim, Institute of Clinical Radiology and Nuclear Medicine, Mannheim, Germany
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Joachim Brade
- Medical Faculty Mannheim University of Heidelberg, Department of Medical Statistics and Biomathematics, Mannheim, Germany
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Mechthild Wagner-Ecker
- Research Centre for Experimental Orthopaedics, Heidelberg University Hospital, Heidelberg, Germany
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Markus Schwarz
- Medical Faculty Mannheim, University of Heidelberg, Orthopaedic and Trauma Surgery Centre (OUZ), Department for experimental Orthopaedics and Trauma Surgery, Mannheim, Germany
| Veröffentlicht: | 5. Oktober 2015 |
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Gliederung
Text
Objectives: The Göttingen Minipig (GM) serves as large animal model in articular cartilage research. The aim of the study was to induce osteoarthritis (OA) in GM by the resection of the anterior cruciate ligament (ACLR) according to Pond and Nuki [1], verified by histological and MRI scoring as well as analysis of gene and protein expression.
Methods: The study was approved by the regional ethical committee. 8 female GM (>24 month, 45-55 kg) underwent ACLR in the left knees, the right knees served as controls (sham operation). After 26 weeks, the knee joints were examined via magnetic resonance imaging (MRI) under anaesthesia. A 3-Tesla high-field MR tomography unit (Magnetom Trio, Siemens, Erlangen, Germany) with a 3 T CP Large Flex Coil (Siemens, Erlangen, Germany) and standard proton-density weighted fat saturated sequences in coronal and sagittal direction (slice thickness 3 mm with 10% gap) were used. Histological samples (4 mm Ø) were taken from either the most degenerated area or -if no degeneration was visible- the main loading zone of the med./lat. tibia plateau and med./lat. condyles respectively. Adjacent surrounding cartilage (10mm Ø) was used for gene expression analysis. After literature search 10 genes (ADAMTS4, ADAMTS5, ACAN, COL1A1, COL2, IL1B, MMP1, MMP3, MMP13, VEGF) were analysed by qRT-PCR with ß-actin as reference in doublettes for their expression patterns. Also, immunohistochemical staining (IH) of Col I and II was performed. MRI scans were assessed by 2 blinded radiologists according to a modified WORMS-score [2]. Histological sections (HE and safranin-o staining) were scored by 3 blinded experts according to Little et al. [3]. IH was scored using a 4 point grading, with no (0) to intense (3) staining. Statistical calculations were made by SAS 9.3 (SAS, Heidelberg, Germany) and Excel 2010 (MS Corp., Redmond WA, US).
Results and Conclusion: OA was seen in histological specimens originating from both knee joints without difference between the ACLR and sham site (left: 6.48 ± 5.58; right: 6.86 ± 5.75; p= 0.7953, t-test). The MRI scoring was 0.34 ± 0.89 (left) and 0.03 ± 0.17 (right) without correlation between the histological and MRI scores (r=0.10021). OA changes were not always able to be detected by the MRI imaging.
Histological findings showed no correlation with the heterogeneous gene expression and IH findings.
OA changes emerged in the knee joints of GM older than 2 years but we were not able to distinguish if the OA was spontaneous or induced by the ACLR. The used MRI technique was obviously not adequate to diagnose OA.
References
- 1.
- Pond MJ, Nuki G. Experimentally-induced osteoarthritis in the dog. Ann Rheum Dis. 1973;32:387-388.
- 2.
- Peterfy, et al. Whole-Organ Magnetic Resonance Imaging Score (WORMS) of the knee in osteoarthritis. Osteoarthritis Cartilage. 2004;12:177-190.
- 3.
- Little, et al. The OARSI histopathology initiative - recommendations for histological assessments of osteoarthritis in sheep and goats. Osteoarthritis Cartilage. 2010;18 Suppl 3:S80-92.
