Runx2 modified dental pulp stem cells (DPSCs) enhance new bone formation during rapid distraction osteogenesis (DO).
Distraction osteogenesis (DO) remains a major challenge in orthopedic and craniofacial surgery. The transplantion of mesenchymal stem cells (MSCs) could reduce the treatment period and the associated complications by increasing new bone formation during long-bone DO. Runt-related transcription factor 2 (Runx2) encodes a nuclear protein that is a pivotal regulator of osteoblast differentiation. It significantly stimulates calcium accumulation and alkaline phosphatase (ALP) activity in dental pulp stem cells (DPSCs). In this study, we investigated the effects of gene therapy using Runx2 on new bone formation during tibia DO of rabbits. The distraction gap of the rabbits was injected with adenovirus (Adv)-Runx2-green fluorescent protein (GFP)-transfected DPSCs (overexpression group, Group OE) or Adv-GFP-transfected DPSCs (negative control group, Group NC). Rabbits in the control group (Groups CON) were injected with physiologic saline. The generation of new bone tissue in the distraction gap was studied by radiographic examination, micro-computed tomography (CT) evaluation, histological analyze, and Mechanical testing at weeks 8 in the consolidation period. Excellent bone formation in the distracted callus was observed in Group OE and Group NC. Moreover, the OE group showed better bone formation and the highest bone mineral density (BMD) and bone mineral content (BMC). Group CON animals showed inadequate bone formation in the distracted callus compared to the other groups. The results suggest that gene therapy using Runx2-modiﬁed DPSCs was more effective during bone deposition and new bone formation in tibia DO.
Department of Stomatology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province 226001, People's Republic of China.
Guijuan
G
Feng
Department of Spine Surgery, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu Province 226001, People's Republic of China.
Jinlong
J
Zhang
Department of Stomatology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province 226001, People's Republic of China.
Xingmei
X
Feng
Department of Stomatology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province 226001, People's Republic of China.
Senbin
S
Wu
Department of Stomatology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province 226001, People's Republic of China.
Dan
D
Huang
Department of Oral and Maxillofacial Surgery, The State Key Laboratory of Oral Diseases, Sichuan University West China College of Stomatology, Chendgu, Sichuan Province 610041, People's Republic of China.
Jing
J
Hu
Department of Oral and Maxillofacial Surgery, The State Key Laboratory of Oral Diseases, Sichuan University West China College of Stomatology, Chendgu, Sichuan Province 610041, People's Republic of China.
Songsong
S
Zhu
Department of Stomatology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province 226001, People's Republic of China. Electronic address: sdh527@163.com.
Donghui
D
Song
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics*; D003782:Dental Pulp / Q000166:cytology / Q000637:transplantation; D015316:Genetic Therapy; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D008334:Mandible / Q000254:growth & development / Q000601:surgery; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology; D010012:Osteogenesis / Q000235:genetics*; D019857:Osteogenesis, Distraction; D011817:Rabbits; D013977:Tibia / Q000254:growth & development / Q000601:surgery; D055114:X-Ray Microtomography
D050659:Core Binding Factor Alpha 1 Subunit; D049452:Green Fluorescent Proteins
Bone formation; Dental pulp stem cells (DPSCs); Distraction osteogenesis (DO); Runt-related gene 2 (Runx2)