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

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.

[1]  S. Luppanapornlarp,et al.  Interleukin-1beta levels, pain intensity, and tooth movement using two different magnitudes of continuous orthodontic force. , 2010, European journal of orthodontics.

[2]  J. Nickel,et al.  Human interleukin-1 beta and interleukin-1 receptor antagonist secretion and velocity of tooth movement. , 2001, Archives of oral biology.

[3]  K. Balos,et al.  Levels of interleukin-8 during tooth movement. , 2005, The Angle orthodontist.

[4]  E. Rossomando,et al.  Orthodontic forces increase tumor necrosis factor alpha in the human gingival sulcus. , 1995, American journal of orthodontics and dentofacial orthopedics : official publication of the American Association of Orthodontists, its constituent societies, and the American Board of Orthodontics.

[5]  Sanghamitra Bandyopadhyay,et al.  Functional expression of beta-chemokine receptors in osteoblasts: role of regulated upon activation, normal T cell expressed and secreted (RANTES) in osteoblasts and regulation of its secretion by osteoblasts and osteoclasts. , 2005, Endocrinology.

[6]  Mette A. R. Kuijpers,et al.  Three-dimensional Imaging Methods for Quantitative Analysis of Facial Soft Tissues and Skeletal Morphology in Patients with Orofacial Clefts: A Systematic Review , 2014, PloS one.

[7]  J. Nickel,et al.  Speed of tooth movement is related to stress and IL-1 gene polymorphisms. , 2006, American journal of orthodontics and dentofacial orthopedics : official publication of the American Association of Orthodontists, its constituent societies, and the American Board of Orthodontics.

[8]  M. Yamaguchi,et al.  Relationship between substance P and interleukin-1beta in gingival crevicular fluid during orthodontic tooth movement in adults. , 2005, European journal of orthodontics.

[9]  T. Kawase,et al.  Cytokine secretion of periodontal ligament fibroblasts derived from human deciduous teeth: effect of mechanical stress on the secretion of transforming growth factor-beta 1 and macrophage colony stimulating factor. , 1999, Journal of periodontal research.

[10]  M. Serdar,et al.  Tumor Necrosis Factor–α Levels during Two Different Canine Distalization Techniques , 2007 .

[11]  M. Alikhani,et al.  Effect of micro-osteoperforations on the rate of tooth movement. , 2013, American journal of orthodontics and dentofacial orthopedics : official publication of the American Association of Orthodontists, its constituent societies, and the American Board of Orthodontics.

[12]  M. Bakhiet,et al.  Orthodontic tooth movement and de novo synthesis of proinflammatory cytokines. , 2001, American journal of orthodontics and dentofacial orthopedics : official publication of the American Association of Orthodontists, its constituent societies, and the American Board of Orthodontics.

[13]  Sarandeep S. Huja,et al.  Bone modeling: biomechanics, molecular mechanisms, and clinical perspectives , 2004 .

[14]  E. Uysal,et al.  Identification of tumor necrosis factor-α levels around miniscrews during canine distalization , 2011 .

[15]  T. Deguchi,et al.  Interleukin (IL)-1 beta, IL-6, tumor necrosis factor-alpha, epidermal growth factor, and beta 2-microglobulin levels are elevated in gingival crevicular fluid during human orthodontic tooth movement. , 1996, Journal of dental research.

[16]  W. Teughels,et al.  Longitudinal changes in gingival crevicular fluid after placement of fixed orthodontic appliances. , 2011, American journal of orthodontics and dentofacial orthopedics : official publication of the American Association of Orthodontists, its constituent societies, and the American Board of Orthodontics.

[17]  S. Théoleyre,et al.  The molecular triad OPG/RANK/RANKL: involvement in the orchestration of pathophysiological bone remodeling. , 2004, Cytokine & growth factor reviews.

[18]  M. Yamaguchi,et al.  Effects of aging on RANKL and OPG levels in gingival crevicular fluid during orthodontic tooth movement. , 2006, Orthodontics & craniofacial research.

