A Porcine Animal Model for Early Meniscal Degeneration – Analysis of Histology, Gene Expression and Magnetic Resonance Imaging Six Months after Resection of the Anterior Cruciate Ligament

Abstract

Background/ObjectiveThe menisci of the mammalian knee joint balance the incongruence between femoral condyle and tibial plateau and thus menisci absorb and distribute high loads. Degeneration processes of the menisci lead to pain syndromes in the knee joint. The origin of such degenerative processes on meniscal tissue is rarely understood and may be described best as an imbalance of anabolic and catabolic metabolism. A standardized animal model of meniscal degeneration is needed for further studies. The aim of the current study was to develop a porcine animal model with early meniscal degeneration.Material and MethodsResection of the anterior cruciate ligament (ACLR) was performed on the left knee joints of eight Göttingen minipigs. A sham operation was carried out on the right knee joint. The grade of degeneration was determined 26 weeks after the operation using histology and magnetic resonance imaging (MRI). Furthermore, the expression of 14 genes which code for extracellular matrix proteins, catabolic matrix metalloproteinases and inflammation mediators were analyzed.ResultsDegenerative changes were detected by a histological analysis of the medial meniscus after ACLR. These changes were not detected by MRI. In terms of their gene expression profile, these degenerated medial menisci showed a significantly increased expression of COL1A1.ConclusionThis paper describes a new animal model for early secondary meniscal degeneration in the Göttingen minipig. Histopathological evidence of the degenerative changes could be described. This early degenerative changes could not be seen by NMR imaging.

Osteoarthritis in the Knee Joints of Göttingen Minipigs after Resection of the Anterior Cruciate Ligament? Missing Correlation of MRI, Gene and Protein Expression with Histological Scoring

“…Kreinest et al [45] report similar findings, as degenerative changes of the menisci were not detected by MRI also in the same animals as we assessed in the present study.…”

“…However, col1a1 was upregulated in the menisci of the animals used in the presented study which was identified as degeneration of the meniscal tissue [45]; Thus a change in the assessed articular cartilage should have been detected. For other genes, for example acan , our findings were shared with some authors but differed from the findings of others [12,18,21,41,125,127,128,129].…”

“…Sample size calculation was done for the study regarding changes in the menisci in the stifle joints, which is described elsewhere [45]. …”

Platelet-Rich Fibrin Facilitates Rabbit Meniscal Repair by Promoting Meniscocytes Proliferation, Migration, and Extracellular Matrix Synthesis

“…The pathologist was blinded to the treatment groups. All samples were semi-quantitatively graded using a four-stage meniscus score based on the HE-staining [ 49 ]. Major criteria listed in Table 1 .…”

Clinical magnetic resonance-enabled characterization of mono-iodoacetate-induced osteoarthritis in a large animal species

“…While dogs have many properties favorable for use in OA models, interest in replacing companion animals with use species (in the research setting) has led to the development of knee OA models using swine, which offer a similarly faithful anatomical representation of the human knee[ 22 – 28 ]. However, existing swine models suffer from some critical shortcomings that limit their utility especially when quantitative results are desired as outcome parameters such as grading the benefit of a (hypothetical) new OA treatment[ 23 , 27 ]. An ideal large animal knee OA model should i) allow for efficient induction of the pathology such as by a simple intraarticular injection, ii) rely only on a widely available, well-standardized use animal species such as swine, iii) allow the induction of several states of severity (such as “mild,” “moderate,” and “severe”), and, most importantly, iv) provide an in vivo method for the quantification of OA knee damage that allows for serial assessment in the course of a study without necessitating the sacrifice of test subjects at (inefficiently) early time points.…”