Analysis of gene expression after orthodontic tooth movement in osteopenic rats treated with doxycycline: in vivo study

Abstract

The restoration of teeth supports tissues after orthodontically induced tooth movement is the major challenge in patients with osteoporosis. It is known that when orthodontic tooth movement is indicated in patients with established osteoporosis, a longer post-treatment time is expected, and exists a correlation between present osteoporosis and mandibular/maxillary trauma stemming from the lack of bone tissue in the region. Objectives: This project aims to compare the use of doxycycline in Wistar rats, in subantimicrobial doses (SDD), which is a known chelating agent of divalent metals (Calcium, for example) and a drug with known bone deposition, the sodium alendronate, which is the standard drug for osteoporosis treatment in the treatment of bone remodeling after orthodontically induced tooth movement (OITM). Materials and methods: 72 Wistar rats will be used divided into 6 groups (n=6), and the groups are defined as follows: C- Control; CDOX - Control exposed to doxycycline 30 mg/kg/day; CAL - Control exposed to sodium alendronate 0.7 mg/kg/week; OVX - Ovariectomized control; OVXDOX - Ovariectomized exposed to doxycycline 30 mg/kg/day; OVXAL - Ovarietomized exposed to sodium alendronate 0.7 mg/kg/week. The rats, about 80 days old, will undergo the osteopenia induction procedure for 90 days. After this period, rats will be treated with doxycycline at a dose of 30 mg/kg/day or sodium alendronate at a dose of 0.7 mg/kg/week, both for 60 days. The total trial period will be 150 days, fourteen and seven days before sacrifice, and all animals will be submitted to orthodontically induced tooth movement (OITM). After 150 days from the beginning of the experiment, euthanasia will be performed. Samples of periodontal support tissues will be subjected to analyses for gene expression (PCR) for the following genes: RANK, RANKL, OPG, osteonectin (ONC), osteocalcin (OCC), bone sialoprotein (BSP), osteopontin (OPN) and bone morphogenetic protein 2 (BMP2). Also, blood plasma will be analyzed for the analysis of bone remodeling biomarkers: type 1 collagen propeptide (P1NP), osteocalcin, alkaline phosphatase, and the presence of C-terminal telopeptide (CTx). Statistical analysis: the results of this project will be submitted to the appropriate statistical test.(AU)