Figure 1. Complement's vicious cycle in osteoarthritis. Joint damage can activate a
self-perpetuating cycle of complement activation and cartilage damage that
leads to osteoarthritis.
damage from injury or surgery releases extracellular matrix (ECM) components [a], such as fibromodulin and aggrecan, into
the synovial fluid that activate the complement system and upregulate complement 5 (C5) [b]. Upon cleavage from C5, C5b recruits
other complement factors (C6-C9)
to form the complement C5b-9 membrane attack complex (MAC) [c] that targets chondrocytes and either
kills them to cause cartilage damage [d] or induces expression of proinflammatory monocyte chemoattractant protein-1 (MCP-1; CCL2), expression of additional C5 and
secretion of ECM-degrading enzymes such as matrix metalloproteinase
metallopeptidase with thrombospondin type 1 motif 5 (ADAMTS5)
thereby continuing the cartilage-damaging cycle [a-e].
a recombinant human minibody against C5 fused with an arginine-glycine-aspartic
acid motif, from Adienne Pharma & Biotech,
is in preclinical testing to treat ischemia/reperfusion injury.
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