Association of Inflammatory Responses and ECM Disorganization with HMGB1 Upregulation and NLRP3 Inflammasome Activation in the Injured Rotator Cuff Tendon

Finosh G. Thankam, Zachary K. Roesch, Matthew Dilisio, Mohamed M. Radwan, Anuradha Kovilam, R. Michael Gross, Devendra K. Agrawal

Research output: Contribution to journalArticle

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Abstract

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-1β, 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.

LanguageEnglish (US)
Article number8918
JournalScientific Reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018
Externally publishedYes

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Inflammasomes
HMGB1 Protein
Tendon Injuries
Rotator Cuff
Tendons
Extracellular Matrix
Up-Regulation
HMGB Proteins
Rage
Inflammation
Tenotomy
Caspase 1
Rotator Cuff Injuries
Humerus
Pathology
Staining and Labeling

All Science Journal Classification (ASJC) codes

  • General

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Association of Inflammatory Responses and ECM Disorganization with HMGB1 Upregulation and NLRP3 Inflammasome Activation in the Injured Rotator Cuff Tendon. / Thankam, Finosh G.; Roesch, Zachary K.; Dilisio, Matthew; Radwan, Mohamed M.; Kovilam, Anuradha; Gross, R. Michael; Agrawal, Devendra K.

In: Scientific Reports, Vol. 8, No. 1, 8918, 01.12.2018.

Research output: Contribution to journalArticle

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abstract = "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-1β, 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.",
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