Gelatin hydrogels with eicosapentaenoic acid can prevent osteoarthritis progression in vivo in a mouse model

Abstract

Eicosapentanoic acid (EPA) is an antioxidant and omega-3 polyunsaturated fatty acid that reduces inflammatory cytokine production. Gelatin hydrogel can be used as a carrier of a physiologically active substance that release it gradually for an average of similar to 3 weeks. Therefore, this study aimed to clarify the effect of EPA-incorporating gelatin hydrogels on osteoarthritis (OA) progression in vivo. Ten-week-old male C57BL/6J mice were randomly divided into six groups (n = 6): Sham, destabilization of the medial meniscus (DMM), Corn: DMM + 2 mu L corn oil, EPA injection alone (EPA-I): DMM + 2 mu L corn oil + 125 mu g/mu L EPA, Gel: DMM + gelatin hydrogels, and EPA-G: DMM + 125 mu g/mu L EPA-incorporating gelatin hydrogels. The mice were euthanized at 8 weeks after DMM or Sham surgery, and subjected to histological evaluation. Matrix-metalloproteinases-3 (MMP-3), MMP-13, interleukin-1 beta (IL-1 beta), p-IKK alpha/beta, CD86, and CD163 protein expression in the synovial cartilage was detected by immunohistochemical staining. F4/80 expression was also assessed using the F4/80 score of macrophage. Histological score was significantly lower in EPA-G than in EPA-I. MMP-3-, MMP-13-, IL-1 beta-, and p-IKK alpha/beta-positive cell ratio was significantly lower in EPA-G than in EPA-I. However, CD86- and CD163-positive cell ratio was not significantly different between EPA-I and EPA-G. The average-sum F4/80 score of macrophage in EPA-G was significantly lower than that in EPA-I. EPA-incorporating gelatin hydrogels were shown to prevent OA progression in vivo more effectively than EPA injection alone. Our results suggested that intra-articular administration of controlled-release EPA can be a new therapeutic approach for treating OA.