Expression of biological mediators during orthodontic tooth movement: A systematic review

•Expression of signaling protein is seen during orthodontic tooth movement.•The mechanobiology of tooth movement is not yet fully understood.•Available in vivo and in vitro studies differ greatly in their methodology.•Although a many proteins are examined, few studies focused on the same one. The aim of the present systematic review was to offer a timeline of the events taking place during orthodontic tooth movement(OTM). Electronic databases PubMed, Web of Science and EMBASE were searched up to November 2017. All studies describing the expression of signaling proteins in the periodontal ligament(PDL) of teeth subjected to OTM or describing the expression of signaling proteins in human cells of the periodontal structures subjected to static mechanical loading were considered eligible for inclusion for respectively the in-vivo or the in-vitro part. Risk of bias assessment was conducted according to the validated SYRCLE’s RoB tool for animal studies and guideline for assessing quality of in-vitro studies for in-vitro studies. We retrieved 7583 articles in the initial electronic search, from which 79 and 51 were finally analyzed. From the 139 protein investigated, only the inflammatory proteins interleukin(IL)-1β, cyclooxygenase(COX)-2 and prostaglandin(PG)-E2, osteoblast markers osteocalcin and runt-related transcription factor(RUNX)2, receptor activator of nuclear factor kappa-B ligand(RANKL) and osteoprotegerin(OPG) and extracellular signal–regulated kinases(ERK)1/2 are investigated in 10 or more studies. The investigated proteins were presented in a theoretical model of OTM. We can conclude that the cell activation and differentiation and recruitment of osteoclasts is mediated by osteocytes, osteoblasts and PDL cells, but that the osteogenic differentiation is only seen in stem cell present in the PDL. In addition, the recently discovered Ephrin/Ephs seem to play an role parallel with the thoroughly investigated RANKL/OPG system in mediating bone resorption during OTM.