Regulation of bone cells by particle-activated mononuclear phagocytes.
Bone loss around replacement prostheses may be related to the activation of mononuclear phagocytes (MNP) by prosthetic wear particles. We investigated how osteoblast-like cells were regulated by human MNP stimulated by particles of prosthetic material. Particles of titanium-6-aluminium-4-vanadium (TiAIV) stimulated MNP to release interleukin (IL)-1beta, tumour necrosis factor (TNF)alpha, IL-6 and prostaglandin E2 (PGE2). All these mediators are implicated in regulating bone metabolism. Particle-activated MNP inhibited bone cell proliferation and stimulated release of IL-6 and PGE2. The number of cells expressing alkaline phosphatase, a marker associated with mature osteoblastic cells, was reduced. Experiments with blocking antibodies showed that TNFalpha was responsible for the reduction in proliferation and the numbers of cells expressing alkaline phosphatase. By contrast, IL-1beta stimulated cell proliferation and differentiation. Both IL-1beta and TNFalpha stimulated IL-6 and PGE2 release from the osteoblast-like cells. Our results suggest that, particle-activated mononuclear phagocytes can induce a change in the balance between bone formation and resorption by a number of mechanisms.
Haynes
D R
DR
University of Adelaide and the Royal Adelaide Hospital, Australia.
Hay
S J
SJ
Rogers
S D
SD
Ohta
S
S
Howie
D W
DW
Graves
S E
SE
D000469:Alkaline Phosphatase / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D000497:Alloys / Q000494:pharmacology*; D000911:Antibodies, Monoclonal; D001862:Bone Resorption / Q000503:physiopathology; D001842:Bone and Bones / Q000166:cytology / Q000378:metabolism; D002450:Cell Communication; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D010006:Osteoblasts / Q000378:metabolism / Q000502:physiology*; D010012:Osteogenesis / Q000502:physiology; D010586:Phagocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D019736:Prostheses and Implants; D014025:Titanium / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000497:Alloys; D000911:Antibodies, Monoclonal; D017077:Culture Media, Conditioned; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; C031462:titanium alloy (TiAl6V4); D014025:Titanium; D000469:Alkaline Phosphatase; D015232:Dinoprostone