OBJECTIVE: Alveolar corticotomy surgery is an adjunctive therapy for reducing orthodontic treatment duration. The activation pathways of bone resorption involved in the tooth movement (TM) process are directly linked to the receptor activator of the nuclear factor-kB ligand (RANKL). Whether similar molecular pathways through RANKL, are shared by the acceleratory TM process (corticotomy-induced or not), sustained acceleration would therefore be expected with transgenic overexpression of this factor. We hypothesize that maintaining transgenic overexpression of RANKL will accelerate TM under force over time rather than at the beginning of therapy only; this contrasts with the corticotomy procedure. MATERIAL AND METHODS: We transfected the pcDNA3.1(+)-mRANKL transgene in vitro into NIH3T3 cells, then evaluated by PCR, Western blot and ex vivo resorption assay. Quantification of RANKL immunofluorescence, fluorescence-based tartrate-resistant acid phosphatase+ (TRAP+) osteoclast counts and histological analyses of the bone resorption area were performed and clinically correlated after a 32-day in vivo experiment comparing corticotomy and gene therapy. RESULTS: In vitro experiments resulted in increased level of RANKL protein (46%, p<0.05) and greater mineral resorption (39%, p<0.05) compared to the controls. In vivo results showed increased RANKL immunoexpression for both corticotomy (twofold) and transfection groups (threefold) after 10 days. After 32 days, a similar result was obtained for the transfected group but not for the surgery group. These data correlate with the clinical effect of decelerating TM in the surgery group. CONCLUSIONS: Selective gene therapy with RANKL has been experimentally tested as an alternative method to corticotomy surgery, showing higher effectiveness than surgical methods used for acceleratory purposes in orthodontics.
OBJECTIVE: Alveolar corticotomy surgery is an adjunctive therapy for reducing orthodontic treatment duration. The activation pathways of bone resorption involved in the tooth movement (TM) process are directly linked to the receptor activator of the nuclear factor-kB ligand (RANKL). Whether similar molecular pathways through RANKL, are shared by the acceleratory TM process (corticotomy-induced or not), sustained acceleration would therefore be expected with transgenic overexpression of this factor. We hypothesize that maintaining transgenic overexpression of RANKL will accelerate TM under force over time rather than at the beginning of therapy only; this contrasts with the corticotomy procedure. MATERIAL AND METHODS: We transfected the pcDNA3.1(+)-mRANKL transgene in vitro into NIH3T3 cells, then evaluated by PCR, Western blot and ex vivo resorption assay. Quantification of RANKL immunofluorescence, fluorescence-based tartrate-resistant acid phosphatase+ (TRAP+) osteoclast counts and histological analyses of the bone resorption area were performed and clinically correlated after a 32-day in vivo experiment comparing corticotomy and gene therapy. RESULTS: In vitro experiments resulted in increased level of RANKL protein (46%, p<0.05) and greater mineral resorption (39%, p<0.05) compared to the controls. In vivo results showed increased RANKL immunoexpression for both corticotomy (twofold) and transfection groups (threefold) after 10 days. After 32 days, a similar result was obtained for the transfected group but not for the surgery group. These data correlate with the clinical effect of decelerating TM in the surgery group. CONCLUSIONS: Selective gene therapy with RANKL has been experimentally tested as an alternative method to corticotomy surgery, showing higher effectiveness than surgical methods used for acceleratory purposes in orthodontics.
Authors: Joy H Chang; Po-Jung Chen; Michael R Arul; Eliane H Dutra; Ravindra Nanda; Sangamesh G Kumbar; Sumit Yadav Journal: Eur J Orthod Date: 2020-06-23 Impact factor: 3.075