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Biology and Potential Use of Chicken Bone Marrow-derived Cells

  • Ko, Dongwoo (Department of Agricultural Biotechnology, Seoul National University) ;
  • Lim, Jeong Mook (Department of Agricultural Biotechnology, Seoul National University)
  • 투고 : 2017.12.22
  • 심사 : 2018.03.27
  • 발행 : 2018.03.31

초록

Developmental aspects of chicken embryos showed dramatic difference compared with those of mammals and consequently, such difference in various developmental events leads to different feasibility in both clinical and industrial application. We have concentrated on the studies for using of chicken bone marrow cells and currently we found number of unique cellular properties. Through this article, we reviewed characteristics and cell signaling of osteogenic cells during endochondral ossification in chicken long bone.

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참고문헌

  1. Aigner, T., Dietz, U., Stoss, H., & von der Mark, K. (1995). Differential expression of collagen types I, II, III, and X in human osteophytes. Lab Invest, 73(2), 236-243.
  2. Akiyama, H., Chaboissier, M. C., Martin, J. F., Schedl, A., & de Crombrugghe, B. (2002). The transcription factor Sox9 has essential roles in successive steps of the chondrocyte differentiation pathway and is required for expression of Sox5 and Sox6. Genes Dev, 16(21), 2813-2828. doi:10.1101/gad.1017802
  3. Akiyama, K., You, Y. O., Yamaza, T., Chen, C., Tang, L., Jin, Y., . . . Shi, S. (2012). Characterization of bone marrow derived mesenchymal stem cells in suspension. Stem Cell Res Ther, 3(5), 40. doi:10.1186/scrt131
  4. Alexander, T., Schneider, S., Hoyer, B., Cheng, Q., Thiel, A., Ziemer, S., . . . Hiepe, F. (2013). Development and resolution of secondary autoimmunity after autologous haematopoietic stem cell transplantation for systemic lupus erythematosus: competition of plasma cells for survival niches? Ann Rheum Dis, 72(6), 1102-1104. doi:10.1136/annrheumdis-2012-202729
  5. Amano, K., Hata, K., Sugita, A., Takigawa, Y., Ono, K., Wakabayashi, M., . . . Yoneda, T. (2009). Sox9 family members negatively regulate maturation and calcification of chondrocytes through up-regulation of parathyroid hormone-related protein. Mol Biol Cell, 20(21), 4541-4551. doi:10.1091/mbc.E09-03-0227
  6. Anbari, F., Khalili, M. A., Bahrami, A. R., Khoradmehr, A., Sadeghian, F., Fesahat, F., & Nabi, A. (2014). Intravenous transplantation of bone marrow mesenchymal stem cells promotes neural regeneration after traumatic brain injury. Neural Regen Res, 9(9), 919-923. doi:10.4103/1673-5374.133133
  7. Aubin, J. E. (2001). Regulation of osteoblast formation and function. Rev Endocr Metab Disord, 2(1), 81-94. https://doi.org/10.1023/A:1010011209064
  8. Campagnoli, C., Roberts, I. A., Kumar, S., Bennett, P. R., Bellantuono, I., & Fisk, N. M. (2001). Identification of mesenchymal stem/progenitor cells in human first-trimester fetal blood, liver, and bone marrow. Blood, 98(8), 2396-2402. https://doi.org/10.1182/blood.V98.8.2396
