title: Osteogenic potential of bone marrow stromal cells derived from streptozotocin-induced             diabetic rats.
abstract: Type 1 diabetes mellitus (T1DM) is associated with a series of bone complications,             which are still a great challenge in the clinic. Bone marrow stromal cells (BMSCs)             are crucial to bone remodeling and are attractive candidates for tissue engineering.             Hence, we aimed to investigate whether impaired functions of BMSCs play a role             in the pathogenesis of bone complications associated with T1DM. BMSCs were isolated             from normal and streptozotocin-induced diabetic rats, and their proliferation             and osteogenic differentiation ability were analyzed. Diabetic BMSCs demonstrated             reduced proliferation ability, osteoblast gene expression, alkaline phosphatase             activity and mineralization. Nude mice transplanted with diabetic BMSCs in a calcium             phosphate cement scaffold exhibited reduced new bone formation, as detected by             hematoxylin and eosin staining and immunohistochemistry. These changes may be             partially related to impaired insulin and insulin-like growth factor 1 (IGF-1)             signaling. Weak gene expression of insulin receptor (IR), IGF-1, insulin-like             growth factor 1 receptor (IGF-1R), and insulin receptor substrate-1 (IRS-1) was             observed in the diabetic BMSCs compared with normal BMSCs, together with decreased             protein level of IGF-1, IGF-1R, IRS-1 and phosphorylated extracellular signal-regulated             kinase. Therefore, impaired proliferation and osteogenic potential of BMSCs may             be responsible for bone complications related to T1DM, mediated partially by impaired             insulin and IGF-1 signaling. These findings may provide a new target with which             to devise strategies for therapy.
authors.affiliation: Department of Prosthodontics, Ninth People's Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
authors.forename: Yan-Fang
authors.initials: YF
authors.lastname: Zhao
authors.forename: De-Liang
authors.initials: DL
authors.lastname: Zeng
authors.forename: Lun-Guo
authors.initials: LG
authors.lastname: Xia
authors.forename: Song-Mei
authors.initials: SM
authors.lastname: Zhang
authors.forename: Lian-Yi
authors.initials: LY
authors.lastname: Xu
authors.forename: Xin-Quan
authors.initials: XQ
authors.lastname: Jiang
authors.forename: Fu-Qiang
authors.initials: FQ
authors.lastname: Zhang
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D002113:Calcification, Physiologic; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015870:Gene Expression; D007328:Insulin / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D010012:Osteogenesis / Q000235:genetics; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis / Q000235:genetics; D011972:Receptor, Insulin / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction; D013311:Streptozocin
chemical_list: D007328:Insulin; D013311:Streptozocin; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin; D048049:Extracellular Signal-Regulated MAP Kinases; D000469:Alkaline Phosphatase