Gelatin hydrogels with eicosapentaenoic acid can prevent osteoarthritis progression in vivo in a mouse model
Tsubosaka M, Kihara S, Hayashi S, Nagata J, Kuwahara T, Fujita M, Kikuchi K, Takashima Y, Kamenaga T, Kuroda Y, Takeuchi K, Fukuda K, Takayama K, Hashimoto S, Matsumoto T, Niikura T, Tabata Y, Kuroda R
Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 22 citations
How it was studied
- Design
- Animal study (classified by our AI screen)
- Studied in
- Animals
- Main outcome
- Health markers and function
Who paid for it
- Funding
- Independent funding
- Government
- Japan Society for the Promotion of Science
- Grants
- Japan Society for the Promotion of Science (18K09105); Japan Society for the Promotion of Science (20K09147)
Based on 1 listed funder(s).
Publication
- Published
- 2020-04-09 · J Orthop Res · vol. 38 · issue 10 · pp. 2157–2169
- Publisher
- Wiley
- Cited
- 31 citations · more than 89% of similar papers · 2.4× the field average
- References
- 42 works
- Access
- Open access (repository copy)
- Research areas
- Osteoarthritis Treatment and Mechanisms · Inflammatory mediators and NSAID effects · Veterinary Equine Medical Research
- Keywords
- Eicosapentaenoic acid, Gelatin, Self-healing hydrogels, Chemistry, In vivo, Corn oil, Osteoarthritis, Polyunsaturated fatty acid, Hyaluronic acid, Pharmacology, Medicine, Fatty acid, Biochemistry, Pathology, Food science, Biology, Biotechnology, Anatomy
- MeSH
- cartilage, articular, animals, mice, inbred c57bl, humans, osteoarthritis, synovitis, disease progression, eicosapentaenoic acid, gelatin, hydrogels, random allocation, drug evaluation, preclinical, micelles, male, primary cell culture, biomarkers
18 authors
From JP
- Masanori TsubosakaKobe University
- Shinsuke KiharaKobe University
- Shinya Hayashi · correspondingKobe University
- Junpei NagataKyoto University
- Toshie KuwaharaKyoto University
- Masahiro FujitaKobe University
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.
Abstract via Europe PMC. Copyright remains with the authors or publisher.
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