title: Interaction between the immune system and bone metabolism: an emerging field of osteoimmunology.
abstract: The interaction between the immune and bone systems has long been appreciated, but recent research into arthritis as well as various bone phenotypes found in immune-related knockout mice has highlighted the importance of the interplay and the interdisciplinary field called osteoimmunology. In rheumatoid arthritis, IL-17-producing helper T cells (TH17) induces receptor activator of NF-κB ligand (RANKL), which stimulates osteoclast differentiation through nuclear factor of activated T cells (NFAT)c1. Accumulating evidence suggests that the immune and skeletal systems share cytokines, signaling molecules, transcription factors and membrane receptors. In addition, the immune cells are maintained in the bone marrow, which provides a space for mutual interaction. Thus, bone turns out to be a dynamic tissue that is constantly renewed, where the immune system participates to a hitherto unexpected extent. This emerging field of osteoimmunology will be of great importance not only to the better understanding of the two systems but also to the development of new treatment for rheumatic diseases.
authors.affiliation: Department of Cell Signaling, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan . ; Center of Excellence Program for Frontier Research on Molecular Destruction and Reconstruction of Tooth and Bone, Tokyo Medical and Dental University, Tokyo, Japan .
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takayanagi
keywords: NFATc1; RANKL; TH17; osteoclast; osteoimmunology
references.citation: J Immunol. 1997 Jun 1;158(11):5507-13
references.pmid: 9164974
references.citation: Mod Rheumatol. 2007;17(1):17-23
references.pmid: 17278017
references.citation: Nature. 2003 May 15;423(6937):349-55
references.pmid: 12748654
references.citation: Biochem Biophys Res Commun. 1997 Nov 17;240(2):279-86
references.pmid: 9388467
references.citation: Arthritis Rheum. 2005 Apr;52(4):1020-30
references.pmid: 15818697
references.citation: Arthritis Rheum. 2004 Mar;50(3):794-804
references.pmid: 15022321
references.citation: Curr Opin Rheumatol. 2006 Jul;18(4):419-26
references.pmid: 16763464
references.citation: Nature. 2004 Apr 15;428(6984):758-63
references.pmid: 15085135
references.citation: Nat Med. 2005 Aug;11(8):880-5
references.pmid: 16041384
references.citation: J Exp Med. 2005 Sep 5;202(5):589-95
references.pmid: 16147974
references.citation: Biochim Biophys Acta. 1997 Apr 12;1360(2):109-41
references.pmid: 9128178
references.citation: Cell. 2002 Jun 14;109(6):707-18
references.pmid: 12086670
references.citation: Nature. 1999 Jan 28;397(6717):315-23
references.pmid: 9950424
references.citation: Dev Cell. 2002 Dec;3(6):889-901
references.pmid: 12479813
references.citation: J Immunol. 1997 Jun 1;158(11):5501-6
references.pmid: 9164973
references.citation: J Exp Med. 2006 Nov 27;203(12):2673-82
references.pmid: 17088434
references.citation: J Clin Invest. 2002 Nov;110(10):1419-27
references.pmid: 12438440
references.citation: Nat Rev Immunol. 2007 Apr;7(4):292-304
references.pmid: 17380158
references.citation: EMBO J. 2001 Mar 15;20(6):1271-80
references.pmid: 11250893
references.citation: Nature. 1997 Nov 13;390(6656):175-9
references.pmid: 9367155
references.citation: Immunity. 2006 Jun;24(6):677-688
references.pmid: 16782025
references.citation: Science. 1972 Sep 1;177(4051):793-5
references.pmid: 5052733
references.citation: N Engl J Med. 2006 Feb 23;354(8):821-31
references.pmid: 16495394
references.citation: Nature. 1990 May 31;345(6274):442-4
references.pmid: 2188141
references.citation: Am J Pathol. 2001 Nov;159(5):1689-99
references.pmid: 11696430
references.citation: Biochem Biophys Res Commun. 1999 Nov;265(1):144-50
references.pmid: 10548505
references.citation: Cell. 1998 Apr 17;93(2):165-76
references.pmid: 9568710
references.citation: J Exp Med. 2003 Dec 15;198(12):1951-7
references.pmid: 14662908
references.citation: J Clin Invest. 1999 May;103(9):1345-52
references.pmid: 10225978
references.citation: Nature. 1999 Nov 18;402(6759):304-9
references.pmid: 10580503
references.citation: Nat Rev Genet. 2003 Aug;4(8):638-49
references.pmid: 12897775
references.citation: Endocrinology. 1988 Nov;123(5):2600-2
references.pmid: 2844518
references.citation: Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):3597-602
references.pmid: 9520411
references.citation: J Biol Chem. 1997 Oct 3;272(40):25190-4
references.pmid: 9312132
references.citation: Science. 1994 Oct 21;266(5184):443-8
references.pmid: 7939685
references.citation: Cell. 1991 Feb 22;64(4):693-702
references.pmid: 1997203
references.citation: Nat Med. 2006 Dec;12(12):1410-6
references.pmid: 17128269
references.citation: J Clin Invest. 2003 Feb;111(3):323-32
references.pmid: 12569157
references.citation: Nature. 2000 Nov 30;408(6812):600-5
references.pmid: 11117749
references.citation: J Clin Invest. 1999 Jul;104(2):137-46
references.pmid: 10411542
references.citation: J Mol Med (Berl). 2005 Mar;83(3):170-9
references.pmid: 15776286
references.citation: J Clin Invest. 2000 Dec;106(12):1481-8
references.pmid: 11120755
references.citation: J Immunol. 1985 Oct;135(4):2562-8
references.pmid: 3875658
references.citation: Mod Rheumatol. 2005;15(4):225-31
references.pmid: 17029070
references.citation: Arthritis Rheum. 2000 Feb;43(2):250-8
references.pmid: 10693863
references.citation: Annu Rev Immunol. 2006;24:33-63
references.pmid: 16551243
references.citation: Bone. 2007 Feb;40(2):251-64
references.pmid: 17098490
references.citation: J Exp Med. 2005 Nov 7;202(9):1261-9
references.pmid: 16275763
references.citation: Endocr Rev. 1999 Jun;20(3):345-57
references.pmid: 10368775
references.citation: Arthritis Rheum. 2000 Feb;43(2):259-69
references.pmid: 10693864
references.citation: Cell. 1997 Jun 27;89(7):1021-31
references.pmid: 9215625