PMID- 31560698
OWN - NLM
STAT- MEDLINE
DCOM- 20200312
LR  - 20210630
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 14
IP  - 9
DP  - 2019
TI  - HMGB1 mediates the development of tendinopathy due to mechanical overloading.
PG  - e0222369
LID - 10.1371/journal.pone.0222369 [doi]
LID - e0222369
AB  - Mechanical overloading is a major cause of tendinopathy, but the underlying 
      pathogenesis of tendinopathy is unclear. Here we report that high mobility group 
      box1 (HMGB1) is released to the tendon extracellular matrix and initiates an 
      inflammatory cascade in response to mechanical overloading in a mouse model. 
      Moreover, administration of glycyrrhizin (GL), a naturally occurring triterpene 
      and a specific inhibitor of HMGB1, inhibits the tendon's inflammatory reactions. 
      Also, while prolonged mechanical overloading in the form of long-term intensive 
      treadmill running induces Achilles tendinopathy in mice, administration of GL 
      completely blocks the tendinopathy development. Additionally, mechanical 
      overloading of tendon cells in vitro induces HMGB1 release to the extracellular 
      milieu, thereby eliciting inflammatory and catabolic responses as marked by 
      increased production of prostaglandin E2 (PGE2) and matrix metalloproteinase-3 
      (MMP-3) in tendon cells. Application of GL abolishes the cellular 
      inflammatory/catabolic responses. Collectively, these findings point to HMGB1 as 
      a key molecule that is responsible for the induction of tendinopathy due to 
      mechanical overloading placed on the tendon.
FAU - Zhao, Guangyi
AU  - Zhao G
AD  - MechanoBiology Laboratory, Department of Orthopaedic Surgery, University of 
      Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
FAU - Zhang, Jianying
AU  - Zhang J
AD  - MechanoBiology Laboratory, Department of Orthopaedic Surgery, University of 
      Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
FAU - Nie, Daibang
AU  - Nie D
AD  - MechanoBiology Laboratory, Department of Orthopaedic Surgery, University of 
      Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
AD  - Department of Immunology, College of Basic Medicine, Chongqing Medical 
      University, Chongqing, China.
FAU - Zhou, Yiqin
AU  - Zhou Y
AD  - MechanoBiology Laboratory, Department of Orthopaedic Surgery, University of 
      Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
AD  - Joint Surgery and Sports Medicine Department, Shanghai Changzheng Hospital, 
      Second Military Medical University, Huangpu, Shanghai, China.
FAU - Li, Feng
AU  - Li F
AD  - MechanoBiology Laboratory, Department of Orthopaedic Surgery, University of 
      Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
FAU - Onishi, Kentaro
AU  - Onishi K
AD  - Department of Physical Medicine and Rehabilitation, University of Pittsburgh, 
      Pittsburgh, Pennsylvania, United States of America.
FAU - Billiar, Timothy
AU  - Billiar T
AD  - Department of Surgery, University of Pittsburgh, Pennsylvania, United States of 
      America.
FAU - Wang, James H-C
AU  - Wang JH
AUID- ORCID: 0000-0001-7279-0679
AD  - MechanoBiology Laboratory, Department of Orthopaedic Surgery, University of 
      Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
AD  - Department of Physical Medicine and Rehabilitation, University of Pittsburgh, 
      Pittsburgh, Pennsylvania, United States of America.
AD  - Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, 
      United States of America.
LA  - eng
GR  - P30 AG024827/AG/NIA NIH HHS/United States
GR  - R21 AR070340/AR/NIAMS NIH HHS/United States
GR  - P30 DK120531/DK/NIDDK NIH HHS/United States
GR  - R01 AR065949/AR/NIAMS NIH HHS/United States
GR  - R01 AR061395/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20190927
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (HMGB1 Protein)
RN  - 0 (HMGB1 protein, mouse)
RN  - 6FO62043WK (Glycyrrhizic Acid)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - K7Q1JQR04M (Dinoprostone)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Dinoprostone/metabolism
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Glycyrrhizic Acid/pharmacology
MH  - HMGB1 Protein/antagonists & inhibitors/metabolism/*physiology
MH  - Matrix Metalloproteinase 3/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Rats, Sprague-Dawley
MH  - Tendinopathy/etiology/*metabolism/physiopathology
MH  - Tendons/cytology/metabolism/physiopathology
MH  - Weight-Bearing/physiology
PMC - PMC6764662
COIS- The authors have declared that no competing interests exist.
EDAT- 2019/09/29 06:00
MHDA- 2020/03/13 06:00
PMCR- 2019/09/27
CRDT- 2019/09/28 06:00
PHST- 2019/08/21 00:00 [received]
PHST- 2019/09/16 00:00 [accepted]
PHST- 2019/09/28 06:00 [entrez]
PHST- 2019/09/29 06:00 [pubmed]
PHST- 2020/03/13 06:00 [medline]
PHST- 2019/09/27 00:00 [pmc-release]
AID - PONE-D-19-23610 [pii]
AID - 10.1371/journal.pone.0222369 [doi]
PST - epublish
SO  - PLoS One. 2019 Sep 27;14(9):e0222369. doi: 10.1371/journal.pone.0222369. 
      eCollection 2019.