Acute BMP2 upregulation following induction of ischemic osteonecrosis in immature femoral head

Nobuhiro Kamiya, Sasha Shafer, Ila Oxendine, Douglas P. Mortlock, Ronald L. Chandler, Leif Oxburgh, Harry K W Kim

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Juvenile ischemic osteonecrosis of the femoral head (IOFH) is one of the most serious hip conditions causing the femoral head deformity. Little is known about BMP signaling following ischemic osteonecrosis. In this study, we found acute BMP2 upregulation in the femoral head cartilage 24h after ischemic induction using our immature pig IOFH model. Similarly, in our ischemic osteonecrosis mouse model, BMP2 expression and BMP signaling were enhanced in the articular cartilage surrounding the necrotic bone. BMP2 was increased in cartilage explants and primary chondrocytes under hypoxia (1% O2) compared with normoxia (21% O2). Addition of the hypoxia inducible factor 1 (HIF1) activator DFO significantly increased BMP2 while HIF1 silencing (siHIF1) only partially reduced BMP2, suggesting other mechanisms of BMP2 upregulation being present. Hypoxia is known to induce the production of free oxygen radicals, which are converted to hydrogen peroxide (H2O2) by superoxide dismutase 2 (SOD2). As an alternative mechanism, we investigated the effect of H2O2/SOD2 production on BMP2 upregulation. Chondrocytes produced more H2O2 under hypoxia than normoxia. H2O2 addition to the chondrocyte culture also significantly increased BMP2 expression. SOD2 was also dramatically increased in the ischemic pig cartilage at 24h following surgery and in primary chondrocytes/cartilage explants culture under hypoxia. SOD2 protein addition to the chondrocyte culture significantly increased BMP2. Moreover, DFO significantly increased SOD2 while HIF1 silencing only partially reduced SOD2. These results suggest that the acute BMP2 response of chondrocytes to ischemic osteonecrosis is more dominantly through the H2O2 production and only partly through the HIF1 pathway.

Original languageEnglish (US)
Pages (from-to)239-247
Number of pages9
JournalBone
Volume53
Issue number1
DOIs
Publication statusPublished - Mar 2013

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Keywords

  • Avascular necrosis
  • BMP2
  • Chondrocytes
  • Free oxygen radicals
  • HO
  • Ischemic osteonecrosis

ASJC Scopus subject areas

  • Physiology
  • Endocrinology, Diabetes and Metabolism
  • Histology

Cite this

Kamiya, N., Shafer, S., Oxendine, I., Mortlock, D. P., Chandler, R. L., Oxburgh, L., & Kim, H. K. W. (2013). Acute BMP2 upregulation following induction of ischemic osteonecrosis in immature femoral head. Bone, 53(1), 239-247. https://doi.org/10.1016/j.bone.2012.11.023