  9. Chanda, D., Kumar, S., & Ponnazhagan, S. (2010). Therapeutic potential of adult bone marrow-derived mesenchymal stem cells in diseases of the skeleton. J Cell Biochem, 111(2), 249-257. doi:10.1002/jcb.22701
  10. Chen, G., Deng, C., & Li, Y. P. (2012). TGF-beta and BMP signaling in osteoblast differentiation and bone formation. Int J Biol Sci, 8(2), 272-288. doi:10.7150/ijbs.2929
  11. Chen, H., Ghori-Javed, F. Y., Rashid, H., Adhami, M. D., Serra, R., Gutierrez, S. E., & Javed, A. (2014). Runx2 regulates endochondral ossification through control of chondrocyte proliferation and differentiation. J Bone Miner Res, 29(12), 2653-2665. doi:10.1002/jbmr.2287
  12. Chen, S., Gluhak-Heinrich, J., Wang, Y. H., Wu, Y. M., Chuang, H. H., Chen, L., . . . MacDougall, M. (2009). Runx2, osx, and dspp in tooth development. J Dent Res, 88(10), 904-909. doi:10.1177/0022034509342873
  13. Chu, C. R. (2015). The Challenge and the Promise of Bone Marrow Cells for Human Cartilage Repair. Cartilage, 6(2 Suppl), 36S-45S. doi:10.1177/1947603515574839
  14. Chung, U. I. (2004). Essential role of hypertrophic chondrocytes in endochondral bone development. Endocr J, 51(1), 19-24. https://doi.org/10.1507/endocrj.51.19
  15. Csaki, C., Matis, U., Mobasheri, A., Ye, H., & Shakibaei, M. (2007). Chondrogenesis, osteogenesis and adipogenesis of canine mesenchymal stem cells: a biochemical, morphological and ultrastructural study. Histochem Cell Biol, 128(6), 507-520. doi:10.1007/s00418-007-0337-z
  16. Dai, R., Rossello, R., Chen, C. C., Kessler, J., Davison, I., Hochgeschwender, U., & Jarvis, E. D. (2014). Maintenance and neuronal differentiation of chicken induced pluripotent stem-like cells. Stem Cells Int, 2014, 182737. doi:10.1155/2014/182737
  17. Daikeler, T., & Tyndall, A. (2007). Autoimmunity following haematopoietic stem-cell transplantation. Best Pract Res Clin Haematol, 20(2), 349-360. doi:10.1016/j.beha.2006.09.008
  18. Day, T. F., Guo, X., Garrett-Beal, L., & Yang, Y. (2005). Wnt/beta-catenin signaling in mesenchymal progenitors controls osteoblast and chondrocyte differentiation during vertebrate skeletogenesis. Dev Cell, 8(5), 739-750. doi:10.1016/j.devcel. 2005.03.016
  19. Dong, Y. F., Soung do, Y., Schwarz, E. M., O'Keefe, R. J., & Drissi, H. (2006). Wnt induction of chondrocyte hypertrophy through the Runx2 transcription factor. J Cell Physiol, 208(1), 77-86. doi:10.1002/jcp.20656
  20. Eslaminejad, M. B., Fani, N., & Shahhoseini, M. (2013). Epigenetic regulation of osteogenic and chondrogenic differentiation of mesenchymal stem cells in culture. Cell J, 15(1), 1-10.
  21. Flores-Figueroa, E., Montesinos, J. J., & Mayani, H. (2006). [Mesenchymal stem cell; history, biology and clinical application]. Rev Invest Clin, 58(5), 498-511.
  22. Friedenstein, A. J., Chailakhyan, R. K., & Gerasimov, U. V. (1987). Bone marrow osteogenic stem cells: in vitro cultivation and transplantation in diffusion chambers. Cell Tissue Kinet, 20(3), 263-272.
  23. Friedenstein, A. J., Piatetzky, S., II, & Petrakova, K. V. (1966). Osteogenesis in transplants of bone marrow cells. J Embryol Exp Morphol, 16(3), 381-390.
