DOI QR코드

DOI QR Code

X-ray radiation at low doses stimulates differentiation and mineralization of mouse calvarial osteoblasts

  • Park, Soon-Sun (Department of Orthodontics, Chonbuk National University) ;
  • Kim, Kyoung-A (Department of Oral and Maxillofacial Radiology, School of Dentistry (BK21 Program), Chonbuk National University) ;
  • Lee, Seung-Youp (Department of Orthodontics, Chonbuk National University) ;
  • Lim, Shin-Saeng (Research Center of Bioactive Materials, Chonbuk National University) ;
  • Jeon, Young-Mi (Department of Orthodontics, Chonbuk National University) ;
  • Lee, Jeong-Chae (Department of Orthodontics, Chonbuk National University)
  • Received : 2012.05.04
  • Accepted : 2012.06.26
  • Published : 2012.10.31

Abstract

Radiotherapy is considered to cause detrimental effects on bone tissue eventually increasing bone loss and fracture risk. However, there is a great controversy on the real effects of irradiation itself on osteoblasts, and the mechanisms by which irradiation affects osteoblast differentiation and mineralization are not completely understood. We explored how X-ray radiation influences differentiation and bone-specific gene expression in mouse calvarial osteoblasts. Irradiation at 2 Gy not only increased differentiation and mineralization of the cells, but also upregulated the expression of alkaline phosphatase, type I collagen, osteopontin, and osteocalcin at early stages of differentiation. However, irradiation at higher doses (>2 Gy) did not stimulate osteoblast differentiation, rather it suppressed DNA synthesis by the cells without a toxic effect. Additional experiments suggested that transforming growth factor-beta 1 and runt-transcription factor 2 play important roles in irradiation- stimulated bone differentiation by acting as upstream regulators of bone-specific markers.

