title: Dimethyloxaloylglycine improves angiogenic activity of bone marrow stromal cells in the tissue-engineered bone.
abstract: One of the big challenges in tissue engineering for treating large bone defects is to promote the angiogenesis of the tissue-engineered bone. Hypoxia inducible factor-1α (HIF-1α) plays an important role in angiogenesis-osteogenesis coupling during bone regeneration, and can activate a broad array of angiogenic factors. Dimethyloxaloylglycine (DMOG) can activate HIF-1α expression in cells at normal oxygen tension. In this study, we explored the effect of DMOG on the angiogenic activity of bone mesenchymal stem cells (BMSCs) in the tissue-engineered bone. The effect of different concentrations of DMOG on HIF-1a expression in BMSCs was detected with western blotting, and the mRNA expression and secretion of related angiogenic factors in DMOG-treated BMSCs were respectively analyzed using qRT-PCR and enzyme linked immunosorbent assay. The tissue-engineered bone constructed with β-tricalcium phosphate (β-TCP) and DMOG-treated BMSCs were implanted into the critical-sized calvarial defects to test the effectiveness of DMOG in improving the angiogenic activity of BMSCs in the tissue-engineered bone. The results showed DMOG significantly enhanced the mRNA expression and secretion of related angiogenic factors in BMSCs by activating the expression of HIF-1α. More newly formed blood vessels were observed in the group treated with β-TCP and DMOG-treated BMSCs than in other groups. And there were also more bone regeneration in the group treated with β-TCP and DMOG-treated BMSCs. Therefore, we believed DMOG could enhance the angiogenic activity of BMSCs by activating the expression of HIF-1α, thereby improve the angiogenesis of the tissue-engineered bone and its bone healing capacity.
authors.affiliation: Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Ding
authors.affiliation: Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Song
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Wen-Qi
authors.initials: WQ
authors.lastname: Song
authors.affiliation: Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: You-Shui
authors.initials: YS
authors.lastname: Gao
authors.affiliation: Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Jun-Jie
authors.initials: JJ
authors.lastname: Guan
authors.affiliation: Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Chang-Qing
authors.initials: CQ
authors.lastname: Zhang
mesh_terms: D000600:Amino Acids, Dicarboxylic / Q000494:pharmacology*; D000818:Animals; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000502:physiology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011916:Rats, Inbred F344; D012886:Skull / Q000637:transplantation; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D000600:Amino Acids, Dicarboxylic; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C040947:oxalylglycine
keywords: angiogenesis; bone marrow stromal cells; bone substitutes; dimethyloxaloylglycine; hypoxia inducible factor-1α