  24. Frisbie, D. D., Lu, Y., Kawcak, C. E., DiCarlo, E. F., Binette, F., & McIlwraith, C. W. (2009). In vivo evaluation of autologous cartilage fragment-loaded scaffolds implanted into equine articular defects and compared with autologous chondrocyte implantation. Am J Sports Med, 37 Suppl 1, 71S-80S. doi:10.1177/0363546509348478
  25. Fujita, T., Azuma, Y., Fukuyama, R., Hattori, Y., Yoshida, C., Koida, M., . . . Komori, T. (2004). Runx2 induces osteoblast and chondrocyte differentiation and enhances their migration by coupling with PI3K-Akt signaling. J Cell Biol, 166(1), 85-95. doi:10.1083/jcb.200401138
  26. Garside, V. C., Cullum, R., Alder, O., Lu, D. Y., Vander Werff, R., Bilenky, M., . . . Hoodless, P. A. (2015). SOX9 modulates the expression of key transcription factors required for heart valve development. Development, 142(24), 4340-4350. doi:10.1242/dev.125252
  27. Goldberg, A., Mitchell, K., Soans, J., Kim, L., & Zaidi, R. (2017). The use of mesenchymal stem cells for cartilage repair and regeneration: a systematic review. J Orthop Surg Res, 12(1), 39. doi:10.1186/s13018-017-0534-y
  28. Gordon, S., Pluddemann, A., & Martinez Estrada, F. (2014). Macrophage heterogeneity in tissues: phenotypic diversity and functions. Immunol Rev, 262(1), 36-55. doi:10.1111/imr.12223
  29. Gregory, C. A., Gunn, W. G., Peister, A., & Prockop, D. J. (2004). An Alizarin red-based assay of mineralization by adherent cells in culture: comparison with cetylpyridinium chloride extraction. Anal Biochem, 329(1), 77-84. doi:10.1016/j.ab.2004.02.002
  30. Guo, X., & Wang, X. F. (2009). Signaling cross-talk between TGF-beta/BMP and other pathways. Cell Res, 19(1), 71-88. doi:10.1038/cr.2008.302
  31. Gurevitch, O., Slavin, S., & Feldman, A. G. (2007). Conversion of red bone marrow into yellow - Cause and mechanisms. Med Hypotheses, 69(3), 531-536. doi:10.1016/j.mehy.2007.01.052
  32. Gurevitch, O., Slavin, S., Resnick, I., Khitrin, S., & Feldman, A. (2009). Mesenchymal progenitor cells in red and yellow bone marrow. Folia Biol (Praha), 55(1), 27-34. https://doi.org/10.3409/173491607780006353
  33. Haaijman, A., D'Souza, R. N., Bronckers, A. L., Goei, S. W., & Burger, E. H. (1997). OP-1 (BMP-7) affects mRNA expression of type I, II, X collagen, and matrix Gla protein in ossifying long bones in vitro. J Bone Miner Res, 12(11), 1815-1823. doi:10.1359/jbmr.1997.12.11.1815
  34. Heim, M., Frank, O., Kampmann, G., Sochocky, N., Pennimpede, T., Fuchs, P., . . . Bendik, I. (2004). The phytoestrogen genistein enhances osteogenesis and represses adipogenic differentiation of human primary bone marrow stromal cells. Endocrinology, 145(2), 848-859. doi:10.1210/en.2003-1014
  35. Heino, T. J., & Hentunen, T. A. (2008). Differentiation of osteoblasts and osteocytes from mesenchymal stem cells. Curr Stem Cell Res Ther, 3(2), 131-145. https://doi.org/10.2174/157488808784223032
  36. Hill, T. P., Spater, D., Taketo, M. M., Birchmeier, W., & Hartmann, C. (2005). Canonical Wnt/beta-catenin signaling prevents osteoblasts from differentiating into chondrocytes. Dev Cell, 8(5), 727-738. doi:10.1016/j.devcel.2005.02.013
