Impact of the complement cascade on posttraumatic cartilage inflammation and degradation.
The limited ability of articular cartilage to recover from injury, remains an unsolved clinical challenge in orthopaedic surgery. Persistent injury of the articular surface can lead to the development of posttraumatic osteoarthritis. The local inflammatory response contributes to the pathogenesis of osteoarthritis by inducing chondrocyte apoptosis and the de-regulation of chondrocyte matrix remodelling. The role of the complement system in contributing to secondary inflammation-mediated cartilage degradation represents a newer field of investigation. The purpose of this review article is to summarize the known complement-mediated actions in cartilage homeostasis and injury. This article focuses on the known effects of complement on secondary chondrocyte apoptosis, and the interplay of the complement system with pro-inflammatory cytokines. Pharmacological therapies related to complement inhibition will be discussed as they potentially represent a new avenue for attenuating the effect of the complement system on cartilage repair.
John
T
T
Department of Trauma and Reconstructive Surgery, Charité University Medical School, Campus Benjamin Franklin, Berlin, Germany. thilo.john@charite.de
Stahel
P F
PF
Morgan
S J
SJ
Schulze-Tanzil
G
G
D000818:Animals; D017209:Apoptosis; D002358:Cartilage, Articular / Q000187:drug effects / Q000276:immunology / Q000293:injuries* / Q000378:metabolism* / Q000503:physiopathology; D019902:Chondrocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D003167:Complement Activation / Q000187:drug effects; D051056:Complement Inactivating Agents / Q000494:pharmacology / Q000627:therapeutic use; D003169:Complement Inactivator Proteins / Q000378:metabolism; D003165:Complement System Proteins / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D007596:Joints / Q000276:immunology / Q000378:metabolism; D010003:Osteoarthritis / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D010012:Osteogenesis / Q000276:immunology; D013582:Synovial Fluid / Q000276:immunology / Q000378:metabolism
D051056:Complement Inactivating Agents; D003169:Complement Inactivator Proteins; D016207:Cytokines; D003165:Complement System Proteins