Osteogenic potential of bone marrow stromal cells derived from streptozotocin-induced diabetic rats

Zhao,Yan-Fang; Zeng,De-Liang; Xia,Lun-Guo; Zhang,Song-Mei; Xu,Lian-Yi; Jiang,Xin-Quan; Zhang,Fu-Qiang

doi:10.3892/ijmm.2013.1227

Osteogenic potential of bone marrow stromal cells derived from streptozotocin-induced diabetic rats

Authors:
- Yan-Fang Zhao
- De-Liang Zeng
- Lun-Guo Xia
- Song-Mei Zhang
- Lian-Yi Xu
- Xin-Quan Jiang
- Fu-Qiang Zhang
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Affiliations: Department of Prosthodontics, Ninth People's Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China, Department of Oral and Maxillofacial Surgery, Ninth People's Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China, Oral Bioengineering Laboratory/Regenerative Medicine Laboratory, Shanghai Research Institute of Stomatology, Shanghai Key Laboratory of Stomatology, Ninth People's Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China
Published online on: January 3, 2013 https://doi.org/10.3892/ijmm.2013.1227
Pages: 614-620

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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.

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