Share This Article:

The timing and extent of intraosseous hypoxia in the oxidative stress-induced rat osteonecrosis model

Abstract Full-Text HTML XML Download Download as PDF (Size:344KB) PP. 814-817
DOI: 10.4236/abb.2013.48107    2,221 Downloads   3,528 Views  

ABSTRACT

Using a rat oxidative stress-induced femoral head osteonecrosis model, we determined the presence/ absence and timing of the generation of hypoxia in the femoral head. DL-Buthionine-(S,R)-sulfoximine (BSO) 500 mg/kg was administered intraperitoneally to male Wistar rats. The rats were killed at 1, 3, 6, 12 hours, and 1, 3, 5 days after BSO administration, and the bilateral femora were removed. A group not administered BSO (control group) was also studied (each group n = 5). In the femoral heads of each group, the expression of hypoxia-inducible factor-1 alpha (HIF-1α) as an index of hypoxia was confirmed by the Western blot method, and quantified using analytical software. In the femoral head increased HIF-1α expression was found in all groups from 1 hour after BSO administration (p < 0.05). In particular, in all specimens of the group 3 hours after BSO administration the most intense expression of HIF-1α amounting to about 13-fold of that of control group was noted (p < 0.001). The present results suggested that in the extremely short period of 3 hours after BSO administration hypoxia severe enough to cause osteonecrosis was induced by oxidative stress in the rat femoral head.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Ichiseki, T. , Kaneuji, A. , Kaneko, S. , Ueda, S. , Ueda, Y. , Yonekura, H. , Fukui, K. and Matsumoto, T. (2013) The timing and extent of intraosseous hypoxia in the oxidative stress-induced rat osteonecrosis model. Advances in Bioscience and Biotechnology, 4, 814-817. doi: 10.4236/abb.2013.48107.

References

[1] Ichiseki, T., Matsumoto, T., Nishino, M., Kaneuji, A. and Katsuda, S. (2004) Oxidative stress and vascular permeability in steroid-induced osteonecrosis model. Journal of Orthopaedic Science, 9, 509-519. doi:10.1007/s00776-004-0816-1
[2] Ichiseki, T., Kaneuji, A., Ueda, Y., Kaneko, S., Ueda, S. and Matsumoto, T. (2012) The initial phase of oxidative stress in a steroid-induced osteonecrosis rabbit model. Advances in Bioscience and Biotechnology, 3, 978-982. doi:10.4236/abb.2012.327120
[3] Ichiseki, T., Kaneuji, A., Katsuda, S., Ueda, Y., Sugimori, T. and Matsumoto, T. (2005) DNA oxidation injury in bone early after steroid administration is involved in the pathogenesis of steroid-induced osteonecrosis. Rheumatology (Oxford), 44, 456-460.
[4] Mikami, T., Ichiseki, T., Kaneuji, A., Ueda, Y., Sugimori, T., Fukui, K. and Matsumoto, T. (2010) Prevention of steroid-induced osteonecrosis by intravenous administration of vitamin E in a rabbit model. Journal of Orthopaedic Science, 15, 674-677. doi:10.1007/s00776-010-1516-7
[5] Li, G.Y., Feng, Y., Cheng, T.S., Yin, J.M. and Zang, C.Q. (2013) Edaravone, a novel free radical scavenger, prevents steroid-induced osteonecrosis in rabbits. Rheumatology (Oxford), 52, 438-447. doi:10.1093/rheumatology/kes313
[6] Nozaki, Y., Kumagai, K., Miyata, N. and Niwa, M. (2012) Pravastatin reduced steroid-induced osteonecrosis of the femoral head in SHRP rats. Acta Orthopaedica, 83, 87-92. doi:10.3109/17453674.2011.641103
[7] Ichiseki, T., Kaneuji, A., Ueda, Y., Nakagawa, S., Mikami, T., Fukui, K. and Matsumoto, T. (2011) Osteonecrosis development in a novel rat model characterized by a single application of oxidative stress. Arthritis & Rheumatism, 63, 2138-2141. doi:10.1002/art.30365
[8] Sato, M., Sugano, N., Ohzono, K., Nomura, S., Kitamura, Y., Tsukamoto, Y. and Ogawa, S. (2001) Apoptosis and expression of stress protein (ORP150, HO1) during development of ischaemic osteonecrosis in the rat. The Journal of Bone & Joint Surgery, 83-B, 751-759. doi:10.1302/0301-620X.83B5.10801
[9] Mary, C. (1965) A histological study of avascular necrosis of the femoral fracture. The Journal of Bone & Joint Surgery, 47-B, 749-776.
[10] Hirota, K. and Semenza, G.L. (2005) Regulation of hypoxia inducible factor 1 by prolyl and asparaginyl hydroxylases. Biochemical and Biophysical Research Communications, 338, 610-616. doi:10.1016/j.bbrc.2005.08.193
[11] Semenza, G.L. (2001) HIF-1, O2, and the 3 PHDs: How animal cells signal hypoxia to the nucleus. Cell, 107, 1-3. doi:10.1016/S0092-8674(01)00518-9
[12] Jones Jr., J.P. (1993) Fat embolism, intravascular coagulation, and osteonecrosis. Clinical Orthopaedics and Related Research, 292, 294-308.
[13] Jones Jr., J.P. (1994) Concepts of etiology and early pathogenesis of osteonecrosis. Instructional Course Lectures, 43, 499-512.
[14] Wang, G.J., Sweet, D.E., Reger, S.I. and Thompson, R.C. (1977) Fat-cell changes as a mechanism of avascular necrosis of the femoral head in cortisone treated rabbits. The Journal of Bone & Joint Surgery, 59, 729-735.
[15] Vaupel, P. (2004) The role of hypoxia-inducible factors in tumor progression. Oncologist, 5, 10-17. doi:10.1634/theoncologist.9-90005-10
[16] Rankin, E.R. and Giaccia, A.J. (2008) The role of hypoxia-inducible factors in tumorigenesis. Cell Death Differ, 15, 678-685. doi:10.1038/cdd.2008.21
[17] Jiang, B.H., Semenza, G.L., Bauer, C. and Marti, H.H. (1996) Hypoxia-inducible factor 1 levels vary exponentially over a physiologically relevant range of O2 tension. American Journal of Physiology, 271, 1172-1180.

  
comments powered by Disqus

Copyright © 2020 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.