ORIGINAL RESEARCH |
https://doi.org/10.5005/jp-journals-10015-2564 |
Comparison of Caffeine and Ethanol Administration on Receptor Activator of Nuclear Factor Kappa-β and Osteoprotegerin Expression in Orthodontic Tooth Movement
1–5Department of Orthodontics, Faculty of Dentistry, Hasanuddin University, Makassar, Indonesia
Corresponding Author: Ardiansyah Sahabu Pawinru, Department of Orthodontics, Faculty of Dentistry, Hasanuddin University, Makassar, Indonesia, Phone: +62 81342266388, e-mail: ardiansyah.pawinru@unhas.ac.id
Received: 12 December 2024; Accepted: 27 January 2025; Published on: 13 March 2025
ABSTRACT
Aim: This study aims to assess the impact of caffeine and ethanol on the expression of receptor activator of nuclear factor kappa-β (RANK) and osteoprotegerin (OPG), in addition to tooth mobility during orthodontic therapy.
Materials and methods: The study was executed experimentally in the laboratory utilizing a posttest only control group strategy. The sample comprised 15 Wistar rats equipped with a closed coil spring, categorized into three groups: the orthodontic force group, the orthodontic force and caffeine group, and the orthodontic force and ethanol group, each observed for 3 days. Tooth movement was assessed on day 3, after which the rats were euthanized and specimens were prepared utilizing immunohistochemistry (IHC).
Results: The expression of RANK on day 3 seems to elevate with the administration of force combined with caffeine; however, it does not differ significantly when only force is delivered. The application of force combined with ethanol in orthodontic tooth movement (OTM) influences RANK expression; however, it does not significantly differ from the absence of ethanol during the process. The expression of OPG on day 3, as presented in Tables 1 and 2, demonstrates that group (N2) has a larger OPG expression than group (N1), with statistically significant differences. Caffeine concentration can elevate OPG expression in osteoblasts, thereby influencing bone apposition during orthodontic therapy. The expression of OPG in each group indicates that the force + ethanol treatment (N3) does not exceed the force + caffeine treatment (N2). The administration of both force combined with caffeine and force combined with ethanol similarly affects RANK expression and elevates osteoclast numbers in the presence of receptor activator of nuclear factor-κB-ligand (RANKL), a regulator of bone remodeling during tooth movement.
Conclusion: Caffeine and ethanol affect the elevated expression of OPG and RANK. The comparison of their impact on the expression of OPG and RANK is not significantly different following the application of orthodontic force on day 3.
Clinical Significance: This study highlights the clinical implications of caffeine and ethanol in modulating RANK and OPG expression during OTM. This understanding could inform the development of more targeted orthodontic interventions. Ultimately, these findings may enhance therapeutic strategies for managing OTM and improve patient outcomes.
Keywords: Bone remodeling, Caffeine, Ethanol, Orthodontic tooth movement, Osteoprotegerin, Receptor activator of nuclear factor kappa-β
How to cite this article: Pawinru AS, Erwansyah E, Habar EH, et al. Comparison of Caffeine and Ethanol Administration on Receptor Activator of Nuclear Factor Kappa-β and Osteoprotegerin Expression in Orthodontic Tooth Movement. World J Dent 2025;16(1):1–7.
Source of support: Nil
Conflict of interest: None
INTRODUCTION
Coffee and alcohol receptor activator of nuclear factor kappa-β (RANK) among the most favored beverages globally, including in Indonesia. Knapik et al. estimate that the prevalence of caffeine use among adults is 89%.1 According to World Health Organization (WHO) in 2018, alcohol use in Southeast Asia has increased. Caffeine and ethanol will undoubtedly alter orthodontic treatment, particularly during the orthodontic tooth movement (OTM) procedure.