Keywords

References

  1. Schultze-Mosgau, S., Lehner, B., Rodel, F., Wehrhan, F., Amann, K., Kopp, J., Thorwarth, M., Nkenke, E. and Grabenbauer, G. (2005) Expression of bone morphogenic protein 2/4, transforming growth factor-beta1, and bone matrix protein expression in healing area between vascular tibia grafts and irradiated bone-experimental model of osteonecrosis. Int. J. Radiat. Oncol. Biol. Phys. 61, 1189-1196. https://doi.org/10.1016/j.ijrobp.2004.12.008
  2. King, A. D., Griffith, J. F., Abrigo, J. M., Leung, S. F., Yau, F. K., Tse, G. M. and Ahuja, A. T. (2010) Osteoradionecrosis of the upper cervical spine: MR imaging following radiotherapy for nasopharyngeal carcinoma. Eur. J. Radiol. 73, 629-635. https://doi.org/10.1016/j.ejrad.2008.12.016
  3. Matsumura, S., Jikko, A., Hiranuma, H., Deguchi, A. and Fuchihata, H. (1996) Effect of X-ray irradiation on proliferation and differentiation of osteoblast. Calcif. Tissue Int. 59, 307-308. https://doi.org/10.1007/s002239900129
  4. Gal, T. J., Munoz-Antonia, T., Muro-Cacho, C. A. and Klotch, D. W. (2000) Radiation effects on osteoblasts in vitro: a potential role in osteoradionecrosis. Arch. Otolaryngol. Head Neck Surg. 126, 1124-1128. https://doi.org/10.1001/archotol.126.9.1124
  5. He, J., Qiu, W., Zhang, Z., Wang, Z., Zhang, X. and He, Y. (2011) Effects of irradiation on growth and differentiation- related gene expression in osteoblasts. J. Craniofac. Surg. 22, 1635-1640. https://doi.org/10.1097/SCS.0b013e31822e5f66
  6. Shinozaki, K., Hosokawa, Y., Hazawa, M., Kashiwakura, I., Okumura, K., Kaku, T. and Nakayama, E. (2011) Ascorbic acid enhances radiation-induced apoptosis in an HL60 human leukemia cell line. J. Radiat. Res. (Tokyo). 52, 229-237. https://doi.org/10.1269/jrr.10089
  7. Li, J., Kwong, D. L. and Chan, G. C. (2007) The effects of various irradiation doses on the growth and differentiation of marrow- derived human mesenchymal stromal cells. Pediatr. Transplant. 11, 379-387. https://doi.org/10.1111/j.1399-3046.2006.00663.x
  8. Chae, H. J., Chae, S. W., Kang, J. S., Bang, B. G., Han, J. I., Moon, S. R., Park, R. K., So, H. S., Jee, K. S., Kim, H. M. and Kim, H. R. (1999) Effect of ionizing radiation on the differentiation of ROS 17/2.8 osteoblasts through free radicals. J. Radiat. Res. (Tokyo). 40, 323-335. https://doi.org/10.1269/jrr.40.323
  9. Lau, P., Baumstark-Khan, C., Hellweg, C.E. and Reitz, G. (2010) X-irradiation-induced cell cycle delay and DNA double- strand breaks in the murine osteoblastic cell line OCT-1. Radiat. Environ. Biophys. 49, 271-280. https://doi.org/10.1007/s00411-010-0272-6
  10. Choi, J. Y., Lee, B. H., Song, K. B., Park, R. W., Kim, I. S., Sohn, K. Y., Jo, J. S. and Ryoo, H. M. (1996) Expression patterns of bone-related proteins during osteoblastic differentiation in MC3T3-E1 cells. J. Cell Biochem. 61, 609-618. https://doi.org/10.1002/(SICI)1097-4644(19960616)61:4<609::AID-JCB15>3.0.CO;2-A
  11. Sawajiri, M., Nomura, Y., Bhawal, U. K., Nishikiori, R., Okazaki, M., Mizoe, J. and Tanimoto, K. (2006) Different effects of carbon ion and gamma-irradiation on expression of receptor activator of NF-kB ligand in MC3T3-E1 osteoblast cells. Bull. Exp. Biol. Med. 142, 618-624. https://doi.org/10.1007/s10517-006-0433-4
  12. Dudziak, M. E., Saadeh, P. B., Mehrara, B. J., Steinbrech, D. S., Greenwald, J. A., Gittes, G. K. and Longaker, M. T. (2000) The effects of ionizing radiation on osteoblast-like cells in vitro. Plast. Reconstr. Surg. 106, 1049-1061. https://doi.org/10.1097/00006534-200010000-00015
  13. Delanian, S., Porcher, R., Rudant, J. and Lefaix, J. L. (2005) Kinetics of response to long-term treatment combining pentoxifylline and tocopherol in patients with superficial radiation-induced fibrosis. J. Clin. Oncol. 23, 8570-8579. https://doi.org/10.1200/JCO.2005.02.4729
  14. Gevorgyan, A., La Scala, G. C., Neligan, P. C., Pang, C. Y. and Forrest, C. R. (2007) Radiation-induced craniofacial bone growth disturbances. J. Craniofac. Surg. 18, 1001-1007. https://doi.org/10.1097/scs.0b013e31812f7584
  15. O'Dell, K. and Sinha, U. (2011) Osteoradionecrosis. Oral. Maxillofac. Surg. Clin. North. Am. 23, 455-464. https://doi.org/10.1016/j.coms.2011.04.011
  16. Sawajiri, M., Takinami, S., Uchida, T., Nomura, Y., Mizoe, J., Banik, S. and Tanimoto, K. (2007) Expression of MMP-13 in osteoblast cells and rat tibia after exposure to gamma rays or accelerated carbon ions. Phys. Med. 23, 73-79. https://doi.org/10.1016/j.ejmp.2007.03.005
  17. Dare, A., Hachisu, R., Yamaguchi, A., Yokose, S., Yoshiki, S. and Okano, T. (1997) Effects of ionizing radiation on proliferation and differentiation of osteoblast-like cells. J. Dent. Res. 76, 658-664. https://doi.org/10.1177/00220345970760020601
  18. Camozzi, V., Tossi, A., Simoni, E., Pagani, F., Francucci, C.M. and Moro, L. (2007) Role of biochemical markers of bone remodeling in clinical practice. J. Endocrinol. Invest. 30, 13-17. https://doi.org/10.1007/BF03347390
  19. Ducy, P. (2011) The role of osteocalcin in the endocrine cross-talk between bone remodelling and energy metabolism. Diabetologia 54, 1291-1297. https://doi.org/10.1007/s00125-011-2155-z
  20. Tokuyama, R., Satomura, K., Maeda, E., Kudoh, K., Yamasaki, Y. and Nagayama, M. (2007) Maspin is involved in bone matrix maturation by enhancing the accumulation of latent TGF-beta. J. Bone Miner. Res. 22, 1581-1591. https://doi.org/10.1359/jbmr.070611
  21. Miyazono, K., Maeda, S. and Imamura, T. (2004) Coordinate regulation of cell growth and differentiation by TGF-beta superfamily and Runx proteins. Oncogene 23, 4232-4237. https://doi.org/10.1038/sj.onc.1207131
  22. Langdahl, B. L., Carstens, M., Stenkjaer, L. and Eriksen, E. F. (2003) Polymorphisms in the transforming growth factor beta 1 gene and osteoporosis. Bone 32, 297-310. https://doi.org/10.1016/S8756-3282(02)00971-7
  23. Sowa, H., Kaji, H., Yamaguchi, T., Sugimoto, T. and Chihara, K. (2002) Activations of ERK1/2 and JNK by transforming growth factor beta negatively regulate Smad3-induced alkaline phosphatase activity and mineralization in mouse osteoblastic cells. J. Biol. Chem. 277, 36024-36031. https://doi.org/10.1074/jbc.M206030200
  24. Stein, G. S. and Lian, J. B. (1993) Molecular mechanisms mediating proliferation/differentiation interrelationships during progressive development of the osteoblast phenotype. Endocr. Rev. 14, 424-442. https://doi.org/10.1210/edrv-14-4-424
  25. Baek, W. Y. and Kim, J. E. (2011) Transcriptional regulation of bone formation. Front. Biosci. (Schol Ed). 3, 126-135. https://doi.org/10.2741/s138
  26. Komori, T. (2011) Signaling networks in RUNX2- dependent bone development. J. Cell Biochem. 112, 750-755. https://doi.org/10.1002/jcb.22994
  27. Jeong, J. H. and Choi, J. Y. (2011) Interrelationship of Runx2 and estrogen pathway in skeletal tissues. BMB Rep. 44, 613-618. https://doi.org/10.5483/BMBRep.2011.44.10.613
  28. Kim, H. N., Min, W. K., Jeong, J. H., Kim, S. G., Kim, J. R., Kim, S. Y., Choi, J. Y. and Park, B. C. (2011) Combination of Runx2 and BMP2 increases conversion of human ligamentum flavum cells into osteoblastic cells. BMB Rep. 44, 446-451. https://doi.org/10.5483/BMBRep.2011.44.7.446
  29. Ito, Y. and Miyazono, K. (2003) RUNX transcription factors as key targets of TGF-beta superfamily signaling. Curr. Opin. Genet. Dev. 13, 43-47. https://doi.org/10.1016/S0959-437X(03)00007-8
  30. Alliston, T., Choy, L., Ducy, P., Karsenty, G. and Derynck, R. (2001) TGF-beta-induced repression of CBFA1 by Smad3 decreases cbfa1 and osteocalcin expression and inhibits osteoblast differentiation. EMBO. J. 20, 2254-2272. https://doi.org/10.1093/emboj/20.9.2254