  37. Hofstetter, W., Guenther, H. L., Stutzer, A., Schenk, R., Fleisch, H., & Friis, R. (1991). Establishment and characterization of two immortalized cell lines of the osteoblastic lineage. J Bone Miner Res, 6(6), 609-622. doi:10.1002/jbmr.5650060612
  38. Hu, E., Tontonoz, P., & Spiegelman, B. M. (1995). Transdifferentiation of myoblasts by the adipogenic transcription factors PPAR gamma and C/EBP alpha. Proc Natl Acad Sci U S A, 92(21), 9856-9860. https://doi.org/10.1073/pnas.92.21.9856
  39. Hudson, J. E., Mills, R. J., Frith, J. E., Brooke, G., Jaramillo-Ferrada, P., Wolvetang, E. J., & Cooper-White, J. J. (2011). A defined medium and substrate for expansion of human mesenchymal stromal cell progenitors that enriches for osteo- and chondrogenic precursors. Stem Cells Dev, 20(1), 77-87. doi:10.1089/scd.2009.0497
  40. Indrawattana, N., Chen, G., Tadokoro, M., Shann, L. H., Ohgushi, H., Tateishi, T., . . . Bunyaratvej, A. (2004). Growth factor combination for chondrogenic induction from human mesenchymal stem cell. Biochem Biophys Res Commun, 320(3), 914-919. doi:10.1016/j.bbrc.2004.06.029
  41. Jin, X. H., Yang, L., Duan, X. J., Xie, B., Li, Z., & Tan, H. B. (2007). [In vivo MR imaging tracking of supermagnetic iron-oxide nanoparticle-labeled bone marrow mesenchymal stem cells injected into intra-articular space of knee joints: experiment with rabbit]. Zhonghua Yi Xue Za Zhi, 87(45), 3213-3218.
  42. Joyce, M. E., Roberts, A. B., Sporn, M. B., & Bolander, M. E. (1990). Transforming growth factor-beta and the initiation of chondrogenesis and osteogenesis in the rat femur. J Cell Biol, 110(6), 2195-2207. https://doi.org/10.1083/jcb.110.6.2195
  43. Kim, D. H., Yoo, K. H., Choi, K. S., Choi, J., Choi, S. Y., Yang, S. E., . . . Koo, H. H. (2005). Gene expression profile of cytokine and growth factor during differentiation of bone marrow-derived mesenchymal stem cell. Cytokine, 31(2), 119-126. doi:10.1016/j.cyto.2005.04.004
  44. Koch, M., Lemke, A., & Lange, C. (2015). Extracellular Vesicles from MSC Modulate the Immune Response to Renal Allografts in a MHC Disparate Rat Model. Stem Cells Int, 2015, 486141. doi:10.1155/2015/486141
  45. Kolambkar, Y. M., Peister, A., Soker, S., Atala, A., & Guldberg, R. E. (2007). Chondrogenic differentiation of amniotic fluid-derived stem cells. J Mol Histol, 38(5), 405-413. doi:10.1007/s10735-007-9118-1
  46. Komori, T. (2011). Signaling networks in RUNX2-dependent bone development. J Cell Biochem, 112(3), 750-755. doi:10.1002/jcb.22994
  47. Krebsbach, P. H., Kuznetsov, S. A., Bianco, P., & Robey, P. G. (1999). Bone marrow stromal cells: characterization and clinical application. Crit Rev Oral Biol Med, 10(2), 165-181. https://doi.org/10.1177/10454411990100020401
  48. Lang, P., Fritz, R., Vahlensieck, M., Majumdar, S., Berthezene, Y., Grampp, S., & Genant, H. K. (1992). [Residual and reconverted hematopoietic bone marrow in the distal femur. Spin-echo and opposed-phase gradient-echo MRT]. Rofo, 156(1), 89-95. doi:10.1055/s-2008-1032842
