title: Deferoxamine released from poly(lactic-co-glycolic acid) promotes healing of osteoporotic bone defect via enhanced angiogenesis and osteogenesis.
abstract: The regeneration capacity of osteoporotic bones is generally lower than that of normal bones. Current methods of osteoporotic bone defect treatment are not always satisfactory. Recent studies demonstrate that activation of the hypoxia inducible factor-1α (HIF-1α) pathway, by genetic methods or hypoxia-mimicking agents, could accelerate bone regeneration. However, little is known as to whether modulating the HIF-1α pathway promotes osteoporotic defect healing. To address this problem in the present study, we first demonstrated that HIF-1α and vascular endothelial growth factor expression levels are lower in osteoporotic bones than in normal bones. Second, we loaded poly(Lactic-co-glycolic acid) (PLGA) with the hypoxia-mimetic agent deferoxamine (DFO). DFO released from PLGA had no significant effect on the proliferation of mesenchymal stem cells (MSCs); however, DFO did enhance the osteogenic differentiation of MSCs. In addition, DFO upregulated the mRNA expression levels of angiogenic factors in MSCs. Endothelial tubule formation assays demonstrate that DFO promoted angiogenesis in human umbilical vein endothelial cells. Third, untreated PLGA scaffolds (PLGA group) or DFO-containing PLGA (PLGA + DFO group) were implanted into critically sized osteoporotic femur defects in ovariectomized rats. After treatment periods of 14 or 28 days, micro-CT, histological, CD31 immunohistochemical, and dynamic bone histomorphometric analyses showed that DFO dramatically stimulated bone formation and angiogenesis in a critically sized osteoporotic femur defect model. Our in vitro and in vivo results demonstrate that DFO may promote the healing of osteoporotic bone defects due to enhanced angiogenesis and osteogenesis. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2515-2527, 2016.
authors.affiliation: Department of Orthopaedics, San Xiang Road 1055, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, 215004, China.|Shanghai Institute of Traumatology and Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases with Integrated Chinese Western Medicine, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Rui Jin Er Road 197, Shanghai, 200020, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Jia
authors.affiliation: Department of Orthopaedics, Shanghai Jiao Tong University School of Medicine, Shanghai Ren Ji Hospital, Pu Jian Road 160, Shanghai, 200120, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.affiliation: Shanghai Institute of Traumatology and Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases with Integrated Chinese Western Medicine, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Rui Jin Er Road 197, Shanghai, 200020, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Kang
authors.affiliation: Shanghai Institute of Traumatology and Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases with Integrated Chinese Western Medicine, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Rui Jin Er Road 197, Shanghai, 200020, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Qi
authors.affiliation: Nursing Department, The Second Affiliated Hospital of Soochow University, San Xiang Road 1055, Suzhou, Jiangsu Province, China, 215004.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhao
authors.affiliation: Shanghai Institute of Traumatology and Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases with Integrated Chinese Western Medicine, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Rui Jin Er Road 197, Shanghai, 200020, China.
authors.forename: Min
authors.initials: M
authors.lastname: Jiang
authors.affiliation: Shanghai Institute of Traumatology and Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases with Integrated Chinese Western Medicine, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Rui Jin Er Road 197, Shanghai, 200020, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Guo
authors.affiliation: Shanghai Institute of Traumatology and Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases with Integrated Chinese Western Medicine, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Rui Jin Er Road 197, Shanghai, 200020, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Shanghai Institute of Traumatology and Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases with Integrated Chinese Western Medicine, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Rui Jin Er Road 197, Shanghai, 200020, China.
authors.forename: Nian Dong
authors.initials: ND
authors.lastname: Qian
authors.affiliation: Shanghai Institute of Traumatology and Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases with Integrated Chinese Western Medicine, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Rui Jin Er Road 197, Shanghai, 200020, China.
authors.forename: Han Bing
authors.initials: HB
authors.lastname: Zhou
authors.affiliation: Department of Orthopaedics, San Xiang Road 1055, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, 215004, China.
authors.forename: You Jia
authors.initials: YJ
authors.lastname: Xu
authors.affiliation: Department of Orthopaedics, Huadong Hospital Affiliated Fudan University, Yan'an Western Road 221, Shanghai 200040, China.
authors.forename: Yongqian
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Shanghai Institute of Traumatology and Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases with Integrated Chinese Western Medicine, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Rui Jin Er Road 197, Shanghai, 200020, China.
authors.forename: Lian Fu
authors.initials: LF
authors.lastname: Deng
mesh_terms: D000818:Animals; D001861:Bone Regeneration / Q000187:drug effects; D002478:Cells, Cultured; D003676:Deferoxamine / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005269:Femur / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis / Q000378:metabolism; D019344:Lactic Acid / Q000737:chemistry*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010012:Osteogenesis / Q000187:drug effects*; D010024:Osteoporosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D054457:Tissue Scaffolds / Q000737:chemistry*; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003676:Deferoxamine
keywords: angiogenesis; bone defect; deferoxamine; hypoxia inducible factor-1α signaling pathway; osteogenesis; osteoporosis