Abstract
BackgroundAnimal model of Knee Osteoarthritis (OA) is the primary testing methodology for studies on pathogenic mechanisms and therapies of human OA disease. Recent major modeling methods are divided into artificially induced and spontaneous. However, these methods have some disadvantages of slow progression, high cost and no correlation with the pathogenesis of OA.MethodsOur studies attempted to find a rapid, easy, and consistent with the natural pathological process of OA modeling method by intra-articular injection of stromal cell-derived factor 1 (SDF-1) in the rabbit knee. After induction we collected cartilage specimens from the medial femoral condyle to undergo macroscopic, histological, immunohistochemical, and biochemical evaluations. Meanwhile, compared with Hulth surgical method to evaluate its efficacy.ResultsMacroscopic observation and modified Mankin score of histological staining exhibited typical features of middle stage OA cartilage in SDF-1 injected groups. Immunohistochemically, the positive expression of interleukin-1 (IL-1) and tumor necrosis factor α(TNF-α) was earlier and higher in high dose SDF-1 group than the surgical group. The matrix metalloproteinases (MMPs) in synovial fluid and chondrocytes significantly increased, but type II collagen (COLII) and aggrecan (ACAN) protein expressions decreased in SDF-1 injected group following the extension of time and increase of SDF-1 concentration.ConclusionsOur data indicated intra-articular injection of SDF-1 (40μg/kg, three times for 12 weeks) can induce rabbit knee OA model successfully more rapidly and easily than traditional surgical modeling. The study provided a further option for the establishment of knee OA animal model.
Highlights
Animal model of Knee Osteoarthritis (OA) is the primary testing methodology for studies on pathogenic mechanisms and therapies of human OA disease
After 8 weeks, the cartilage surface of medial femoral condyles in the experimental groups showed roughness and dry, the gloss dulling, and even some cartilage defections appeared in stromal cell-derived factor 1 (SDF-1) 40μg/kg group and the surgical group compare with the blank group (Fig. 1f–j)
The severity of cartilage degeneration demonstrates in a dosage dependent manner in various concentrations of SDF-1 injected groups, and SDF-1 40μg/kg group was similar to the surgical group
Summary
Animal model of Knee Osteoarthritis (OA) is the primary testing methodology for studies on pathogenic mechanisms and therapies of human OA disease. Recent major modeling methods are divided into artificially induced and spontaneous. These methods have some disadvantages of slow progression, high cost and no correlation with the pathogenesis of OA. Animal models research is an important method to study OA pathology, including artificially induced and spontaneous models. Artificially induced modeling has a rapid progression, including biochemical or surgical induction. Biochemical modeling method, intraarticular injection chemicals such as papain and collagenase, shows high results in relatively homogeneous degree and reproducibility of a pathological state in a short period. The method exists controversy about the pathophysiology, which biochemical model might induce significant amount of inflammation and may not represent naturally occurring OA state found in human [8]
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