Full Text:


영남의대학술지 Vol.24_No.2 Suppl. P.S270-276, Dec. 2007




영남대학교 의과대학 미생물학교실
책임저자:정대원, 대구광역시 남구 대명 5동 317-1, 영남대학교 의과대학 미생물학교실
Tel: (053) 620-4365, Fax: (053) 653-6628
E-mail: dwjeong@ynu.ac.kr

December 30, 2007


Bone is the only solid organ and serves as a mechanical support and a reservoir of minerals. Bone homeostasis is achieved by the balance between bone-forming osteoblasts and bone-resorbing osteoclasts. Osteoblasts, which are derived from mesenchymal stem cells, secrete bone matrix proteins and promote mineralization. Otherwise, osteoclasts are derived from hematopoietic stem cells (HSC) that are capable of differentiating into all immune cells and resorb bone matrix by acid decalcification and proteolytic degradation. Osteobalsts and osteoclasts are an important role in the regulation of HSC niche and development, showing that bone remodeling was linked to hematopoietic regulation. Long-lived memory T and B cells and bone cells coexist in the bone marrow reservoir as well as activated T cells that mediate adaptive immune system and osteoclasts that regulate bone turnover share a common molecules that are essential for their development and differentiation. In addition, activated T cell-expressed RANKL directly stimulates osteoclastogenesis. Accumulating evidence indicates that there is the interplay between the immune-related cells and bone remodeling-related cells. This review will discuss the osteoimmunology, an interdisciplinary approach to understanding the cross-talk between bone and the immune cells.

감사의 글
본 종설은 한국과학재단으로부터 영남대학교 노인성혈관질환연구센터에 제공된 기금(R13- 2005-005-01004-0)으로 수행되었다.

Key Words: Bone, Osteoblast, Osteoclast, Immune cells, Osteoimmunology


1. Seeman E, Delmas PD. Bone quality--the material and structural basis of bone strength and fragility. N Engl J Med 2006 May;354: 2250-61.

2. Boisvert CA. The pelvic fin and girdle of Panderichthys and the origin of tetrapod locomotion. Nature 2005 Dec;438:1145-7.

3. Knothe Tate ML, Adamson JR, Tami AE, Bauer TW. The osteocyte. Int J Biochem Cell Biol 2004 Jan;36:1-8.

4. Teitelbaum SL. Bone resorption by osteoclasts. Science 2000 Sep;289:1504-8.

5. Nakashima K, Zhou X, Kunkel G, et al. The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell 2002 Jan;108:17-29.

6. Boyle WJ, Simonet WS, Lacey DL. Osteoclast differentiation and activation. Nature 2003 May;423:337-42.

7. Aubin JE. Regulation of osteoblast formation and function. Rev Endocr Metab Disord 2001 Jan;2:81-94.

8. Yoshida H, Hayashi S, Kunisada T, et al. The murine mutation osteopetrosis is in the coding region of the macrophage colony stimulating factor gene. Nature 1990 May;345:442-4.

9. Arron JR, Choi Y. Bone versus immune system. Nature 2000 Nov;408:535-6.

10. Arai F, Hirao A, Ohmura M, et al. Tie2/ angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche. Cell 2004 Jul;118:149-61.

11. Calvi LM, Adams GB, Weibrecht KW, et al. Osteoblastic cells regulate the haematopoietic stem cell niche. Nature 2003 Oct;425:841-6.

12. Zhang J, Niu C, Ye L, et al. Identification of the haematopoietic stem cell niche and control of the niche size. Nature 2003 Oct;425:836-41.

13. Kollet O, Dar A, Shivtiel S, et al. Osteoclasts degrade endosteal components and promote mobilization of hematopoietic progenitor cells. Nat Med 2006 Jun;12:657-64.

14. Ducy P, Zhang R, Geoffroy V, Ridall AL, Karsenty G. Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell 1997 May;89: 747-54.

15. Celeste AJ, Iannazzi JA, Taylor RC, et al. Identification of transforming growth factor beta family members present in bone-inductive protein purified from bovine bone. Proc Natl Acad Sci U S A 1990 Dec;87:9843-7.

16. Aarden EM, Burger EH, Nijweide PJ. Function of osteocytes in bone. J Cell Biochem 1994 Jul;55:287-99.

17. van der Plas A, Aarden EM, Feijen JH, et al. Characteristics and properties of osteocytes in culture. J Bone Miner Res 1994 Nov;9:1697-704.

18. Suda T, Takahashi N, Udagawa N, Jimi E, Gillespie MT, Martin TJ. Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families. Endocr Rev 1999 Jun;20:345-57.

19. Blair HC, Teitelbaum SL, Ghiselli R, Gluck S. Osteoclastic bone resorption by a polarized vacuolar proton pump. Science 1989 Aug;245: 855-7.

20. James IE, Lark MW, Zembryki D, et al. Development and characterization of a human in vitro resorption assay: demonstration of utility using novel antiresorptive agents. J Bone Miner Res 1999 Sep;14:1562-9.

21. Vaananen HK, Karhukorpi EK, Sundquist K, et al. Evidence for the presence of a proton pump of the vacuolar H(+)-ATPase type in the ruffled borders of osteoclasts. J Cell Biol 1990 Sep;111:1305-11.

22. Kim JM, Min SK, Kim H, et al. Vacuolar- type H+-ATPase-mediated acidosis promotes in vitro osteoclastogenesis via modulation of cell migration. Int J Mol Med 2007 Mar;19: 393-400.

23. Takayanagi H. Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems. Nat Rev Immunol 2007 Apr;7:292-304.

24. Walsh MC, Kim N, Kadono Y, et al. Osteoim- munology: interplay between the immune system and bone metabolism. Annu Rev Immunol 2006;24:33-63.

25. Rho J, Takami M, Choi Y. Osteoimmunology: interactions of the immune and skeletal systems. Mol Cells 2004 Feb;17:1-9.

26. Theill LE, Boyle WJ, Penninger JM. RANK-L and RANK: T cells, bone loss, and mammalian evolution. Annu Rev Immunol 2002;20:795-823.

27. Franzoso G, Carlson L, Xing L, et al. Requirement for NF-kappaB in osteoclast and B-cell development. Genes Dev 1997 Dec;11:3482-96.

28. Asagiri M, Sato K, Usami T, et al. Autoampli- fication of NFATc1 expression determines its essential role in bone homeostasis. J Exp Med 2005 Nov;202:1261-9.

29. Hodgkinson CA, Moore KJ, Nakayama A, et al. Mutations at the mouse microphthalmia locus are associated with defects in a gene encoding a novel basic-helix-loop-helix-zipper protein. Cell 1993 Jul;74:395-404.

30. Sato K, Takayanagi H. Osteoclasts, rheumatoid arthritis, and osteoimmunology. Curr Opin Rheumatol 2006 Jul;18:419-26.

31. Takayanagi H. Inflammatory bone destruction and osteoimmunology. J Periodontal Res 2005 Aug;40:287-93.

32. Palladino MA, Bahjat FR, Theodorakis EA, Moldawer LL. Anti-TNF-alpha therapies: the next generation. Nat Rev Drug Discov 2003 Sep;2:736-46.

33. Madianos PN, Bobetsis YA, Kinane DF. Generation of inflammatory stimuli: how bacteria set up inflammatory responses in the gingiva. J Clin Periodontol 2005;32 Suppl 6: 57-71.