  49. Langhans, M. T., Yu, S., & Tuan, R. S. (2016). Stem Cells in Skeletal Tissue Engineering: Technologies and Models. Curr Stem Cell Res Ther, 11(6), 453-474. https://doi.org/10.2174/1574888X10666151001115248
  50. Leung, V. Y., Gao, B., Leung, K. K., Melhado, I. G., Wynn, S. L., Au, T. Y., . . . Cheah, K. S. (2011). SOX9 governs differentiation stage-specific gene expression in growth plate chondrocytes via direct concomitant transactivation and repression. PLoS Genet, 7(11), e1002356. doi:10.1371/journal.pgen.1002356
  51. Li, Y., Yu, X., Lin, S., Li, X., Zhang, S., & Song, Y. H. (2007). Insulin-like growth factor 1 enhances the migratory capacity of mesenchymal stem cells. Biochem Biophys Res Commun, 356(3), 780-784. doi:10.1016/j.bbrc.2007.03.049
  52. Lian, J. B., Javed, A., Zaidi, S. K., Lengner, C., Montecino, M., van Wijnen, A. J., . . . Stein, G. S. (2004). Regulatory controls for osteoblast growth and differentiation: role of Runx/Cbfa/AML factors. Crit Rev Eukaryot Gene Expr, 14(1-2), 1-41. https://doi.org/10.1615/CritRevEukaryotGeneExpr.v14.i12.10
  53. Liu, S. H., Yang, R. S., al-Shaikh, R., & Lane, J. M. (1995). Collagen in tendon, ligament, and bone healing. A current review. Clin Orthop Relat Res(318), 265-278.
  54. LoCascio, S. A., Spinelli, J., & Kurtz, J. (2011). Hematopoietic stem cell transplantation for the treatment of autoimmunity in type 1 diabetes. Curr Stem Cell Res Ther, 6(1), 29-37. https://doi.org/10.2174/157488811794480681
  55. Loebel, C., Czekanska, E. M., Bruderer, M., Salzmann, G., Alini, M., & Stoddart, M. J. (2015). In vitro osteogenic potential of human mesenchymal stem cells is predicted by Runx2/Sox9 ratio. Tissue Eng Part A, 21(1-2), 115-123. doi:10.1089/ten.TEA. 2014.0096
  56. Lu, L., Shen, R. N., & Broxmeyer, H. E. (1996). Stem cells from bone marrow, umbilical cord blood and peripheral blood for clinical application: current status and future application. Crit Rev Oncol Hematol, 22(2), 61-78. https://doi.org/10.1016/1040-8428(96)88370-3
  57. Lv, Y., Liu, B., Wang, H. P., & Zhang, L. (2016). Intramyocardial implantation of differentiated rat bone marrow mesenchymal stem cells enhanced by TGF-beta1 improves cardiac function in heart failure rats. Braz J Med Biol Res, 49(6), e5273. doi:10.1590/1414-431X20165273
  58. Mackay, A. M., Beck, S. C., Murphy, J. M., Barry, F. P., Chichester, C. O., & Pittenger, M. F. (1998). Chondrogenic differentiation of cultured human mesenchymal stem cells from marrow. Tissue Eng, 4(4), 415-428. https://doi.org/10.1089/ten.1998.4.415
  59. Malkiewicz, A., & Dziedzic, M. (2012). Bone marrow reconversion - imaging of physiological changes in bone marrow. Pol J Radiol, 77(4), 45-50. https://doi.org/10.12659/PJR.883628
  60. Mansour, A., Abou-Ezzi, G., Sitnicka, E., Jacobsen, S. E., Wakkach, A., & Blin-Wakkach, C. (2012). Osteoclasts promote the formation of hematopoietic stem cell niches in the bone marrow. J Exp Med, 209(3), 537-549. doi:10.1084/jem.20110994