Cited by

  1. Low-Dose X-Ray Irradiation Promotes Osteoblast Proliferation, Differentiation and Fracture Healing vol.9, pp.8, 2014, https://doi.org/10.1371/journal.pone.0104016
  2. Activation of canonical Wnt/β-catenin signaling inhibits H2O2-induced decreases in proliferation and differentiation of human periodontal ligament fibroblasts vol.411, pp.1-2, 2016, https://doi.org/10.1007/s11010-015-2570-4
  3. Local delivery of COMP-angiopoietin 1 accelerates new bone formation in rat calvarial defects vol.103, pp.9, 2015, https://doi.org/10.1002/jbm.a.35439
  4. DNA–PKcs–SIN1 complexation mediates low-dose X-ray irradiation (LDI)-induced Akt activation and osteoblast differentiation vol.453, pp.3, 2014, https://doi.org/10.1016/j.bbrc.2014.09.088
  5. Increased EZH2 and decreased osteoblastogenesis during local irradiation-induced bone loss in rats vol.6, pp.1, 2016, https://doi.org/10.1038/srep31318
  6. Differences in responses to X-ray exposure between osteoclast and osteoblast cells 2017, https://doi.org/10.1093/jrr/rrx026
  7. Raman spectroscopy demonstrates prolonged alteration of bone chemical composition following extremity localized irradiation vol.57, pp.1, 2013, https://doi.org/10.1016/j.bone.2013.08.014
  8. A report from Fukushima: an assessment of bone health in an area affected by the Fukushima nuclear plant incident vol.31, pp.6, 2013, https://doi.org/10.1007/s00774-013-0482-5
  9. N-acetyl cysteine inhibits H2O2-mediated reduction in the mineralization of MC3T3-E1 cells by down-regulating Nrf2/HO-1 pathway vol.48, pp.11, 2015, https://doi.org/10.5483/BMBRep.2015.48.11.112
  10. Long-term loss of osteoclasts and unopposed cortical mineral apposition following limited field irradiation vol.33, pp.3, 2015, https://doi.org/10.1002/jor.22761
  11. Irradiation inhibits the maturation and mineralization of osteoblasts via the activation of Nrf2/HO-1 pathway vol.410, pp.1-2, 2015, https://doi.org/10.1007/s11010-015-2559-z
  12. COMP-Ang1 prevents periodontitic damages and enhances mandible bone growth in an experimental animal model vol.92, 2016, https://doi.org/10.1016/j.bone.2016.09.002
  13. Recombinant human IGF-1 produced by transgenic plant cell suspension culture enhances new bone formation in calvarial defects vol.36, 2017, https://doi.org/10.1016/j.ghir.2017.07.003
  14. Therapeutic ionizing radiation induced bone loss: a review of in vivo and in vitro findings vol.59, pp.6, 2018, https://doi.org/10.1080/03008207.2018.1439482
  15. External Beam Irradiation Preferentially Inhibits the Endochondral Pathway of Fracture Healing vol.476, pp.10, 2018, https://doi.org/10.1097/CORR.0000000000000395