PMID- 32270890
OWN - NLM
STAT- MEDLINE
DCOM- 20201214
LR  - 20201214
IS  - 1554-527X (Electronic)
IS  - 0736-0266 (Linking)
VI  - 38
IP  - 10
DP  - 2020 Oct
TI  - Gelatin hydrogels with eicosapentaenoic acid can prevent osteoarthritis 
      progression in vivo in a mouse model.
PG  - 2157-2169
LID - 10.1002/jor.24688 [doi]
AB  - 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 microL corn oil, 
      EPA injection alone (EPA-I): DMM + 2 microL corn oil + 125 mug/muL EPA, Gel: 
      DMM + gelatin hydrogels, and EPA-G: DMM + 125 mug/muL 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-1beta (IL-1beta), 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-1beta-, 
      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.
CI  - (c) 2020 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.
FAU - Tsubosaka, Masanori
AU  - Tsubosaka M
AD  - Department of Orthopaedic Surgery, Kobe University School of Medicine, Kobe, 
      Japan.
FAU - Kihara, Shinsuke
AU  - Kihara S
AD  - Department of Orthopaedic Surgery, Kobe University School of Medicine, Kobe, 
      Japan.
FAU - Hayashi, Shinya
AU  - Hayashi S
AUID- ORCID: 0000-0003-4308-9845
AD  - Department of Orthopaedic Surgery, Kobe University School of Medicine, Kobe, 
      Japan.
FAU - Nagata, Junpei
AU  - Nagata J
AD  - Laboratory of Biomaterials, Institute for Frontier Life and Medical Sciences, 
      Kyoto University, Kyoto, Japan.
FAU - Kuwahara, Toshie
AU  - Kuwahara T
AD  - Laboratory of Biomaterials, Institute for Frontier Life and Medical Sciences, 
      Kyoto University, Kyoto, Japan.
FAU - Fujita, Masahiro
AU  - Fujita M
AD  - Department of Orthopaedic Surgery, Kobe University School of Medicine, Kobe, 
      Japan.
FAU - Kikuchi, Kenichi
AU  - Kikuchi K
AD  - Department of Orthopaedic Surgery, Kobe University School of Medicine, Kobe, 
      Japan.
FAU - Takashima, Yoshinori
AU  - Takashima Y
AD  - Department of Orthopaedic Surgery, Kobe University School of Medicine, Kobe, 
      Japan.
FAU - Kamenaga, Tomoyuki
AU  - Kamenaga T
AD  - Department of Orthopaedic Surgery, Kobe University School of Medicine, Kobe, 
      Japan.
FAU - Kuroda, Yuichi
AU  - Kuroda Y
AD  - Department of Orthopaedic Surgery, Kobe University School of Medicine, Kobe, 
      Japan.
FAU - Takeuchi, Kazuhiro
AU  - Takeuchi K
AD  - Department of Orthopaedic Surgery, Kobe University School of Medicine, Kobe, 
      Japan.
FAU - Fukuda, Koji
AU  - Fukuda K
AD  - Department of Orthopaedic Surgery, Kobe University School of Medicine, Kobe, 
      Japan.
FAU - Takayama, Koji
AU  - Takayama K
AD  - Department of Orthopaedic Surgery, Kobe University School of Medicine, Kobe, 
      Japan.
FAU - Hashimoto, Shingo
AU  - Hashimoto S
AD  - Department of Orthopaedic Surgery, Kobe University School of Medicine, Kobe, 
      Japan.
FAU - Matsumoto, Tomoyuki
AU  - Matsumoto T
AD  - Department of Orthopaedic Surgery, Kobe University School of Medicine, Kobe, 
      Japan.
FAU - Niikura, Takahiro
AU  - Niikura T
AD  - Department of Orthopaedic Surgery, Kobe University School of Medicine, Kobe, 
      Japan.
FAU - Tabata, Yasuhiko
AU  - Tabata Y
AD  - Laboratory of Biomaterials, Institute for Frontier Life and Medical Sciences, 
      Kyoto University, Kyoto, Japan.
FAU - Kuroda, Ryosuke
AU  - Kuroda R
AD  - Department of Orthopaedic Surgery, Kobe University School of Medicine, Kobe, 
      Japan.
LA  - eng
PT  - Journal Article
DEP - 20200415
PL  - United States
TA  - J Orthop Res
JT  - Journal of orthopaedic research : official publication of the Orthopaedic 
      Research Society
JID - 8404726
RN  - 0 (Biomarkers)
RN  - 0 (Hydrogels)
RN  - 0 (Micelles)
RN  - 9000-70-8 (Gelatin)
RN  - AAN7QOV9EA (Eicosapentaenoic Acid)
SB  - IM
MH  - Animals
MH  - Biomarkers/metabolism
MH  - Cartilage, Articular/metabolism
MH  - Disease Progression
MH  - Drug Evaluation, Preclinical
MH  - Eicosapentaenoic Acid/*administration & dosage
MH  - Gelatin
MH  - Humans
MH  - Hydrogels
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Micelles
MH  - Osteoarthritis/*drug therapy/metabolism
MH  - Primary Cell Culture
MH  - Random Allocation
MH  - Synovitis/drug therapy
OTO - NOTNLM
OT  - eicosapentaenoic acid
OT  - gelatin hydrogel
OT  - omega-3 polyunsaturated fatty acid
OT  - osteoarthritis
EDAT- 2020/04/10 06:00
MHDA- 2020/12/15 06:00
CRDT- 2020/04/10 06:00
PHST- 2020/02/07 00:00 [received]
PHST- 2020/04/05 00:00 [revised]
PHST- 2020/04/06 00:00 [accepted]
PHST- 2020/04/10 06:00 [pubmed]
PHST- 2020/12/15 06:00 [medline]
PHST- 2020/04/10 06:00 [entrez]
AID - 10.1002/jor.24688 [doi]
PST - ppublish
SO  - J Orthop Res. 2020 Oct;38(10):2157-2169. doi: 10.1002/jor.24688. Epub 2020 Apr 
      15.