Transcription factor and bone marrow stromal cells in osseointegration of dental implants
1 Division of Oral Biology, Tufts University School of Dental Medicine, Boston, USA
2 Shandong Provincial Key Lab of Oral Biomedicine, School of Stomatology, Shandong University, Jinan, China
3 Shandong Academy of Medical Sciences, Jinan, China
4 Institute of Stomatology, School of Stomatology, Nanjing Medical University, Nanjing China
5 Department of Oral and Maxillofacial Surgery, School of Stomatology, Sichuan University, Chengdu, China
6 Institute Straumann AG, Basel, Switzerland
7 Periodontology and Implant Dentistry, College of Dentistry, New York University, New York City, USA
8 Department of Dentistry, Zhongshan Hospital Affiliated to Fudan University, Shanghai, China
9 Department of Periodontics, University of Texas Health Science Centre at San Antonio, San Antonio, USA
10 Cancer Preventive Material Development Research Centre (CPMDRC) and Institute, College of Oriental Medicine, Kyunghee University, Seoul, South Korea
11 Department of Anatomy and Cell Biology, Tufts University School of Medicine and Sackler Graduate School of Biomedical Sciences, Boston, USA
§、These authors contributed equally to the paper
Abstract
Titanium implants are widely used in dental clinics and orthopaedic surgery. However, bone formation surrounding the implant is relatively slow after inserting the implant. The current study assessed the effects of bone marrow stromal cells (BMSCs) with forced expression of special AT-rich sequence-binding protein 2 (SATB2) on the osseointegration of titanium implants. To determine whether SATB2 overexpression in BMSCs can enhance the osseointegration of implants, BMSCs were infected with the retrovirus encodingSatb2(pBABE-Satb2) and were locally applied to bone defects before implanting the titanium implants in the mouse femur. Seven and twenty-one days after implantation, the femora were isolated for immunohistochemical (IHC) staining, haematoxylin eosin (H&E) staining, real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), and micro-computed tomography (μCT) analysis. IHC staining analysis revealed that SATB2-overexpressing BMSCs were intensely distributed in the bone tissue surrounding the implant. Histological analysis showed that SATB2-overexpressing BMSCs significantly enhanced new bone formation and bone-to-implant contact 3 weeks after implantation. Real-time qRT-PCR results showed that the local delivery of SATB2-overexpressing BMSCs enhanced expression levels of potent osteogenic transcription factors and bone matrix proteins in the implantation sites. μCT analysis demonstrated that SATB2-overexpressing BMSCs significantly increased the density of the newly formed bone surrounding the implant 3 weeks post-operatively. These results conclude that local delivery of SATB2-overexpressing BMSCs significantly accelerates osseointegration of titanium implants. These results provide support for future pharmacological and clinical applications of SATB2, which accelerates bone regeneration around titanium implants.
Keyword
- Implant; special AT-rich sequence-binding protein 2 (SATB2); osseointegration; bone marrow stromal cells (BMSCs)
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