PMID- 29891998
OWN - NLM
STAT- MEDLINE
DCOM- 20191010
LR  - 20191010
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 8
IP  - 1
DP  - 2018 Jun 11
TI  - Association of Inflammatory Responses and ECM Disorganization with HMGB1 
      Upregulation and NLRP3 Inflammasome Activation in the Injured Rotator Cuff 
      Tendon.
PG  - 8918
LID - 10.1038/s41598-018-27250-2 [doi]
LID - 8918
AB  - Inflammation and extracellular matrix (ECM) disorganization following the rotator 
      cuff tendon injuries (RCTI) delay the repair and healing process and the 
      molecular mechanisms underlying RCTI pathology are largely unknown. Here, we 
      examined the role of HMGB1 and NLRP3 inflammasome pathway in the inflammation and 
      ECM disorganization in RCTI. This hypothesis was tested in a tenotomy-RCTI rat 
      model by transecting the RC tendon from the humerus. H&E and pentachrome staining 
      revealed significant changes in the morphology, architecture and ECM organization 
      in RC tendon tissues following RCTI when compared with contralateral control. 
      Severity of the injury was high in the first two weeks with improvement in 3-4 
      weeks following RCTI, and this correlated with the healing response. The 
      expression of proteins associated with increased HMGB-1 and upregulation of NLRP3 
      inflammasome pathway, TLR4, TLR2, TREM-1, RAGE, ASC, Caspase-1, and IL-1beta, in the 
      first two weeks following RCTI followed by decline in 3-4 weeks. These results 
      suggest the association of inflammatory responses and ECM disorganization with 
      HMGB1 upregulation and NLRP3 inflammasome activation in the RC tendons and could 
      provide novel target(s) for development of better therapeutic strategies in the 
      management of RCTI.
FAU - Thankam, Finosh G
AU  - Thankam FG
AD  - Departments of Clinical & Translational Science and Orthopedic Surgery, Creighton 
      University School of Medicine, Omaha, NE, 68178, USA.
FAU - Roesch, Zachary K
AU  - Roesch ZK
AD  - Departments of Clinical & Translational Science and Orthopedic Surgery, Creighton 
      University School of Medicine, Omaha, NE, 68178, USA.
FAU - Dilisio, Matthew F
AU  - Dilisio MF
AD  - Departments of Clinical & Translational Science and Orthopedic Surgery, Creighton 
      University School of Medicine, Omaha, NE, 68178, USA.
FAU - Radwan, Mohamed M
AU  - Radwan MM
AD  - Departments of Clinical & Translational Science and Orthopedic Surgery, Creighton 
      University School of Medicine, Omaha, NE, 68178, USA.
FAU - Kovilam, Anuradha
AU  - Kovilam A
AD  - Departments of Clinical & Translational Science and Orthopedic Surgery, Creighton 
      University School of Medicine, Omaha, NE, 68178, USA.
FAU - Gross, R Michael
AU  - Gross RM
AD  - Departments of Clinical & Translational Science and Orthopedic Surgery, Creighton 
      University School of Medicine, Omaha, NE, 68178, USA.
FAU - Agrawal, Devendra K
AU  - Agrawal DK
AUID- ORCID: 0000-0001-5445-0013
AD  - Departments of Clinical & Translational Science and Orthopedic Surgery, Creighton 
      University School of Medicine, Omaha, NE, 68178, USA. dkagr@creighton.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180611
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (HMGB1 Protein)
RN  - 0 (Hbp1 protein, rat)
RN  - 0 (Inflammasomes)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (Nlrp3 protein, rat)
SB  - IM
MH  - Animals
MH  - Disease Models, Animal
MH  - Extracellular Matrix/*metabolism
MH  - HMGB1 Protein/*metabolism
MH  - Histocytochemistry
MH  - Inflammasomes/*metabolism
MH  - Inflammation/*pathology
MH  - Male
MH  - Microscopy, Fluorescence
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/*metabolism
MH  - Rats, Sprague-Dawley
MH  - Rotator Cuff Injuries/*pathology
PMC - PMC5995925
COIS- The authors declare no competing interests.
EDAT- 2018/06/13 06:00
MHDA- 2019/10/11 06:00
PMCR- 2018/06/11
CRDT- 2018/06/13 06:00
PHST- 2018/03/01 00:00 [received]
PHST- 2018/05/31 00:00 [accepted]
PHST- 2018/06/13 06:00 [entrez]
PHST- 2018/06/13 06:00 [pubmed]
PHST- 2019/10/11 06:00 [medline]
PHST- 2018/06/11 00:00 [pmc-release]
AID - 10.1038/s41598-018-27250-2 [pii]
AID - 27250 [pii]
AID - 10.1038/s41598-018-27250-2 [doi]
PST - epublish
SO  - Sci Rep. 2018 Jun 11;8(1):8918. doi: 10.1038/s41598-018-27250-2.