International Journal of Nanomedicine (2020-04-01)

The Role of Tantalum Nanoparticles in Bone Regeneration Involves the BMP2/Smad4/Runx2 Signaling Pathway

  • Zhang G,
  • Liu W,
  • Wang R,
  • Zhang Y,
  • Chen L,
  • Chen A,
  • Luo H,
  • Zhong H,
  • Shao L

Journal volume & issue
Vol. Volume 15
pp. 2419 – 2435

Abstract

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Guilan Zhang,1,2 Wenjing Liu,3 Ruolan Wang,1 Yanli Zhang,3 Liangjiao Chen,4 Aijie Chen,3 Haiyun Luo,5 Hui Zhong,1 Longquan Shao1,2 1Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Guangzhou 510515, People’s Republic of China; 3Department of Prosthodontics, Stomatological Hospital, Southern Medical University, Guangzhou 510280, People’s Republic of China; 4Department of Orthodontics, Stomatological Hospital, Guangzhou Medical University, Guangzhou, 510150, People’s Republic of China; 5Department of Endodontics, Stomatological Hospital, Southern Medical University, Guangzhou 510280, People’s Republic of ChinaCorrespondence: Longquan ShaoDepartment of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, People’s Republic of ChinaTel +86 (0)20 15989283921Email [email protected]: In recent years, nanomaterials have been increasingly developed and applied in the field of bone tissue engineering. However, there are few studies on the induction of bone regeneration by tantalum nanoparticles (Ta NPs) and no reports on the effects of Ta NPs on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and the underlying mechanisms. The main purpose of this study was to investigate the effects of Ta NPs on bone regeneration and BMSC osteogenic differentiation and the underlying mechanisms.Materials and Methods: The effects of Ta NPs on bone regeneration were evaluated in an animal experiment, and the effects of Ta NPs on osteogenic differentiation of BMSCs and the underlying mechanisms were evaluated in cell experiments. In the animal experiment, hematoxylin-eosin (HE) staining and hard-tissue section analysis showed that Ta NPs promoted bone regeneration, and immunohistochemistry revealed elevated expression of BMP2 and Smad4 in cells cultured with Ta NPs.Results: The results of the cell experiments showed that Ta NPs promoted BMSC proliferation, alkaline phosphatase (ALP) activity, BMP2 secretion and extracellular matrix (ECM) mineralization, and the expression of related osteogenic genes and proteins (especially BMP2, Smad4 and Runx2) was upregulated under culture with Ta NPs. Smad4 expression, ALP activity, ECM mineralization, and osteogenesis-related gene and protein expression decreased after inhibiting Smad4.Conclusion: These data suggest that Ta NPs have an osteogenic effect and induce bone regeneration by activating the BMP2/Smad4/Runx2 signaling pathway, which in turn causes BMSCs to undergo osteogenic differentiation. This study provides insight into the molecular mechanisms underlying the effects of Ta NPs in bone regeneration.Keywords: tantalum nanoparticles, bone regeneration, osteogenic differentiation, Smad4, BMSCs

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