Journal article
DAMPs Synergize with Cytokines or Fibronectin Fragment on Inducing Chondrolysis but Lose Effect When Acting Alone
Mediators of inflammation, Vol.2017, 2642549
07/18/2017
DOI: 10.1155/2017/2642549
PMCID: PMC5540522
PMID: 28804219
Abstract
Objective and Design. To investigate whether endogenous damage-associated molecular patterns (DAMPs) or alarmins originated from mitochondria or nucleus stimulates inflammatory response in articular chondrocytes to cause chondrolysis which leads to cartilage degradation featured in posttraumatic osteoarthritis (PTOA). Materials. Primary cultures of bovine or human chondrocytes isolated from cartilage of weight-bearing joints. Treatment. Chondrocytes were subjected to mitochondrial DAMPs (MTDs) or HMGB1, a nuclear DAMP (NuD), with or without the presence of an N-terminal 29 kDa fibronectin fragment (Fn-f) or proinflammatory cytokines (IL-1β and TNF-α). Injured cartilage-conditioned culturing medium containing a mixture of DAMPs was employed as a control. After 24 hrs, the protein expression of cartilage degrading metalloproteinases and iNOS in culture medium or cell lysates was examined with Western blotting, respectively. Results. HMGB1 was synergized with IL-1β in upregulating expression of MMP-3, MMP-13, ADAMTS-5, ADAM-8, and iNOS. Moreover, a moderate synergistic effect was detected between HMGB1 and Fn-f or between MTDs and TNF-α on MMP-3 expression. However, when acting alone, MTDs or HMGB1 did not upregulate cartilage degrading enzymes or iNOS. Conclusion. MTDs or HMGB1 could only stimulate inflammatory response in chondrocytes with the presence of cytokines or Fn-f.
Details
- Title: Subtitle
- DAMPs Synergize with Cytokines or Fibronectin Fragment on Inducing Chondrolysis but Lose Effect When Acting Alone
- Creators
- Lei Ding - Department of Basic Medical Sciences Jiangnan University Wuxi Medical School Wuxi Jiangsu China jiangnan.edu.cnJoseph A Buckwalter - Department of Orthopaedics and Rehabilitation University of Iowa Hospitals and Clinics Iowa City IA USA uihealthcare.orgJames A Martin - Department of Orthopaedics and Rehabilitation University of Iowa Hospitals and Clinics Iowa City IA USA uihealthcare.org
- Resource Type
- Journal article
- Publication Details
- Mediators of inflammation, Vol.2017, 2642549
- DOI
- 10.1155/2017/2642549
- PMID
- 28804219
- PMCID
- PMC5540522
- NLM abbreviation
- Mediators Inflamm
- ISSN
- 0962-9351
- eISSN
- 1466-1861
- Publisher
- Hindawi
- Grant note
- 1286010242160020 / Jiangnan University Wuxi Medical School P50 AR055533 / National Institutes of Health/NIAMS Department of Veterans Affairs
- Language
- English
- Date published
- 07/18/2017
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Stead Family Department of Pediatrics; Pharmaceutical Sciences and Experimental Therapeutics; Orthopedics and Rehabilitation; Injury Prevention Research Center
- Record Identifier
- 9984040009702771
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