PMID- 29534523
OWN - NLM
STAT- MEDLINE
DCOM- 20180905
LR  - 20181114
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 19
IP  - 3
DP  - 2018 Mar 12
TI  - Exploring the In Vivo Anti-Inflammatory Actions of Simvastatin-Loaded Porous 
      Microspheres on Inflamed Tenocytes in a Collagenase-Induced Animal Model of 
      Achilles Tendinitis.
LID - 10.3390/ijms19030820 [doi]
LID - 820
AB  - Tendon rupture induces an inflammatory response characterized by release of 
      pro-inflammatory cytokines and impaired tendon performance. This study sought to 
      investigate the therapeutic effects of simvastatin-loaded porous microspheres 
      (SIM/PMSs) on inflamed tenocytes in vitro and collagenase-induced Achilles 
      tendinitis in vivo. The treatment of SIM/PMSs in lipopolysaccharide (LPS)-treated 
      tenocytes reduced the mRNA expressions of pro-inflammatory cytokines (Matrix 
      metalloproteinase-3 (MMP-3), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), and 
      tumor necrosis factor-alpha (TNF-alpha)). In addition, the local injection of SIM/PMSs 
      into the tendons of collagenase-induced Achilles tendinitis rat models suppressed 
      pro-inflammatory cytokines (MMP-3, COX-2, IL-6, TNF-alpha, and MMP-13). This local 
      treatment also upregulated anti-inflammatory cytokines (IL-4, IL-10, and IL-13). 
      Furthermore, treatment with SIM/PMSs also improved the alignment of collagen 
      fibrils and effectively prevented collagen disruption in a dose-dependent manner. 
      Therefore, SIM/PMSs treatment resulted in an incremental increase in the collagen 
      content, stiffness, and tensile strength in tendons. This study suggests that 
      SIM/PMSs have great potential for tendon healing and restoration in Achilles 
      tendinitis.
FAU - Jeong, Chandong
AU  - Jeong C
AD  - Department of Orthopedic Surgery and Rare Diseases Institute, Korea University 
      College of Medicine, Guro Hospital, Guro-dong, Guro-gu, Seoul 08308, Korea. 
      cdjeong85@gmail.com.
AD  - Department of Biomedical Science, Korea University College of Medicine, 
      Anam-dong, Seongbuk-gu, Seoul 02841, Korea. cdjeong85@gmail.com.
FAU - Kim, Sung Eun
AU  - Kim SE
AD  - Department of Orthopedic Surgery and Rare Diseases Institute, Korea University 
      College of Medicine, Guro Hospital, Guro-dong, Guro-gu, Seoul 08308, Korea. 
      sekim10@korea.ac.kr.
FAU - Shim, Kyu-Sik
AU  - Shim KS
AD  - Department of Biomedical Science, Korea University College of Medicine, 
      Anam-dong, Seongbuk-gu, Seoul 02841, Korea. breakdown88@nate.com.
FAU - Kim, Hak-Jun
AU  - Kim HJ
AD  - Department of Orthopedic Surgery and Rare Diseases Institute, Korea University 
      College of Medicine, Guro Hospital, Guro-dong, Guro-gu, Seoul 08308, Korea. 
      dakjul@korea.ac.kr.
FAU - Song, Mi Hyun
AU  - Song MH
AD  - Department of Orthopedic Surgery and Rare Diseases Institute, Korea University 
      College of Medicine, Guro Hospital, Guro-dong, Guro-gu, Seoul 08308, Korea. 
      wwiiw@naver.com.
FAU - Park, Kyeongsoon
AU  - Park K
AUID- ORCID: 0000-0003-3625-4128
AD  - Department of Systems Biotechnology, Chung-Ang University, Anseong, Gyeonggi-do 
      17546, Korea. kspark1223@cau.ac.kr.
FAU - Song, Hae-Ryong
AU  - Song HR
AD  - Department of Orthopedic Surgery and Rare Diseases Institute, Korea University 
      College of Medicine, Guro Hospital, Guro-dong, Guro-gu, Seoul 08308, Korea. 
      songhae@korea.ac.kr.
LA  - eng
PT  - Journal Article
DEP - 20180312
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Interleukins)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 9007-34-5 (Collagen)
RN  - AGG2FN16EV (Simvastatin)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 3.4.24.- (Collagenases)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
SB  - IM
MH  - Achilles Tendon/pathology
MH  - Animals
MH  - Anti-Inflammatory Agents/administration & dosage/*pharmacology
MH  - Cells, Cultured
MH  - Collagen/genetics/metabolism
MH  - Collagenases/toxicity
MH  - Cyclooxygenase 2/genetics/metabolism
MH  - Interleukins/genetics/metabolism
MH  - Lipopolysaccharides/toxicity
MH  - Matrix Metalloproteinases/genetics/metabolism
MH  - *Microspheres
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Simvastatin/administration & dosage/*pharmacology
MH  - Tendinopathy/*drug therapy/etiology
MH  - Tenocytes/*drug effects/metabolism
MH  - Tumor Necrosis Factor-alpha/genetics/metabolism
PMC - PMC5877681
OTO - NOTNLM
OT  - Achilles tendinitis
OT  - anti-inflammation
OT  - porous microspheres
OT  - simvastatin
OT  - tendon healing
COIS- The authors declare no conflict of interest.
EDAT- 2018/03/15 06:00
MHDA- 2018/09/06 06:00
PMCR- 2018/03/01
CRDT- 2018/03/15 06:00
PHST- 2018/01/18 00:00 [received]
PHST- 2018/02/25 00:00 [revised]
PHST- 2018/03/08 00:00 [accepted]
PHST- 2018/03/15 06:00 [entrez]
PHST- 2018/03/15 06:00 [pubmed]
PHST- 2018/09/06 06:00 [medline]
PHST- 2018/03/01 00:00 [pmc-release]
AID - ijms19030820 [pii]
AID - ijms-19-00820 [pii]
AID - 10.3390/ijms19030820 [doi]
PST - epublish
SO  - Int J Mol Sci. 2018 Mar 12;19(3):820. doi: 10.3390/ijms19030820.