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 ~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 µL corn oil, EPA injection alone (EPA-I): DMM + 2 µL corn oil + 125 μg/μL EPA, Gel: DMM + gelatin hydrogels, and EPA-G: DMM + 125 μg/μL 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-1β (IL-1β), p-IKK α/β, 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-1β-, and p-IKK α/β-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.
Highlights
Eicosapentaenoic acid (EPA) is an antioxidant and a type of n-3 polyunsaturated fatty acid (PUFA) contained in fish oil [1]
Our results suggested that intra-articular administration of controlled-release Eicosapentanoic acid (EPA) can be a new therapeutic approach for treating OA
Regarding OA, we previously reported that EPA treatment inhibits chondrocyte apoptosis and MMP expression induced by oxidative stress in vitro, and prevents OA progression in vivo [7]
Summary
Eicosapentaenoic acid (EPA) is an antioxidant and a type of n-3 polyunsaturated fatty acid (PUFA) contained in fish oil [1]. Another study reported that a combination of BMP-2releasing gelatin/β-TCP sponge is a promising technique to induce bone regeneration in bone marrow for treating segmental bone defects induced by X-ray irradiation [13]. These findings on the antioxidant action of EPA and the applicability effect of gelatin hydrogels as an innovative drug delivery system suggested that gelatin hydrogels containing EPA might have be more effective than EPA alone in preventing OA progression. This study aimed to investigate the effect of gelatin hydrogels containing EPA on OA progression in vivo. This study aimed to investigate the effect of EPA-incorporating gelatin hydrogels on osteoarthritis (OA) progression in vivo
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