Arthroplasty membrane-derived fibroblasts directly induce osteoclast formation and osteolysis in aseptic loosening.
OBJECTIVE
Both macrophages and fibroblasts are the main cell types found in periprosthetic tissues surrounding failed joint arthroplasties. These fibroblasts are known to express RANKL and to produce TNFalpha, factors which promote osteoclast formation and bone resorption. In this study we have analysed the role that arthroplasty membrane-derived fibroblasts (AFb) play in inducing the generation of bone resorbing osteoclasts.


METHODS
Fibroblasts were isolated from periprosthetic tissues and co-cultured with human monocytes in an osteoclast differentiation assay in the presence or absence of M-CSF and inhibitors of RANKL (OPG) and/or TNFalpha. RANKL expression by AFbs was determined by RT-PCR and the extent of osteoclast differentiation by the expression of TRAP, VNR and evidence of lacunar resorption.


RESULTS
In the presence of M-CSF, large numbers of TRAP(+) and VNR(+) multinucleated cells capable of lacunar resorption, were noted in co-cultures of monocytes and RANKL-expressing AFbs. Cell-cell contact was required for osteoclast formation. The addition of OPG and anti-TNFalpha alone significantly reduced but did not abolish the extent of osteoclast formation, whereas the addition of both together abolished osteoclast formation and lacunar resorption.


CONCLUSIONS
Our results indicate that fibroblasts in periprosthetic tissues are capable of inducing the differentiation of normal human peripheral blood mononuclear cells to mature osteoclasts by a mechanism that involves both RANKL and TNFalpha. Suppression of both RANKL and inflammatory cytokines is likely to be required to control periprosthetic osteolysis.
Sabokbar
A
A
Nuffield Department of Orthopaedic Surgery, Institute of Musculoskeletal Sciences, University of Oxford, UK. afsie.sabokbar@ndos.ox.ac.uk
Itonaga
I
I
Sun
S G
SG
Kudo
O
O
Athanasou
N A
NA
D000368:Aged; D000369:Aged, 80 and over; D001178:Arthroplasty; D002352:Carrier Proteins / Q000502:physiology; D005260:Female; D005347:Fibroblasts / Q000502:physiology*; D006023:Glycoproteins / Q000494:pharmacology; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000502:physiology; D008875:Middle Aged; D010010:Osteoclasts / Q000502:physiology*; D010014:Osteolysis / Q000209:etiology*; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D002352:Carrier Proteins; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; D014409:Tumor Necrosis Factor-alpha