Ainola M et al. – ADAM8 may be involved in bone destruction in RA because it is upregulated in RA pannus adjacent to developing erosions and enhances maturation of osteoclast-like cells. Methods
Aim was to study the role of ADAM8 (a disintegrin and a metalloproteinase) in osteoclastogenesis in erosive RA and in vitro
ADAM8 protein and mRNA expression was measured in RA pannus and synovitis and compared to osteoarthritic (OA) synovial membrane
Human monocytes were isolated and stimulated with pro-inflammatory cytokines and their ADAM8 expression and surface ADAM8 were measured
Human peripheral blood monocytes and RAW 264.7 mouse monocyte/macrophage cells were stimulated to osteoclast like-cells
Expression of ADAM8 and osteoclastic markers were analyzed
Transfection and siRNA were used to assess the role of ADAM8 in formation of polykaryons
Results
Increased numbers of ADAM8 positive cells were shown particularly in the pannus-cartilage/bone junction close or adjoining to TRAP positive multinucleate cells under formation
Human pannus contained high ADAM8 mRNA copy numbers
Functional studies in vitro disclosed ADAM8 mRNA and protein, which was first converted to a proteolytically active and then to fusion-active form
Gene transfection and siRNA experiments enhanced and inhibited the expression of osteoclast markers and maturation of multinuclear cells, respectively
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