title: Angiogenic/osteogenic response of BMMSCs on bone-derived scaffold: effect of hypoxia and role of PI3K/Akt-mediated VEGF-VEGFR pathway.
abstract: Bone tissue deficiency is a common clinical challenge. Tissue-engineered bone constructs are an effective approach for the repair of orthopedic bone defects. Mimicking the essential components of the in vivo microenvironment is an efficient way to develop functional constructs. In this study, bone marrow-derived mesenchymal stromal cells (BMMSCs) were seeded into bone-derived scaffolds, a material with similar structure to natural bone. This was done under hypoxic conditions, an environment that imitates that experienced by BMMSCs in vivo. Our data indicate that hypoxia (5% O2 ) significantly increases the proliferation of BMMSCs seeded in scaffolds. As reflected by highly expressed osteogenesis- and angiogenesis-associated biomarkers, including vascular endothelial growth factor (VEGF), RUNX2, bone morphogenetic protein-2/4 and osteopontin, hypoxia also significantly increases the osteogenic and angiogenic responses of BMMSCs seeded into bone-derived scaffold composites. PI3K/Akt-mediated regulation of VEGF-activated VEGFR1/2 signaling is important for hypoxia-induced proliferative/osteogenic/angiogenic responses in BMMSC cellular scaffolds. The combination of bone-derived scaffolds and hypoxia is conducive to the differentiation of BMMSCs into functional tissue-engineered scaffold composites.
authors.affiliation: Affiliated Hospital of Stomatology, Medical College, Zhejiang University, Hangzhou, People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
authors.forename: Xiaoxu
authors.initials: X
authors.lastname: Guan
authors.forename: Mengfei
authors.initials: M
authors.lastname: Yu
authors.forename: Xinhua
authors.initials: X
authors.lastname: Wang
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Zhu
authors.forename: Chaowei
authors.initials: C
authors.lastname: Wang
authors.forename: Mengliu
authors.initials: M
authors.lastname: Yu
authors.forename: Huiming
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000737:chemistry*; D002454:Cell Differentiation / Q000502:physiology; D015687:Cell Hypoxia; D049109:Cell Proliferation / Q000502:physiology; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D008855:Microscopy, Electron, Scanning; D010012:Osteogenesis / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds / Q000737:chemistry*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D019869:Phosphatidylinositol 3-Kinases
keywords: Bone marrow-derived mesenchymal stromal cells; Bone-derived scaffolds; Hypoxia; PI3K/Akt; Vascular endothelial growth factor