Matrix metalloproteinases -1, -2, -3, -7, -8, -12, and -13 in gingival crevicular fluid during orthodontic tooth movement: a longitudinal randomized split-mouth study

Abstract

This randomized split-mouth study aimed to examine the levels of matrix metalloproteinases (MMPs) -1, -2, -3, -7, -8, -12, and -13 in the gingival crevicular fluid (GCF) at different time points during orthodontic tooth movement. A total of 16 healthy orthodontic subjects (7 females, 9 males; mean age, 17.7 years) who needed their first upper premolars extracted were enrolled. One randomly chosen maxillary canine was subjected to a distalizing force and was considered to be the test side. The contralateral canine, which was not subjected to any force but was included in the orthodontic appliance, was used as a control side. GCF sampling was performed at both the mesial (tension) and distal (pressure) test and control sites at baseline, immediately before applying the orthodontic appliance, and after 1 and 24 hours and 7, 14, and 21 days. A multiplexed bead immunoassay was used to analyse the GCF samples. The mean levels of the MMP-1, -2, -3, -7, -8, -12, and -13 were not significantly different between the test and control groups in each time showed. The comparisons between the tension and pressure sites were also not significantly different at each individual time. A few variations focused on MMP-1 and -3, but the expression of MMP-8 was higher than that of the other MMPs. MMPs are released in sufficient quantities such that tooth movement occurs but with no significant increase in GCF levels.

Effect of orthodontic forces on levels of enzymes in gingival crevicular fluid (GCF): A systematic review

“… 59 MMP-9 is responsible for cleavage of denatured collagen, i.e gelatin; 60 MMP-13 dissolves native fibrillar collagen; MMP-1 is an interstitial collagenase hydrolyzing mainly type III collagen, 61 and MMP-3 is responsible for activation of MMPs 8 and 9. 62 Hence peaks of MMP8 and MMP9/NGAL ratio at 14d 17 and 72hr, 13 respectively, occur subsequent to peak of MMP-3 in 1hr/24hr. 17 , 20 In vitro studies also support rise in MMPs in orthodontic forces, specifically MMP-1,2 mRNA and protein production in human gingival and pdl fibroblasts 63 , 64 and MMP-1,2, 9 in gingival tissue of dogs.…”

“… 62 Hence peaks of MMP8 and MMP9/NGAL ratio at 14d 17 and 72hr, 13 respectively, occur subsequent to peak of MMP-3 in 1hr/24hr. 17 , 20 In vitro studies also support rise in MMPs in orthodontic forces, specifically MMP-1,2 mRNA and protein production in human gingival and pdl fibroblasts 63 , 64 and MMP-1,2, 9 in gingival tissue of dogs. 60 …”

“…An initial upregulation in enzymes for bone resorption and matrix degradation like TRAP, ACP or MMPs and an immediate decrease in bone formative ALP corresponded with Burstone’s initial phases of OTM. Different MMPs responsible for extracellular matrix (ECM) breakdown are increased at variable times in OTM, 13 , 15 , 17 , 18 , 20 , 22 , 27 , 50 as early as 1hr or till completion of alignment. 50 MMP-9 increased in 4hr, peaked at 8hr using stainless steel ligatures for canine retraction in one study, while MMP9/NGAL ratio peaked in 72hr in another study.…”

Biomarkers of Orthodontic Tooth Movement in Gingival Crevicular Fluid: A Systematic Review

“…72,[79][80][81][82] The GCF level of MMPs and their inhibitors has been generally shown to peak at an average of 1 to 2 days after the application of the stimulus and return to baseline values after approximately 1 week. [83][84][85] The role of RANKL and its inhibitor OPG in inducing alveolar bone remodeling during orthodontic tooth movement has been demonstrated. 39,40,86 Based on the observations of various studies, it can be concluded that the analysis of GCF mediators reflects the biological activity that occurs in the periodontium during orthodontic tooth movement.…”

Orthodontic force regulates metalloproteinase-3 promoter in osteoblasts and transgenic mouse models

“…Orthodontic loading is an intentional mechanical stimulation using orthodontic devices to increase bone turnover around teeth to achieve the desired positions for improved function and esthetics. An early increase in the signaling of chemokines or cytokines, including Prostaglandin E2 (PGE-2), cyclic adenosine monophosphate (cAMP), tumor necrotic factor-α (TNF-α), interleukin-1 β (IL-1 β) occurs during orthodontic tooth movement (OTM) 1 , 2 , 3 , 4 and the downstream effectors, matrix metalloproteinases (MMPs), exhibit increased expression upon mechanical loading on either the tension or pressure side, 5 , 6 , 7 indicating that MMPs play a critical role in increasing extracellular matrix turnover, a fundamental part of OTM.…”