The molecular mechanism of osteoclastogenesis in rheumatoid arthritis.
Bone-resorbing osteoclasts are formed from hemopoietic cells of the monocyte-macrophage lineage under the control of bone-forming osteoblasts. We have cloned an osteoblast-derived factor essential for osteoclastogenesis, the receptor activator of NF-kappaB ligand (RANKL). Synovial fibroblasts and activated T lymphocytes from patients with rheumatoid arthritis also express RANKL, which appears to trigger bone destruction in rheumatoid arthritis as well. Recent studies have shown that T lymphocytes produce cytokines other than RANKL such as IL-17, granulocyte-macrophage colony-stimulating factor and IFN-gamma, which have powerful regulatory effects on osteoclastogenesis. The possible roles of RANKL and other cytokines produced by T lymphocytes in bone destruction are described.
Udagawa
Nobuyuki
N
Department of Biochemistry, Matsumoto Dental University, Nagano, Japan. udagawa@po.mdu.ac.jp
Kotake
Shigeru
S
Kamatani
Naoyuki
N
Takahashi
Naoyuki
N
Suda
Tatsuo
T
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology; D001862:Bone Resorption / Q000503:physiopathology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D003001:Cloning, Molecular; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D010010:Osteoclasts / Q000378:metabolism*; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology
D002352:Carrier Proteins; D016207:Cytokines; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse