X-ray radiation at low doses stimulates differentiation and mineralization of mouse calvarial osteoblasts
2
조회
0
다운로드
3
인용
0
참고문헌
키워드
초록
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. [BMB Reports 2012;45(10): 571-576]
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. [BMB Reports 2012;45(10): 571-576]
참고문헌 (30)
- Schultze-Mosgau, S., "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, 2005, pp.61, 1189~1196
- King, A. D., "Osteoradionecrosis of the upper cervical spine: MR imaging following radiotherapy for nasopharyngeal carcinoma", Eur. J. Radiol., 73, pp.629~635 (2010)
- Matsumura, S., "Effect of X-ray irradiation on proliferation and differentiation of osteoblast", Calcif. Tissue Int., 59, pp.307~308 (1996)
- Gal, T. J., "Radiation effects on osteoblasts in vitro: a potential role in osteoradionecrosis", Arch. Otolaryngol. Head Neck Surg., 126, pp.1124~1128 (2000)
- He, J., "Effects of irradiation on growth and differentiation-related gene expression in osteoblasts", J. Craniofac.Surg., 22, pp.1635~1640 (2011)
- Shinozaki, K., "Ascorbic acid enhances radiation-induced apoptosis in an HL60 human leukemia cell line", J. Radiat. Res., 52, pp.229~237 (2011)
- Li, J., "The effects of various irradiation doses on the growth and differentiation of marrow- derived human mesenchymal stromal cells", Pediatr. Transplant., 11, pp.379~387 (2007)
- Chae, H. J., "Effect of ionizing radiation on the differentiation of ROS 17", 2.8 osteoblasts through free radicals, 1999, pp.40, 323~335
- Lau, P., "X-irradiation-induced cell cycle delay and DNA double-strand breaks in the murine osteoblastic cell line OCT-1", Radiat. Environ. Biophys., 49, pp.271~280 (2010)
- Choi, J. Y., "Expression patterns of bone-related proteins during osteoblastic differentiation in MC3T3-E1 cells", J. Cell Biochem., 61, pp.609~618 (1996)
- Sawajiri, M., "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, pp.618~624 (2006)
- Dudziak, M. E., "The effects of ionizing radiation on osteoblast-like cells in vitro", Plast. Reconstr. Surg., 106, pp.1049~1061 (2000)
- Delanian, S., "Kinetics of response to long-term treatment combining pentoxifylline and tocopherol in patients with superficial radiation-induced fibrosis", J. Clin. Oncol., 23, pp.8570~8579 (2005)
- Gevorgyan, A., "Radiation-induced craniofacial bone growth disturbances", J. Craniofac. Surg., 18, pp.1001~1007 (2007)
- O'Dell, K., "Osteoradionecrosis", Oral. Maxillofac. Surg. Clin. North. Am., 23, pp.455~464 (2011)
- Sawajiri, M., "Expression of MMP-13 in osteoblast cells and rat tibia after exposure to gamma rays or accelerated carbon ions", Phys. Med., 23, pp.73~79 (2007)
- Dare, A., "Effects of ionizing radiation on proliferation and differentiation of osteoblast-like cells", J. Dent. Res., 76, pp.658~664 (1997)
- Camozzi, V., "Role of biochemical markers of bone remodeling in clinical practice", J. Endocrinol. Invest., 30, pp.13~17 (2007)
- Ducy, P., "The role of osteocalcin in the endocrine cross-talk between bone remodelling and energy metabolism", Diabetologia, 54, pp.1291~1297 (2011)
- Tokuyama, R., "Maspin is involved in bone matrix maturation by enhancing the accumulation of latent TGF-beta", J. Bone Miner. Res., 22, pp.1581~1591 (2007)
- Miyazono, K., "Coordinate regulation of cell growth and differentiation by TGF-beta superfamily and Runx proteins", Oncogene, 23, pp.4232~4237 (2004)
- Langdahl, B. L., "Polymorphisms in the transforming growth factor beta1 gene and osteoporosis", Bone, 32, pp.297~310 (2003)
- Sowa, H., "Activations of ERK1", 2 and JNK by transforming growth factor beta negatively regulate Smad3-induced alkaline phosphatase activity and mineralization in mouse osteoblastic cells, 2002, pp.277, 36024~36031
- Stein, G. S., "Molecular mechanisms mediating proliferation", differentiation interrelationships during progressive development of the osteoblast phenotype, 1993, pp.14, 424~442
- Baek, W. Y., "Transcriptional regulation of bone formation.", Frontiers in bioscience (Scholar edition), 3(0), pp.126~135 (2011), Frontiers in Bioscience
- Komori, T., "Signaling networks in RUNX2- dependent bone development", J. Cell Biochem., 112, pp.750~755 (2011)
- Jae-Hwan Jeong, "Interrelationship of Runx2 and estrogen pathway in skeletal tissues", BMB Reports, 44(10), pp.613~618 (2011), 생화학분자생물학회
- Hyun-Nam Kim, "Combination of Runx2 and BMP2 increases conversion of human ligamentum flavum cells into osteoblastic cells", BMB Reports, 44(7), pp.446~451 (2011), 생화학분자생물학회
- Ito, Y., "RUNX transcription factors as key targets of TGF-beta superfamily signaling", Curr. Opin. Genet. Dev., 13, pp.43~47 (2003)
- Alliston, T., "TGF-beta-induced repression of CBFA1 by Smad3 decreasescbfa1 and osteocalcin expression and inhibits osteoblastdifferentiation", EMBO. J., 20, pp.2254~2272 (2001)