What are the local and systemic biologic reactions and mediators to wear debris, and what host factors determine or modulate the biologic response to wear particles?
New clinical and basic science data on the cellular and molecular mechanisms by which wear particles stimulate the host inflammatory response have provided deeper insight into the pathophysiology of periprosthetic bone loss. Interactions among wear particles, macrophages, osteoblasts, bone marrow-derived mesenchymal stem cells, fibroblasts, endothelial cells, and T cells contribute to the production of pro-inflammatory and pro-osteoclastogenic cytokines such as TNF-alpha, RANKL, M-SCF, PGE2, IL-1, IL-6, and IL-8. These cytokines not only promote osteoclastogenesis but interfere with osteogenesis led by osteoprogenitor cells. Recent studies indicate that genetic variations in TNF-alpha, IL-1, and FRZB can result in subtle changes in gene function, giving rise to altered susceptibility or severity for periprosthetic inflammation and bone loss. Continuing research on the biologic effects and mechanisms of action of wear particles will provide a rational basis for the development of novel and effective ways of diagnosis, prevention, and treatment of periprosthetic inflammatory bone loss.
Tuan
Rocky S
RS
Cartilage Biology and Orthopaedics Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
Lee
Francis Young-In
FY
T Konttinen
Yrjö
Y
Wilkinson
J Mark
JM
Smith
Robert Lane
RL
D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D001672:Biocompatible Materials / Q000009:adverse effects*; D001862:Bone Resorption / Q000276:immunology*; D015232:Dinoprostone / Q000378:metabolism; D042783:Endothelial Cells / Q000276:immunology; D005347:Fibroblasts / Q000276:immunology; D005549:Foreign-Body Reaction / Q000276:immunology*; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007595:Joint Prosthesis; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D010010:Osteoclasts / Q000276:immunology; D010012:Osteogenesis / Q000276:immunology; D011475:Prosthesis Failure; D053245:RANK Ligand / Q000378:metabolism; D013234:Stem Cells / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D001672:Biocompatible Materials; D015232:Dinoprostone; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D016173:Macrophage Colony-Stimulating Factor; D053245:RANK Ligand; D014409:Tumor Necrosis Factor-alpha; C112467:MSC protein, human; C505688:TNFSF11 protein, human