There are two types of coffee commonly consumed by the public: Arabica and Robusta. According to Kristiyanto et al., Robusta coffee has a higher caffeine content, at 2.4%, compared to the caffeine content in Arabica coffee, which is 1.9%.2 Arabica coffee contains bioactive antioxidant compounds that are beneficial for health, such as polyphenols, flavonoids, proanthocyanidins, coumarins, chlorogenic acids, trigonelline, tocopherols, cafestol, and kahweol. It also has a more preferred aroma compared to Robusta.3
The administration of caffeine during orthodontic treatment has been demonstrated to enhance tooth mobility. Herniyati et al. discovered in their study that the administration of caffeine elevated the expression of receptor activator of nuclear factor-κB-ligand (RANKL) and osteoclasts during orthodontic movement.4 Consistent with the findings of Herniyati et al., Golshah et al. similarly discovered that caffeine injections in rats receiving orthodontic therapy markedly enhanced orthodontic tooth mobility.5 Berman et al. indicate that high-dose consumption of caffeine may impact bone density, potentially affecting orthodontic tooth mobility.6
On the contrary, per capita alcohol consumption is projected to increase in half of the Asian region by 2025. The WHO in 2018 said that the highest increase is expected in Southeast Asia, with an increase of 2.2 L in India, representing the largest population. An increase is also expected in Indonesia and Thailand, representing the second and fourth largest populations, respectively. In Indonesia, the proportion of alcohol consumption among the population over 10 years old is 3.3%, with five provinces having the highest consumption rates above 10%: North Sulawesi, East Nusa Tenggara (NTT), Bali, Gorontalo, and Maluku.7,8
Alcoholic beverages have become an integral part of the long journey of human civilization. In Indonesia, many traditional beverages such as tuak, arak, sopi, badeg, and others are widely found and consumed by people for reasons of tradition or custom. The presence of alcoholic beverages at traditional festive celebrations, especially in Indonesia, is due to traditions that originated from the ancestors of the communities in certain areas, and some people consider alcoholic beverages as a drink of honor. One region in South Sulawesi Province that still maintains the tradition of consuming alcoholic beverages is North Toraja Regency.
Conversely, Araujo asserts that ethanol induces an imbalance in the processes of bone production and resorption, which can ultimately impact bone apposition directly.7,9 Schröder elucidates that ethanol can directly affect the stimulation of osteoclasts and osteogenesis, hence suppressing preosteoblast indicators.10
Orthodontic tooth movement necessitates the synchronized activity of various cell types in alveolar bone remodeling, including periodontal ligament (PDL) fibroblasts, mesenchymal stem cells, inflammatory cells, osteoblasts, osteocytes, and osteoclasts.11 These cell types generate synchronized cellular activity resulting in bone resorption executed by osteoclasts, succeeded by bone synthesis conducted by osteoblasts.12 In the pressure area, the inflammatory response stimulates macrophages to generate proinflammatory cytokines, including interleukin-6 (IL-6), tumor necrosis factor (TNF), granulocyte and macrophage colony stimulating factor (M-CSF), and chiefly interleukin-1 (IL-1). These cytokines activate preosteoclasts, resulting in the formation of osteoclasts that facilitate the resorption of alveolar bone. In the tension zone, the pull induces an anti-inflammatory response, releasing cytokines and growth factors such as IL-6, IL-10, transforming growth factor beta (TGF-β), and osteoprotegerin (OPG), which promote the development of osteoblasts, leading to bone apposition. The processes of resorption and apposition are referred to as the bone remodeling phase, which facilitates tooth mobility.11
Proinflammatory cytokines, including IL-1, are generated by mononuclear phagocytes and serve as the principal cytokines involved in OTM by stimulating osteoclast formation. IL-1 is a principal stimulator of the secretion of additional proinflammatory cytokines, including RANK. RANK is released by mature osteoclasts. The RANK function is activated upon binding with RANKL, resulting in bone resorption on the pressure side. Conversely, RANKL can associate with OPG, a natural inhibitor that obstructs the interaction between RANKL and RANK. OPG that binds to RANKL will impede the proliferation and differentiation of osteoclasts, thereby decelerating bone resorption.13 Therefore, the author aims to investigate the comparative effects of coffee and ethanol on the expression of RANK and OPG during OTM.
