간엽줄기세포의 골로의 분화 Osteogenic …

1 Biomaterials Research (2008) 12(2) : 58-6358 BiomaterialsResearchCThe Korean Society for Biomaterials Osteogenic Differentiation of mesenchymal Stem Cells *Hye-Jooung Kim and Gun-Il Im* Dept. of Orthopaedics, Dongguk University International Hospital(Received April 28, 2008/Accepted May 15, 2008) mesenchymal stem cells can be used to regenerate bone in large osseous defect or to treat general disorder in bonemetabolism such as osteogenesis imperfecta. Recent investigations have produced a host of new information andknowledge about bone formations from stem cells. In this review, updates on the Osteogenic differentiations from mes-enchymal stem cells are briefly summarized along with the perspectives on the possible clinical words: Osteogenesis, Mesenchynal stem cell, Differentiation, Tissue engineering.

2 ( mesenchymal stem cell) . (hematopoietic cell) (stromal cell) . , , 1-5) , , , , , (multipotent) .6-9) .. ( Osteogenic differentiation) . (self renewal potential) . , ..10,11) (multilineage differentiation potential) , . , .. Pittenger 1/3 , , 10) 11,12).

3 * : <Review> 59 Vol. 12, No. 2 , , .13) , , , 39000 , , 914, 947, 52 , - 235 , - 3 , - 10 8 . (Figure 1).13) , , , , , , , , . , CD45 CD34 , . , , , . , STRO-1.

4 14) , , .15,16) , , , , , .7,17,19) , (bone substitute) , , , , .19) (BMP) .20-26) , -glycerol-phosphate, ascorbic acid-2-phosphate, dexameth-asone . alkaline phosphatase . von Kossa , bone sialoprotein, osteocalcin,osteopontin Figure 1.

5 The number of candidate genes that are upregulated during MSC commitment into osteogenesis, adipogenesis, and chondrogenesis,and those that are common to two or all three Biomaterials Research 2008 (Figure 2). , . TGF(transforminggrowth factor)- /BMP, Wnt/ -catenin, FGF (fibroblast growthfactor)/IGF(insulin-like growth factor), Hedgehog, Notch .. Runx-2 .TGF- TGF- ,BMP, activin/inhibin group .27,28) BMP-2, BMP-7 . Wnt , 29-31) (osteochondroprogenitor cell) .32,33) (osteopetrosis) .34) FGF 35) IGF.

6 Hedgehog , indian hedgehog (endochondral ossification) .36)Notch BMP .37) Runx-2 (hub) type Icollagen, osteopontine, bone sialoprotein, osteocalcin .38) Runx-2 ..39) Figure 2. Alkaline phosphatase staining (A, B) and Von Kossa staining (C, D) of mesenchymal stem cells cultured in control medium (A, C) andosteogenic medium (B, D). MSCs which differentiated to osteoblasts express alkaline phosphatase and form mineralization nodules. 61 Vol. 12, No. 2 . , , , , ..40) ,41-43) 44,45).

7 46,47) , ..48-53) . , 54-58) .. , .. 40) , , .. 59-61) 61,62) , . , . FGF-2 , ,41) (extracellular matrices).

8 , . 2006 (KRF2006-311-E00359). 1. A. J. Becker, E. A. Mcculloch, and J. E. Till, Cytological demon-stration of the clonal nature of spleen colonies derived fromtransplanted mouse marrow cells, Nature, 452-454 (1963).2. G. J. Spangrude, S. Heimfeld and Weissman, Purificationand characterization ofmouse hematopoietic stem cells, Science, 241, 58-62 (1988).3. H. Ema, T. Suda, H. Nakauchi, Y. Nakamura, A. Iwama, , M. Akutsu, Y. Kano, S. Kato and M. Yabe, et al., Multipotent and committed CD34+ cells in bone marrowtransplantation, Jpn. J. Cancer Res, 82, 547-552 (1991).4. N. Uchida and I. L. Weissman, Searching for hematopoieticstem cells: evidence that Lin- Sca-1+ cells are theonly stem cells in C57 bone marrow, J. Exp. Med.,175, 175-784 (1992).5. C. I. Civin, T. Trischmann, N.

9 S. Kadan, J. Davis, S. Noga, , and B. Duffy, Groenewegen I, Wiley J, Law P, HardwickA, Oldham F, Gee purified CD34-positive cells recon-stitute hematopoiesis, J. Clin. Oncol., 14, 2224-2233 (1996).6. E. S. Strobel, R. E. Gay, and P. L. Greenberg, Characterization ofthe in vitro stromal microenvironment of human bone marrow, Int. J. Cell Cloning, 4, 341-356 (1986).7. D. J. Prockop, Marrow stromal cells as stem cells fornonhematopoietic tissues, Science, 276, 71-74 (1997).8. B. Seshi, S. Kumar, and D. Sellers, Human bone marrowstromal cell: coexpression of markers specific for multiplemesenchymal cell lineages, Blood Cells Mol. Dis., 26, 234-246(2000).9. P. Bianco, M. Riminucci, S. Gronthos, and P. G. Robey, Bone62 Biomaterials Research 2008marrow stromal stem cells: nature, biology, and potentialapplications, Stem Cells, 19, 180-192 (2001).10. M. F. Pittenger, A. M. Mackay, S. C. Beck, R.

10 K. Jaiswal, , J. D. Mosca, M. A. Moorman, D. W. Simonetti, , and D. R. Marshak, Multilineage potential of adulthuman mesenchymal stem cells, Science., 284, 143-147 (1999).11. A. Muraglia, R. Cancedda, and R. Quarto, Clonal mesenchymalprogenitors from human bone marrow differentiate in vitroaccording to a hierarchical model, J Cell Sci., 113, 1161-1166(2000).12. S. A. Kuznetsov, P. H. Krebsbach, K. Satomura, J. Kerr, , D. Benayahu, and P. G. Robey, Single-colonyderived strains of human marrow stromal fibroblasts form boneafter transplantation in vivo, J Bone Miner Res., 12, 1335-47(1997).13. D. Baksh, L. Song, and R. S. Tuan, Adult mesenchymal stemcells: characterization, differentiation, and application in cell andgene therapy, J. Cell Mol. Med., 8, 301-316 (2004).14. F. Liu, L. Malaval, A. K. Gupta, and J. E. Aubin, Simultaneousdetection of multiple bone-related mRNAs and proteinexpression during osteoblast differentiation: polymerase chainreaction and immunocytochemical studies at the single celllevel, Dev.