[19]  Mariano Sanz,et al.  Biochemical markers of bone metabolism in gingival crevicular fluid during early orthodontic tooth movement. , 2013, The Angle orthodontist.

[20]  A. Meager.  Cytokine regulation of cellular adhesion molecule expression in inflammation. , 1999, Cytokine & growth factor reviews.

[21]  M. Chiba,et al.  Local RANKL gene transfer to the periodontal tissue accelerates orthodontic tooth movement , 2006, Gene Therapy.

[22]  Murray C Meikle,et al.  The tissue, cellular, and molecular regulation of orthodontic tooth movement: 100 years after Carl Sandstedt. , 2005, European journal of orthodontics.

[23]  L. Xing,et al.  Functions of RANKL/RANK/OPG in bone modeling and remodeling. , 2008, Archives of biochemistry and biophysics.

[24]  A. Vissink,et al.  Cytokines in crevicular fluid and orthodontic tooth movement. , 2008, European journal of oral sciences.

[25]  A. Kuijpers-Jagtman,et al.  Optimum force magnitude for orthodontic tooth movement: a systematic literature review. , 2009, The Angle orthodontist.

[26]  R. Masella,et al.  Current concepts in the biology of orthodontic tooth movement. , 2006, American journal of orthodontics and dentofacial orthopedics : official publication of the American Association of Orthodontists, its constituent societies, and the American Board of Orthodontics.

[27]  A. Çelebi,et al.  Effect of ovarian activity on orthodontic tooth movement and gingival crevicular fluid levels of interleukin-1β and prostaglandin E(2) in cats. , 2013, The Angle orthodontist.

[28]  T. Goto,et al.  Intermittent Force Induces High RANKL Expression in Human Periodontal Ligament Cells , 2007, Journal of dental research.

[29]  A. Kuijpers-Jagtman,et al.  Cytokine levels in crevicular fluid are less responsive to orthodontic force in adults than in juveniles. , 2002, Journal of clinical periodontology.

[30]  Cihan Uçar,et al.  Interleukin 1beta levels around microscrew implants during orthodontic tooth movement. , 2007, The Angle orthodontist.

[31]  R. Russell,et al.  An interleukin 1 like factor stimulates bone resorption in vitro , 1983, Nature.

[32]  E. Uysal,et al.  Identification of interleukin 2, 6, and 8 levels around miniscrews during orthodontic tooth movement. , 2012, European journal of orthodontics.

[33]  Vinod K Diwan,et al.  Design of a randomized trial to evaluate the influence of mobile phone reminders on adherence to first line antiretroviral treatment in South India - the HIVIND study protocol , 2010, BMC medical research methodology.

[34]  L. Chow,et al.  Comparative Evaluation of Cytokines in Gingival Crevicular Fluid and Saliva of Patients with Aggressive Periodontitis , 2013, The International journal of biological markers.

[35]  J. Nickel,et al.  Tooth movement and cytokines in gingival crevicular fluid and whole blood in growing and adult subjects. , 2005, American journal of orthodontics and dentofacial orthopedics : official publication of the American Association of Orthodontists, its constituent societies, and the American Board of Orthodontics.

[36]  S. Teitelbaum,et al.  Bone resorption by osteoclasts. , 2000, Science.

[37]  T. Deguchi,et al.  Increase of transforming growth factor-beta 1 in gingival crevicular fluid during human orthodontic tooth movement. , 1996, Archives of oral biology.

[38]  Peter Rock,et al.  Induction of cytokines, MMP9, TIMPs, RANKL and OPG during orthodontic tooth movement. , 2013, European journal of orthodontics.

[39]  Y. Nishijima,et al.  Levels of RANKL and OPG in gingival crevicular fluid during orthodontic tooth movement and effect of compression force on releases from periodontal ligament cells in vitro. , 2006, Orthodontics & craniofacial research.

[40]  Sanjay V. Ganeshkar,et al.  Comparison of the effects of ibuprofen and acetaminophen on PGE2 levels in the GCF during orthodontic tooth movement: a human study , 2013, Progress in Orthodontics.

