International Journal of Nanomedicine (May 2020)
Magnetic Targeting of HU-MSCs in the Treatment of Glucocorticoid-Associated Osteonecrosis of the Femoral Head Through Akt/Bcl2/Bad/Caspase-3 Pathway
Abstract
Lian Duan,1 Jianlin Zuo,2 Fuqiang Zhang,1 Binxi Li,3 Zhonghang Xu,4 Hao Zhang,3 Bai Yang,3 Wenzhi Song,5 Jinlan Jiang1 1Scientific Research Center, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of China; 2Department of Orthopaedics, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of China; 3State Key Laboratory of Supramolecular Structure and Material, College of Chemistry, Jilin University, Changchun, Jilin, People’s Republic of China; 4Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital, Jilin University, Changchun, Jilin, People’s Republic of China; 5Department of Stomatology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of ChinaCorrespondence: Jinlan Jiang; Wenzhi SongChina-Japan Union Hospital of Jilin University, No. 126 Xian Tai Street, Changchun, Jilin, People’s Republic of ChinaTel|Fax +86 431-84995432Email [email protected]; [email protected]: Osteonecrosis of the femoral head (ONFH) is a chronic and irreversible disease that eventually develops into a joint collapse and results in joint dysfunction. Early intervention and treatment are essential for preserving the joints and avoiding hip replacement. In this study, a system of human umbilical mesenchymal stem cells-supermagnetic iron oxide nanoparticles (NPs) @polydopamine (SCIOPs) was constructed. The magnetic targeting system gathers in the lesion area, inhibits the apoptosis of bone cells, enhances osteogenic effect, and effectively treats ONFH under external magnetic field.Materials and Methods: The supermagnetic iron oxide NPs @polydopamine (SPION@PDA NPs) were characterized by transmission electron microscopy and zeta potential, respectively. The effects of SPION@PDA NPs on the viability, proliferation, and differentiation of stem cells were detected by the CCK8 method, flow cytometry, and staining, respectively. The serum inflammatory indicators were detected by Luminex method. The bone mass of the femoral head was analyzed by micro computed tomography. The expression of apoptosis and osteoblast-related cytokines was detected by Western blotting. The osteogenesis of the femoral head was detected by histological and immunohistochemical sections.Results: The SCIOPs decreased the pro-inflammatory factors, and the micro CT showed that the bone repair of the femoral head was enhanced after treatment. The hematoxylin and eosin sections also showed an increase in the osteogenesis in the femoral head. Western blotting results showed and increased expression of anti-apoptotic proteins Akt and Bcl-2, decreased expression of apoptotic proteins caspase-3 and Bad, and increased expression of osteogenic proteins Runx-2 and Osterix in the femoral head.Conclusion: Under the effect of magnetic field and homing ability of stem cells, SCIOPs inhibited the apoptosis of osteoblasts, improved the proliferation ability of osteoblasts, and promoted bone repair in the femoral head through the Akt/Bcl-2/Bad/caspase-3 signaling pathway, thereby optimizing the tissue repair ability.Keywords: SPION@PDA NPs, HU-MSCs, GC-ONFH, apoptosis
