PMID- 31876323
OWN - NLM
STAT- MEDLINE
DCOM- 20201119
LR  - 20201119
IS  - 1095-8355 (Electronic)
IS  - 1065-6995 (Linking)
VI  - 44
IP  - 4
DP  - 2020 Apr
TI  - Protective effects of cilengitide on inflammation in chondrocytes under excessive 
      mechanical stress.
PG  - 966-974
LID - 10.1002/cbin.11293 [doi]
AB  - Chondrocytes constantly receive external stimuli, which regulates remodeling. An 
      optimal level of mechanical stress is essential for maintaining chondrocyte 
      homeostasis, however, excessive mechanical stress induces inflammatory cytokines 
      and protease, such as matrix metalloproteinases (MMPs). Therefore, excessive 
      mechanical stress is considered to be one of the main causes to cartilage 
      destruction leading to osteoarthritis (OA). Integrins are well-known as cell 
      adhesion molecules and act as receptors for extracellular matrix (ECM), and are 
      believed to control intracellular signaling pathways both physically and 
      chemically as a mechanoreceptor. However, few studies have focused on the roles 
      and functions of integrins in inflammation caused by excessive mechanical stress. 
      In this study, we examined the relationship between integrins (alphaVbeta3 and alphaVbeta5) and 
      the expression of inflammatory factors under mechanical loading in chondrocytes 
      by using an integrin receptor antagonist (cilengitide). Cilengitide suppressed 
      the gene expression of interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), 
      matrix metalloproteinase-3 (MMP-3), and MMP-13 induced by excessive mechanical 
      stress. In addition, the protein expression of IL1-beta and MMP-13 was also 
      inhibited by the addition of cilengitide. Next, we investigated the involvement 
      of intracellular signaling pathways in stress-induced integrin signaling in 
      chondrocytes by using western blotting. The levels of p-FAK, p-ERK, p-JNK, and 
      p-p38 were enhanced by excessive mechanical stress and the enhancement was 
      suppressed by treatment with cilengitide. In conclusion, this study revealed that 
      excessive mechanical stress may activate integrins alphaVbeta3 and alphaVbeta5 on the surface 
      of chondrocytes and thereby induce an inflammatory reaction by upregulating the 
      expression of IL-1beta, TNF-alpha, MMP-3, and MMP-13 through phosphorylation of FAK and 
      MAPKs.
CI  - (c) 2019 International Federation for Cell Biology.
FAU - Hirose, Naoto
AU  - Hirose N
AUID- ORCID: 0000-0003-3354-6694
AD  - Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima 
      University Graduate School of Biomedical and Health Sciences, Kasumi 1-2-3 
      Minami-ku, Hiroshima-shi, Hiroshima prefecture, 7348551, Japan.
FAU - Okamoto, Yuki
AU  - Okamoto Y
AD  - Department of Orthodontics, Division of Oral Health and Development, Hiroshima 
      University Hospital, Hiroshima, Japan.
FAU - Yanoshita, Makoto
AU  - Yanoshita M
AD  - Department of Orthodontics, Division of Oral Health and Development, Hiroshima 
      University Hospital, Hiroshima, Japan.
FAU - Asakawa, Yuki
AU  - Asakawa Y
AD  - Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima 
      University Graduate School of Biomedical and Health Sciences, Kasumi 1-2-3 
      Minami-ku, Hiroshima-shi, Hiroshima prefecture, 7348551, Japan.
FAU - Sumi, Chikako
AU  - Sumi C
AD  - Department of Orthodontics, Division of Oral Health and Development, Hiroshima 
      University Hospital, Hiroshima, Japan.
FAU - Takano, Mami
AU  - Takano M
AD  - Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima 
      University Graduate School of Biomedical and Health Sciences, Kasumi 1-2-3 
      Minami-ku, Hiroshima-shi, Hiroshima prefecture, 7348551, Japan.
FAU - Nishiyama, Sayuri
AU  - Nishiyama S
AD  - Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima 
      University Graduate School of Biomedical and Health Sciences, Kasumi 1-2-3 
      Minami-ku, Hiroshima-shi, Hiroshima prefecture, 7348551, Japan.
FAU - Su, Shao-Ching
AU  - Su SC
AD  - Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima 
      University Graduate School of Biomedical and Health Sciences, Kasumi 1-2-3 
      Minami-ku, Hiroshima-shi, Hiroshima prefecture, 7348551, Japan.
FAU - Mitsuyoshi, Tomomi
AU  - Mitsuyoshi T
AD  - Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima 
      University Graduate School of Biomedical and Health Sciences, Kasumi 1-2-3 
      Minami-ku, Hiroshima-shi, Hiroshima prefecture, 7348551, Japan.
FAU - Kunimatsu, Ryo
AU  - Kunimatsu R
AD  - Department of Orthodontics, Division of Oral Health and Development, Hiroshima 
      University Hospital, Hiroshima, Japan.
FAU - Tanne, Kazuo
AU  - Tanne K
AD  - Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima 
      University Graduate School of Biomedical and Health Sciences, Kasumi 1-2-3 
      Minami-ku, Hiroshima-shi, Hiroshima prefecture, 7348551, Japan.
FAU - Tanimoto, Kotaro
AU  - Tanimoto K
AD  - Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima 
      University Graduate School of Biomedical and Health Sciences, Kasumi 1-2-3 
      Minami-ku, Hiroshima-shi, Hiroshima prefecture, 7348551, Japan.
LA  - eng
GR  - Grants-in-Aid 26861788/Scientific Research of Japan Society/
PT  - Journal Article
DEP - 20200106
PL  - England
TA  - Cell Biol Int
JT  - Cell biology international
JID - 9307129
RN  - 0 (Cytokines)
RN  - 0 (Integrin alphaVbeta3)
RN  - 0 (Receptors, Vitronectin)
RN  - 0 (Snake Venoms)
RN  - 0 (integrin alphaVbeta5)
RN  - 4EDF46E4GI (Cilengitide)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Chondrocytes/*metabolism/pathology
MH  - Cytokines/metabolism
MH  - Integrin alphaVbeta3/*metabolism
MH  - Mice
MH  - Osteoarthritis/*metabolism
MH  - Receptors, Vitronectin/*metabolism
MH  - Snake Venoms/*pharmacology
MH  - *Stress, Mechanical
OTO - NOTNLM
OT  - chondrocyte
OT  - cilengitide
OT  - inflammation
OT  - integrins alphaVbeta3 and alphaVbeta5
OT  - mechanical stress
EDAT- 2019/12/27 06:00
MHDA- 2020/11/20 06:00
CRDT- 2019/12/27 06:00
PHST- 2019/07/04 00:00 [received]
PHST- 2019/12/21 00:00 [accepted]
PHST- 2019/12/27 06:00 [pubmed]
PHST- 2020/11/20 06:00 [medline]
PHST- 2019/12/27 06:00 [entrez]
AID - 10.1002/cbin.11293 [doi]
PST - ppublish
SO  - Cell Biol Int. 2020 Apr;44(4):966-974. doi: 10.1002/cbin.11293. Epub 2020 Jan 6.