[41]  J. Nickel,et al.  IL-1 gene polymorphisms, secretion in gingival crevicular fluid, and speed of human orthodontic tooth movement. , 2009, Orthodontics & craniofacial research.

[42]  E. Rossomando,et al.  Orthodontic forces increase tumor necrosis factor α in the human gingival sulcus , 1995 .

[43]  G. Wise,et al.  Mechanisms of Tooth Eruption and Orthodontic Tooth Movement , 2008, Journal of dental research.

[44]  G. K. Johnson,et al.  Prostaglandin E (PGE) and interleukin-1β (IL-1β) levels in gingival crevicular fluid during human orthodontic tooth movement , 1994 .

[45]  P. Ngan,et al.  Neurotransmitters, cytokines, and the control of alveolar bone remodeling in orthodontics. , 1988, Dental clinics of North America.

[46]  P. Collin‐Osdoby,et al.  CCR1 Chemokines Promote the Chemotactic Recruitment, RANKL Development, and Motility of Osteoclasts and Are Induced by Inflammatory Cytokines in Osteoblasts , 2004, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[47]  G. Başaran,et al.  TNF-α, IL-1β AND IL-8 LEVELS IN TOOTH EARLY LEVELLING MOVEMENT ORTHODONTIC TREATMENT , 2010 .

[48]  V. Uitto.  Gingival crevice fluid--an introduction. , 2003, Periodontology 2000.

[49]  Hideo Mitani,et al.  Periodontal Ligament Cells Under Mechanical Stress Induce Osteoclastogenesis by Receptor Activator of Nuclear Factor κB Ligand Up‐Regulation via Prostaglandin E2 Synthesis , 2002, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[50]  S. Kiliaridis,et al.  Composition changes in gingival crevicular fluid during orthodontic tooth movement: comparisons between tension and compression sides. , 2006, European journal of oral sciences.

[51]  Cihan Uçar,et al.  Interleukin 1β Levels around Microscrew Implants during Orthodontic Tooth Movement , 2007 .

[52]  H. Shimomura,et al.  Identification of marker proteins by orthodontic treatment: relationship of RANKL in the gingival crevicular fluid and of amylase in whole saliva with orthodontic treatment , 2013, Odontology.

[53]  Latife Arzu Aral,et al.  OPG-RANKL Levels After Continuous Orthodontic Force , 2013 .

[54]  G. Mundy.  Cytokines and local factors which affect osteoclast function. , 1992, International journal of cell cloning.

[55]  Società italiana di ortodonzia.  Progress in orthodontics , 2000 .

[56]  T. Ozer,et al.  Interleukins 2, 6, and 8 levels in human gingival sulcus during orthodontic treatment. , 2006, American journal of orthodontics and dentofacial orthopedics : official publication of the American Association of Orthodontists, its constituent societies, and the American Board of Orthodontics.

[57]  W. Leonard,et al.  Cytokine and Cytokine Receptor Pleiotropy and Redundancy* , 2002, The Journal of Biological Chemistry.

[58]  A. Kuijpers-Jagtman,et al.  Focal hyalinization during experimental tooth movement in beagle dogs. , 2004, American journal of orthodontics and dentofacial orthopedics : official publication of the American Association of Orthodontists, its constituent societies, and the American Board of Orthodontics.

[59]  M. Serdar,et al.  Tumor necrosis factor-alpha levels during two different canine distalization techniques. , 2007, The Angle orthodontist.

[60]  Seong-Ho Choi,et al.  Effects of continuous and interrupted orthodontic force on interleukin-1beta and prostaglandin E2 production in gingival crevicular fluid. , 2004, American journal of orthodontics and dentofacial orthopedics : official publication of the American Association of Orthodontists, its constituent societies, and the American Board of Orthodontics.

[61]  David L. Lacey,et al.  Osteoclast differentiation and activation , 2003, Nature.