MATERIALS AND METHODS
The ethical approval for this animal study has been granted by the Ethics and Advocacy Unit of the Faculty of Medicine, Hasanuddin University, under recommendation number 420/UN4.6.4.5.31/PP36/2023.
Each treatment group consists of five rats in the treatment group and five rats in the control group.
Inclusion Criteria
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Healthy condition of the rats.
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No visible anatomical abnormalities.
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Body weight of 200–250 gm.
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Male gender.
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Age of the rats 2–3 months.
Exclusion Criteria
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Absence of incisors and molars in the rats.
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Weight loss.
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Behavioral changes (loss of appetite and lethargy).
Installation of Closed Coil Spring
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Before the procedure of installation and activation of the Nickel–Titanium (Ni–Ti) closed coil spring, intramuscular injection of ketamine anesthesia is administered. The Ni–Ti closed coil spring is then installed on one side with fixation using 0.1 stainless steel ligature wire.
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The force magnitude is then measured using a tension gauge to achieve a force of 50 gm/cm².
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Once the desired force magnitude is obtained, the closed coil spring is fixed on the opposite side using 0.1 stainless steel ligature wire.
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To enhance retention, flowable composite is applied.
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After installing the Ni–Ti closed coil spring on the same day, caffeine and ethanol, as well as a combination of caffeine and ethanol, are administered to the test animals.
Caffeine from Arabica coffee is administered orally to the test rats using a probe with a solution volume of 5 mg/mL coffee extract every day.
Ethanol is administered to the test rats using a probe, with the volume of the administered solution being 2.06 mL/kg body weight × 0.25 kg of the test animal’s mass, which is 0.515 mL each day.
Preparation procedure on day 3 involves decapitation of the rats for each treatment. Before decapitation, the rats are given an injection of ketamine 160 mg/kg body weight, administered intramuscularly in the upper thigh. The rats are decapitated using cervical dislocation (thumb and index finger placed on either side of the neck at the base of the skull, while the other hand pulls the tail or hind legs to separate the cervical part from the skull). The maxilla, including the incisors, is taken and immersed in a solution for lysis and fixation for 24 hours. Fixation is done by placing the extracted bone tissue in 10% formalin (pH 7.0) to preserve the tissue structure. Then, embedding, coating of the glass object, and drying of the tissue preparation are performed.
Observation with immunohistochemistry (IHC) staining is done in three fields of view in the pressure and tension areas, namely in the cervical third, middle third, and apical third. Each slide has three expression counts, which are then summed and divided by three to obtain the average expression number for each slide.
The primary data analysis of RANK and OPG is first tested for normality using the Kolmogorov–Smirnov test.
The animals were acclimatized for 1 week before treatment to adjust to their housing and diet. About 15 Wistar rats were acclimatized and categorized into three groups: N1 (force group), N2 (force + caffeine group), and N3 (force + ethanol group). Each group was monitored over a 3-day intervention period. All test subjects had an intramuscular injection of anesthetic (ketamine) prior to the placement of the Ni–Ti closed coil spring on one side, secured with 0.1 stainless steel ligature wire and the application of flowable composite. The force was subsequently quantified with a tension gauge, yielding a measurement of 50 gm/cm². Upon achieving the requisite force, the closed coil spring was secured on the opposing side using 0.1 stainless steel ligature wire, as shown in Figure 1.
Fig. 1: A specifically engineered fixation apparatus for orthodontic procedures in rats. The 0.25 N Ni–Ti coil spring is bisected (inset: supplementary wire put into the coil spring’s end) between the first upper left molar and the upper incisors for mobilization
The tissue was prepared by staining it with IHC. Observations were conducted in three fields of view within the pressure and tension regions: the cervical third, middle third, and apical third. Each slide contained three measurements of expression levels, which were subsequently totaled and divided by three to calculate the average expression level for each slide. The summary of the methodological steps can be seen in Figures 234.