  61. Merino-Gonzalez, C., Zuniga, F. A., Escudero, C., Ormazabal, V., Reyes, C., Nova-Lamperti, E., . . . Aguayo, C. (2016). Mesenchymal Stem Cell-Derived Extracellular Vesicles Promote Angiogenesis: Potencial Clinical Application. Front Physiol, 7, 24. doi:10.3389/fphys.2016.00024
  62. Moore, S. G., & Dawson, K. L. (1990). Red and yellow marrow in the femur: age-related changes in appearance at MR imaging. Radiology, 175(1), 219-223. doi:10.1148/radiology.175.1.2315484
  63. Morikawa, S., Mabuchi, Y., Kubota, Y., Nagai, Y., Niibe, K., Hiratsu, E., . . . Matsuzaki, Y. (2009). Prospective identification, isolation, and systemic transplantation of multipotent mesenchymal stem cells in murine bone marrow. J Exp Med, 206(11), 2483-2496. doi:10.1084/jem.20091046
  64. Nooeaid, P., Salih, V., Beier, J. P., & Boccaccini, A. R. (2012). Osteochondral tissue engineering: scaffolds, stem cells and applications. J Cell Mol Med, 16(10), 2247-2270. doi:10.1111/j.1582-4934.2012.01571.x
  65. Orlic, D., Kajstura, J., Chimenti, S., Limana, F., Jakoniuk, I., Quaini, F., . . . Anversa, P. (2001). Mobilized bone marrow cells repair the infarcted heart, improving function and survival. Proc Natl Acad Sci U S A, 98(18), 10344-10349. doi:10.1073/pnas.181177898
  66. Ortiz-Nieto, F., Johansson, L., Ahlstrom, H., & Weis, J. (2010). Quantification of lipids in human lower limbs using yellow bone marrow as the internal reference: gender-related effects. Magn Reson Imaging, 28(5), 676-682. doi:10.1016/j.mri.2010.03.014
  67. Pal, B., & Das, B. (2017). In vitro Culture of Naive Human Bone Marrow Mesenchymal Stem Cells: A Stemness Based Approach. Front Cell Dev Biol, 5, 69. doi:10.3389/fcell.2017.00069
  68. Pan, Q., Yu, Y., Chen, Q., Li, C., Wu, H., Wan, Y., . . . Sun, F. (2008). Sox9, a key transcription factor of bone morphogenetic protein-2-induced chondrogenesis, is activated through BMP pathway and a CCAAT box in the proximal promoter. J Cell Physiol, 217(1), 228-241. doi:10.1002/jcp.21496
  69. Parada, C., Li, J., Iwata, J., Suzuki, A., & Chai, Y. (2013). CTGF mediates Smad-dependent transforming growth factor beta signaling to regulate mesenchymal cell proliferation during palate development. Mol Cell Biol, 33(17), 3482-3493. doi:10.1128/MCB.00615-13
  70. Phinney, D. G., & Prockop, D. J. (2007). Concise review: mesenchymal stem/multipotent stromal cells: the state of transdifferentiation and modes of tissue repair--current views. Stem Cells, 25(11), 2896-2902. doi:10.1634/stemcells.2007-0637
  71. Pittenger, M. F., Mackay, A. M., Beck, S. C., Jaiswal, R. K., Douglas, R., Mosca, J. D., . . . Marshak, D. R. (1999). Multilineage potential of adult human mesenchymal stem cells. Science, 284(5411), 143-147. https://doi.org/10.1126/science.284.5411.143
  72. Roark, E. F., & Greer, K. (1994). Transforming growth factor-beta and bone morphogenetic protein-2 act by distinct mechanisms to promote chick limb cartilage differentiation in vitro. Dev Dyn, 200(2), 103-116. doi:10.1002/aja.1002000203
  73. Sakaki-Yumoto, M., Katsuno, Y., & Derynck, R. (2013). TGF-beta family signaling in stem cells. Biochim Biophys Acta, 1830(2), 2280-2296. doi:10.1016/j.bbagen.2012.08.008
