PMID- 23675495 OWN - NLM STAT- MEDLINE DCOM- 20131209 LR - 20211021 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 8 IP - 5 DP - 2013 TI - HIF-1alpha transgenic bone marrow cells can promote tissue repair in cases of corticosteroid-induced osteonecrosis of the femoral head in rabbits. PG - e63628 LID - 10.1371/journal.pone.0063628 [doi] LID - e63628 AB - Although corticosteroid-induced osteonecrosis of the femoral head (ONFH) is common, the treatment for it remains limited and largely ineffective. We examined whether implantation of hypoxia inducible factor-1alpha (HIF-1alpha) transgenic bone marrow cells (BMCs) can promote the repair of the necrotic area of corticosteroid-induced ONFH. In this study, we confirmed that HIF-1alpha gene transfection could enhance mRNA expression of osteogenic genes in BMCs in vitro. Alkaline phosphatase activity assay and alizarin red-S staining indicated HIF-1alpha transgenic BMCs had enhanced osteogenic differentiation capacity in vitro. Furthermore, enzyme linked immunosorbent assay (ELISA) for VEGF revealed HIF-1alpha transgenic BMCs secreted more VEGF as compared to normal BMCs. An experimental rabbit model of early-stage corticosteroid-induced ONFH was established and used for an evaluation of cytotherapy. Transplantation of HIF-1alpha transgenic BMCs dramatically improved the bone regeneration of the necrotic area of the femoral head. The number and volume of blood vessel were significantly increased in the necrotic area of the femoral head compared to the control groups. These results support HIF-1alpha transgenic BMCs have enhanced osteogenic and angiogenic activity in vitro and in vivo. Transplantation of HIF-1alpha transgenic BMCs can potentially promote the repair of the necrotic area of corticosteroid-induced ONFH. FAU - Ding, Hao AU - Ding H AD - Department of Orthopedic Surgery, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, China. FAU - Gao, You-Shui AU - Gao YS FAU - Hu, Chen AU - Hu C FAU - Wang, Yang AU - Wang Y FAU - Wang, Chuan-Gui AU - Wang CG FAU - Yin, Ji-Min AU - Yin JM FAU - Sun, Yuan AU - Sun Y FAU - Zhang, Chang-Qing AU - Zhang CQ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130513 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Adrenal Cortex Hormones) RN - 0 (Hif1a protein, rat) RN - 0 (Hypoxia-Inducible Factor 1, alpha Subunit) RN - 0 (Vascular Endothelial Growth Factor A) RN - EC 3.1.3.1 (Alkaline Phosphatase) SB - IM MH - Adrenal Cortex Hormones MH - Alkaline Phosphatase/genetics/metabolism MH - Animals MH - Bone Marrow Cells/cytology/*metabolism MH - Bone Marrow Transplantation MH - *Bone Regeneration MH - Cell Differentiation MH - Cell Engineering MH - Cells, Cultured MH - Femur Head/*blood supply/metabolism/pathology MH - Femur Head Necrosis/chemically induced/metabolism/pathology/*therapy MH - Gene Expression MH - Hypoxia-Inducible Factor 1, alpha Subunit/*genetics/metabolism MH - Male MH - Neovascularization, Physiologic MH - *Osteogenesis MH - Rabbits MH - Transgenes MH - Vascular Endothelial Growth Factor A/genetics/metabolism PMC - PMC3652809 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2013/05/16 06:00 MHDA- 2013/12/16 06:00 PMCR- 2013/05/13 CRDT- 2013/05/16 06:00 PHST- 2012/10/30 00:00 [received] PHST- 2013/04/04 00:00 [accepted] PHST- 2013/05/16 06:00 [entrez] PHST- 2013/05/16 06:00 [pubmed] PHST- 2013/12/16 06:00 [medline] PHST- 2013/05/13 00:00 [pmc-release] AID - PONE-D-12-33518 [pii] AID - 10.1371/journal.pone.0063628 [doi] PST - epublish SO - PLoS One. 2013 May 13;8(5):e63628. doi: 10.1371/journal.pone.0063628. Print 2013.