Fig. 2: Immunohistochemical analysis illustrating the impact of caffeine on the expression levels of RANK and OPG on day 3 within the pressure area, utilizing magnifications of 400× and 1000×. The image captured at 400× magnification reveals the position and quantity of biomarkers, whereas the 1000× magnification illustrates the morphology of biomarkers through the application of the IHC technique
Fig. 3: Immunohistochemical analysis illustrating the impact of ethanol on the expression levels of RANK and OPG on day 3 within the pressure area, observed at magnifications of 400× and 1000×. The black box image at 400× magnification illustrates the location and quantity of biomarkers, whereas the 1000× magnification reveals the morphology of biomarkers through the IHC technique
Fig. 4: Summary of the methodological steps
The evaluation of RANK and OPG expression was performed using the ImmunoRatio (IRS) tool, whereas the assessment of OTM was conducted on the sample groups on day 3. Data were gathered and analyzed utilizing SPSS software. The normalcy of RANK and OPG expression was initially assessed using the Kolmogorov–Smirnov test. If the normality test result was above 0.05, the data were deemed normally distributed and further analyzed using a parametric test, namely the independent sample t-test, to assess the effects and differences in RANK and OPG expression.
RESULTS
The study aimed to compare the impacts of ethanol and caffeine on the biomarkers RANK and OPG, utilizing samples from 15 rats. The subjects were categorized into three distinct groups, with each group comprising five rats.
Table 1 presents a detailed overview of the average levels of the biomarkers RANK and OPG measured on day 3. The data presented in this table indicate a rise in the average expression levels of RANK and OPG. This demonstrates that a process occurs involving the release of proinflammatory and anti-inflammatory cytokines during orthodontic treatment, with notable differences observed among the various treatment groups.
| Treatment | Biomarker | Day-3 (mean ± SD) |
|---|---|---|
| Force (N1) | Rank | 8.00 ± 2.23 |
| OPG | 6.20 ± 1.48 | |
| Force + caffeine (N2) | Rank | 8.40 ± 1.14 |
| OPG | 8.20 ± 0.83 |
*Significant with paired t-test (p < 0.05)
The findings from the immunohistochemical observations regarding the impact of caffeine on RANK and OPG were obtained through a light microscope (Leica ICC50W) at magnifications of 400× and 1000×, as shown in Figure 2.
Table 2 illustrates the impact of caffeine on the expression levels of RANK and OPG when comparing group N1 (force) to group N2 (force + caffeine) on day 3. The findings from the statistical analysis utilizing the independent sample t-test reveal a notable difference in OPG on day 3, suggesting that the administration of caffeine to rats enhances OPG expression on day 3 (p < 0.05). Nonetheless, the expression of RANK on day 3 demonstrates no significant difference (p > 0.05), indicating that the administration of caffeine to rats does not lead to a notable change in RANK expression on day 3.
| Group | Day-3 | |
|---|---|---|
| RANK mean ± SD | OPG mean ± SD | |
| N1 (force) | 8.00 ± 2.236 | 6.20 ± 1.483 |
| N2 (force + caffeine) | 8.40 ± 1.140 | 8.20 ± 0.837 |
| P | 0.731 | 0.030* |
*Significant with paired t-test (p < 0.05)
The findings from the immunohistochemical observations regarding the impact of ethanol on RANK and OPG were obtained using a light microscope (Leica ICC50W) at magnifications of 400× and 1000×, shown in Figure 3.
The immunohistochemical analysis reveals that the expression levels of RANK and OPG in the pressure area at 400× and 1000× magnification exhibit alterations on day 3.