  74. Shahi, M., Peymani, A., & Sahmani, M. (2017). Regulation of Bone Metabolism. Rep Biochem Mol Biol, 5(2), 73-82.
  75. Shapiro, F. (2008). Bone development and its relation to fracture repair. The role of mesenchymal osteoblasts and surface osteoblasts. Eur Cell Mater, 15, 53-76. https://doi.org/10.22203/eCM.v015a05
  76. Tavassoli, M., Houchin, D. N., & Jacobs, P. (1977). Fatty acid composition of adipose cells in red and yellow marrow: A possible determinant of haematopoietic potential. Scand J Haematol, 18(1), 47-53. https://doi.org/10.1111/j.1600-0609.1977.tb01476.x
  77. Tevlin, R., Walmsley, G. G., Marecic, O., Hu, M. S., Wan, D. C., & Longaker, M. T. (2016). Stem and progenitor cells: advancing bone tissue engineering. Drug Deliv Transl Res, 6(2), 159-173. doi:10.1007/s13346-015-0235-1
  78. Toma, C., Pittenger, M. F., Cahill, K. S., Byrne, B. J., & Kessler, P. D. (2002). Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart. Circulation, 105(1), 93-98. https://doi.org/10.1161/hc0102.101442
  79. Visvader, J. E., & Stingl, J. (2014). Mammary stem cells and the differentiation hierarchy: current status and perspectives. Genes Dev, 28(11), 1143-1158. doi:10.1101/gad.242511.114
  80. Voronkov, A., & Krauss, S. (2013). Wnt/beta-catenin signaling and small molecule inhibitors. Curr Pharm Des, 19(4), 634-664. https://doi.org/10.2174/138161213804581837
  81. Wagers, A. J., & Weissman, I. L. (2004). Plasticity of adult stem cells. Cell, 116(5), 639-648. https://doi.org/10.1016/S0092-8674(04)00208-9
  82. Wang, C., Meng, H., Wang, X., Zhao, C., Peng, J., & Wang, Y. (2016). Differentiation of Bone Marrow Mesenchymal Stem Cells in Osteoblasts and Adipocytes and its Role in Treatment of Osteoporosis. Med Sci Monit, 22, 226-233. https://doi.org/10.12659/MSM.897044
  83. Woodbury, D., Reynolds, K., & Black, I. B. (2002). Adult bone marrow stromal stem cells express germline, ectodermal, endodermal, and mesodermal genes prior to neurogenesis. J Neurosci Res, 69(6), 908-917. doi:10.1002/jnr.10365
  84. Wu, Z., Xie, Y., Bucher, N. L., & Farmer, S. R. (1995). Conditional ectopic expression of C/EBP beta in NIH-3T3 cells induces PPAR gamma and stimulates adipogenesis. Genes Dev, 9(19), 2350-2363. https://doi.org/10.1101/gad.9.19.2350
  85. Xie, X. J., Wang, J. A., Cao, J., & Zhang, X. (2006). Differentiation of bone marrow mesenchymal stem cells induced by myocardial medium under hypoxic conditions. Acta Pharmacol Sin, 27(9), 1153-1158. doi:10.1111/j.1745-7254.2006.00436.x
  86. Yang, X., Chen, L., Xu, X., Li, C., Huang, C., & Deng, C. X. (2001). TGF-beta/Smad3 signals repress chondrocyte hypertrophic differentiation and are required for maintaining articular cartilage. J Cell Biol, 153(1), 35-46. https://doi.org/10.1083/jcb.153.1.35
  87. Yin, T., & Li, L. (2006). The stem cell niches in bone. J Clin Invest, 116(5), 1195-1201. doi:10.1172/JCI28568
  88. Zakaria, E., & Shafrir, E. (1967). Yellow bone marrow as adipose tissue. Proc Soc Exp Biol Med, 124(4), 1265-1268. https://doi.org/10.3181/00379727-124-31983
  89. Zhang, X., Siclari, V. A., Lan, S., Zhu, J., Koyama, E., Dupuis, H. L., . . . Qin, L. (2011). The critical role of the epidermal growth factor receptor in endochondral ossification. J Bone Miner Res, 26(11), 2622-2633. doi:10.1002/jbmr.502