[62]  T. Ozer,et al.  Interleukine-1beta and tumor necrosis factor-alpha levels in the human gingival sulcus during orthodontic treatment. , 2006, The Angle orthodontist.

[63]  Clara Gómez,et al.  Effects of low-level laser therapy on orthodontics: rate of tooth movement, pain, and release of RANKL and OPG in GCF , 2015, Lasers in Medical Science.

[64]  O. Kharbanda,et al.  A study of interleukin 1β levels in peri-miniscrew crevicular fluid (PMCF) , 2014, Progress in Orthodontics.

[65]  I. Lamster,et al.  Comparison of levels of inflammatory mediators IL-1beta and betaG in gingival crevicular fluid from molars, premolars, and incisors during rapid palatal expansion. , 2008, American journal of orthodontics and dentofacial orthopedics : official publication of the American Association of Orthodontists, its constituent societies, and the American Board of Orthodontics.

[66]  P. Bossuyt,et al.  BMC Medical Research Methodology , 2002 .

[67]  William A Wiltshire,et al.  Differences in the gingival crevicular fluid composition between adults and adolescents undergoing orthodontic treatment. , 2014, The Angle orthodontist.

[68]  M. Kriss,et al.  Human Microvascular Endothelial Cell Activation by IL‐1 and TNF‐α Stimulates the Adhesion and Transendothelial Migration of Circulating Human CD14+ Monocytes That Develop With RANKL Into Functional Osteoclasts , 2005, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[69]  B. Taşdelen,et al.  Osteoprotegerin in gingival crevicular fluid under long-term continuous orthodontic force application. , 2008, The Angle orthodontist.

[70]  S. Kiliaridis,et al.  Pain discomfort and crevicular fluid changes induced by orthodontic elastic separators in children. , 2006, The journal of pain : official journal of the American Pain Society.

[71]  Y. Liu,et al.  Cytokine Expression and Accelerated Tooth Movement , 2010, Journal of dental research.

[72]  M. Rashkova,et al.  Matrix Metalloproteinase-8 And Interleukin-1Β In Gingival Fluid Of Children In The First Three Months Of Orthodontic Treatment With Fixed Appliances , 2012, Folia medica.

[73]  I. Lamster,et al.  Interleukin-1β and β-Glucuronidase in gingival crevicular fluid from molars during rapid palatal expansion ☆ ☆☆ ★ , 1999 .

[74]  G. Başaran,et al.  Interleukine-1β and Tumor Necrosis Factor–α Levels in the Human Gingival Sulcus during Orthodontic Treatment , 2009 .

[75]  I. Ceylan,et al.  Evaluation of Oxidative Stress Biomarkers in Patients with Fixed Orthodontic Appliances , 2014, Disease markers.

[76]  A. Kuijpers-Jagtman,et al.  Incidence and severity of root resorption in orthodontically moved premolars in dogs. , 2004, Orthodontics & craniofacial research.

[77]  G. Karsenty.  The complexities of skeletal biology , 2003, Nature.

[78]  P. de Vos,et al.  Cytokine profiles in crevicular fluid during orthodontic tooth movement of short and long durations. , 2007, Journal of periodontology.

[79]  M. Chiba,et al.  Dual Regulation of Osteoclast Differentiation by Periodontal Ligament Cells through RANKL Stimulation and OPG Inhibition , 2001, Journal of dental research.

[80]  P. Ngan,et al.  Effects of cytokines on prostaglandin E and cAMP levels in human periodontal ligament fibroblasts in vitro. , 1990, Archives of oral biology.

[81]  Jonas Capelli,et al.  Matrix metalloproteinases and chemokines in the gingival crevicular fluid during orthodontic tooth movement. , 2011, European journal of orthodontics.

[82]  Y. Shibasaki,et al.  Osteoclast induction in periodontal tissue during experimental movement of incisors in osteoprotegerin‐deficient mice , 2002, The Anatomical record.

[83]  T. Aydın,et al.  Leptin levels in gingival crevicular fluid during orthodontic tooth movement. , 2010, The Angle orthodontist.