Table 3 illustrates the impact of ethanol on the expression of RANK and OPG between group N1 (force) and group N3 (force + ethanol) on day 3. The expression of RANK on day 3 demonstrates no significant difference (p > 0.05), and similarly, the expression of OPG on day 3 shows no significant difference (p > 0.05), demonstrating that ethanol treatment to rats does not induce a substantial alteration in the expression of RANK and OPG on day 3.
| Group | Day-3 | |
|---|---|---|
| RANK mean ± SD | OPG mean ± SD | |
| N1 (force) | 8.00 ± 2.236 | 6.20 ± 1.483 |
| N3 (force + ethanol) | 8.80 ± 2.588 | 8.20 ± 1.643 |
| P | 0.615 | 0.078 |
*Significant with paired t-test (p < 0.05)
Table 4 presents a comparison of rank expression across each treatment group on day 3. The statistical analysis employing the independent sample t-test reveals that the mean expression of rank in group N2, when compared to group N3 (p < 0.05) on day 3, does not exhibit a significant difference, indicating that the administration of ethanol and caffeine to rats does not produce a substantial alteration in rank expression on day 3.
| Group | Day-3 | |
|---|---|---|
| (Mean ± SD) | p-value | |
| Force + caffeine (N2) | 8.40 ± 1.140 | 0.731 |
| Force + ethanol (N3) | 8.80 ± 2.588 | 0.615 |
*Significant with paired t-test (p < 0.05)
Table 5 shows the comparison of OPG expression in each treatment group on day 3. The results of the statistical test using the independent sample t-test indicate a significant difference in the mean OPG expression between group N1 and group N2 on day 3 (p < 0.05), meaning that the administration of force + caffeine has the most impact on the increase in OPG expression on day 3.
| Group | Day-3 | |
|---|---|---|
| (Mean ± SD) | p-value | |
| Force + caffeine (N2) | 8.20 ± 0.837 | 0.030* |
| Force + ethanol (N3) | 8.20 ± 1.643 | 0.078 |
*Significant with paired t-test (p < 0.05)
DISCUSSION
This study was conducted to examine the relationship between ethanol and caffeine administration and the resulting OTM. RANKL is a cytokine that affects osteoblast formation. RANKL bound to RANK will prevent the differentiation of osteoblasts.14
On day 3, the expression of RANK, as presented in Table 1, indicates that the force + caffeine group (N2) exhibits a greater RANK expression compared to the force group (N1), but this difference is not statistically significant, with a p-value exceeding 0.05. The expression of RANK seems to elevate with the combination of force and caffeine therapy; nevertheless, it does not differ significantly from the application of force alone.
This condition results from caffeine’s promotion of osteoclastogenesis, as indicated by a study conducted by Yi et al., which asserts that caffeine treatment amplifies osteoclastogenesis triggered by PDL cells. Osteoclasts are multinucleated cells generated by the fusing of mononuclear precursors derived from the hematopoietic lineage.15 The differentiation of osteoclasts primarily relies on signals via c-fms, a receptor for M-CSF, in mononuclear precursor cells, which modulates RANK expression. RANKL regulates osteoclast production and activation, influenced by several hormones and cytokines that interact with RANKL, which then binds to the RANK receptor on osteoclasts. This binding facilitates the swift development of osteoclast precursors into mature, bone-resorbing osteoclasts.
