Effect of orthodontic forces on cytokine and receptor levels in gingival crevicular fluid: a systematic review

Abstract

This systematic review aimed to generate evidence on role of potent markers of inflammation [cytokines, chemokines, their associated receptors and antagonists] following the application of orthodontic forces. Subsequent to registration with PROSPERO, literature search followed a predetermined search strategy to key databases along with hand search (HS). Seventy-seven articles from PubMed (P), 637 from Scopus (S), 51 from Embase (E), and 3 from hand search (HS) were identified. A total of 39 articles were shortlisted that met strict inclusion and exclusion criteria and quality assessment. Each study was evaluated for participant characteristics, study design, oral hygiene regimen, and gingival crevicular fluid (GCF) handling. Among these studies, biomarkers in the order of frequency were interleukin (IL)-1β (N = 21), tumor necrosis factor (TNF)-α (N = 10), IL-8,IL-6(N=8), receptor activator of nuclear factor kappa-B ligand (RANKL) (N = 7), monocyte chemoattractant protein (MCP)-1 (N = 3), IL-2 (N=4), IL-4, IL-10, RANTES (N = 2), IL-1, IL-5, IL-1α, IP-10, osteopontin (OPN) (N = 1) and receptors and their antagonists in the order of osteoprotegerin (OPG) (N = 8), IL-1RA (N = 5), and RANK (N = 1). Results revealed an immediate release of inflammatory bone-resorptive mediators, IL-1β and TNF-α, where IL-1β increased as early as 1 min to 1 h reaching peak at 24 h while TNF-α increased at 1 h or 1 day. This was accompanied by a fall in bone-protective mediator (OPG) levels at 1 h and 24 h after orthodontic force application. Continuous forces were accompanied by a decrease in mediator levels after attaining peak levels (most commonly at 24 h) while repeated activations in interrupted force upregulated their secretion. Significant correlations of IL-1β levels with pain intensity, rate of orthodontic tooth movement (OTM) and of activity index (AI) (IL-1β/IL-1RA) with velocity of tooth movement and growth status of individuals have also been deduced. A greater AI and RANKL/OPG ratio was seen in juveniles as compared to adults or non-growers that were associated with faster rate of OTM in juveniles. None of the studies addressed the effect of estrous cycle in female subjects. Lack of homogeneity in several parameters calls for a better controlled research on the biology of OTM.Electronic supplementary materialThe online version of this article (doi:10.1186/s40510-014-0065-6) contains supplementary material, which is available to authorized users.

Cytokines in crevicular fluid and orthodontic force: a systematic review

“…Light continuous force [30,31,42] tended to maintain longer, relatively high IL-1β levels, allowing a reduced frequency of re-activations [43]. These results reveal important clinical implications for orthodontics and provide evidence for the utilization of light continuous force in orthodontics at the cellular level [44], since light continuous forces induce relatively longer lasting levels of cytokines, which are necessary for continuous periodontal remodeling.…”

“…Common failures were observed in clinical and laboratory studies during selection of papers for inclusion. Concerning the cytokine levels in GCF over time, the most consistent results were peak levels of the different cytokines at one day after application of orthodontic force, regardless of the treatment mechanics [9,43].…”

“…Moreover, a heavy decaying force [27,34] tended to significantly decrease the IL-1β level at 7 d, suggesting the need for timely re-activation to keep sufficient IL-1β production [43]. Light continuous force [30,31,42] tended to maintain longer, relatively high IL-1β levels, allowing a reduced frequency of re-activations [43].…”

“…When mesial-distal movement forces were applied, most studies sampled GCF only at pressure sides; otherwise, no was associated with PGE 2 levels at 1 h, and with IL-1β levels at one day. Recently, Yamaguchi et al (27) reported significant correlation between IL-1β and substance P, which is a peptide involved in pain and neurotransmission, during orthodontic treatment in adults, indirectly supporting an association between pain and IL-1β levels [9,43].…”

The effect of mechanical vibration on orthodontically induced root resorption

“…6 Osteoprotegerin (OPG) and receptor activator of nuclear factor-kappaB ligand (RANKL) are paracrine regulators of osteoclastogenesis and cementoclastogenesis. [8][9][10] Among the many signals released in response to mechanical vibration, RANKL and OPG are regarded as two critical molecules regulating osteoclasts. 7,11,12 RANKL is expressed as a transmembrane protein in osteoblasts, whereas OPG is a protein secreted by the osteoblasts acting as a decoy receptor blocking the RANKL-RANK ligand interaction, thus antagonizing the formation of mature osteoclasts.…”