Effect of lentiviral vector overexpression α-calcitonin gene-related peptide on titanium implant osseointegration in α-CGRP-deficient mice.
α-Calcitonin gene-related peptide (α-CGRP) plays a significant pathophysiological role in bone development, metabolism and remodeling around dental implants. However, the half-life of α-CGRP in plasma is only 10min, which affects its long-time application and an alternative approach should be developed to deliver α-CGRP over long periods of time. The aim of this study is to investigate whether a lentiviral α-CGRP overexpression vector system can express this target-gene longer at peri-implant sites, thus enhancing osseointegration. Animals were divided to the following groups: α-CGRP-/-, α-CGRP-/-with lentivirus transfection and α-CGRP+/+mice. IVIS Spectrum imaging observations identified the successful transfection of α-CGRP around experimental implants inserted in the femurs at 5days after injection. Histomorphometrical analysis indicated an increase of bone-implant contact (BIC) at 1-month healing in the transfection group. Moreover, real-time RT-PCR and western blot results of bone-related markers Runx2, Osterix, and BSP levels elevated in lentivirus-transfected mice at 21days, compared to the untreated α-CGRP-/-mice. There was no significant difference between the transfection group and α-CGRP+/+group. Further α-CGRP protein detection confirmed the persistent expression of this transgene at 21days post-operatively. These results suggest that this lentiviral vector system expresses α-CGRP in an effective, appropriate and sustained manner, which might have a potential application in enhancing titanium implant osseointegration.
State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China; Department of Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Lin
L
Xiang
State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China; Department of Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Li
L
Ma
State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China; Department of Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Na
N
Wei
State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China; Department of Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Tianlu
T
Wang
State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China; Department of Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Qianqian
Q
Yao
State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China; Department of Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Bo
B
Yang
State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China; Department of Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Yi
Y
Xiong
State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China; Department of Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Yingying
Y
Wu
State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China; Department of Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, China. Electronic address: dentistgong@hotmail.com.
Ping
P
Gong
D000818:Animals; D015153:Blotting, Western; D015740:Calcitonin Gene-Related Peptide / Q000172:deficiency* / Q000235:genetics*; D005269:Femur / Q000473:pathology; D005822:Genetic Vectors / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D020007:Implants, Experimental; D016086:Lentivirus / Q000378:metabolism*; D051379:Mice; D016348:Osseointegration / Q000187:drug effects*; D010012:Osteogenesis / Q000187:drug effects; D010641:Phenotype; D060888:Real-Time Polymerase Chain Reaction; D014025:Titanium / Q000494:pharmacology*; D014162:Transfection
D049452:Green Fluorescent Proteins; D014025:Titanium; D015740:Calcitonin Gene-Related Peptide
Bone mineralization; Dental implants; Gene therapy; Lentiviral vector; Osseointegration; α-Calcitonin gene-related peptide