The development and activation of osteoclasts are influenced by the transcription factor nuclear factor of activated T-cells cytoplasmic 1 (NFATC1). NFATC1 is the principal regulator of RANKL-induced osteoclast differentiation and is essential for osteoclast fusion and activation by upregulating numerous genes involved in osteoclast attachment, migration, acidification, and the degradation of both inorganic and organic components of the bone matrix.16 The interaction of RANKL with its receptor RANK activates various signaling pathways facilitated by c-Jun N-terminal kinase (JNK), p38, and extracellular signal-regulated kinase (ERK) MAP kinase in preosteoclasts. The activation of p38 MAP kinase is crucial for RANKL-induced osteoclast development, since it governs the expression of several osteoclast-associated genes. The activation leads to the stimulation of the microphthalmia-associated transcription factor (Mitf/MITF), which regulates the production of genes for tartrate-resistant acid phosphatase (TRAP, encoded by Acp5) and cathepsin K (CtsK). TRAP, an indicator of osteoclast development, along with CtsK, also affects the functional activity of osteoclasts by modulating bone matrix resorption and collagen turnover.17
The application of force combined with ethanol in OTM influences RANK expression; nevertheless, it does not differ significantly from the impact of OTM absent ethanol administration. This aligns with the findings of Iitsuka et al., which indicated that ethanol enhances both the activity and quantity of osteoclasts, hence promoting osteoclastogenesis alongside an increase in RANK.18 This disorder results from the influence of ethanol on bone metabolism. Ethanol additionally influences the enhancement of osteoclastogenesis.16,18
The research by Von Böhl indicated that alveolar bone remodeling during OTM necessitates the coordinated activity of multiple cell types, including PDL fibroblasts, mesenchymal stem cells, inflammatory cells, osteoblasts, osteocytes, and osteoclasts. OTM typically comprises three phases on the compression side: (1) gradual compression of the PDL, lasting approximately 4–7 days, (2) the hyalinization phase, characterized by cellular necrosis due to insufficient blood supply in the PDL compression region, which may extend for 7–14 days or longer, and (3) the secondary phase, distinguished by direct bone resorption, facilitating continued tooth movement.19,21
Osteoprotegerin functions as a crucial regulator against osteoclastogenesis by acting as the RANKL.21,23 On day 3, the expression of OPG (p = 0.030), as indicated in Table 2, demonstrates that group (N2) exhibits a larger OPG expression compared to group (N1), with statistically significant differences. Caffeine concentration can elevate OPG expression in osteoblasts, hence influencing bone apposition during orthodontic therapy.
The study by Holland et al. demonstrated that the administration of orthodontic force in rats initiated preosteoblast growth by the second day of force application.23 This, however, conflicts with the research conducted by Liu et al. Liu et al.’s research indicates that bone remodeling involves a synergistic relationship between resorption and deposition, which is crucial for maintaining bone homeostasis. Numerous variables influence bone remodeling, including prostaglandins (PGs), 1,25-dihydroxyvitamin D3, parathyroid hormone (PTH), nitric oxide, sex hormones, calcitonin, growth factors, and cytokines.24
Bone resorption resulting from osteoclastogenesis entails critical molecules like RANKL, RANK, and OPG. RANKL, produced by osteoblasts, binds to RANK, a receptor for RANKL found on osteoclast progenitors; this contact promotes the development of osteoclast progenitors into mature osteoclasts in the presence of M-CSF. OPG, synthesized by osteoblasts, functions as a decoy receptor for RANKL, hence inhibiting osteoclastogenesis by interfering with the RANK–RANKL interaction. The increase of cyclooxygenase-2 (COX-2) expression and the availability of arachidonic acid substrate are necessary for osteoblasts to stimulate prostaglandin synthesis. PGs can augment osteoclastogenesis by elevating RANKL expression in osteoblasts.24
Okada et al. revealed that COX-2 protein expression and associated PG synthesis are essential for the bone resorption response to 1,25(OH)2D3 and PTH. The production of PGE2, mediated by COX-2, is essential for bone resorption induced by lipopolysaccharide (bacterial endotoxin). Bradykinin enhances cytokine-induced prostaglandin synthesis in osteoblasts via elevating COX-2 expression, which leads to enhanced RANKL expression. Compressive force promotes osteoclast development by increasing RANKL expression and M-CSF synthesis, while decreasing OPG production via the COX-2/PGE2 pathway in osteoblasts.25
Liu et al. discovered that low caffeine concentrations elevate RANKL protein expression in cultured MC3T3-E1 osteoblastic cells and newborn rat calvariae, concurrently diminishing OPG expression in osteoblasts.24
The expression of OPG in each group indicates that the force + ethanol treatment (N3) does not exceed the force + caffeine treatment (N2). The application of force combined with ethanol induces a modest expression of OPG in the bone remodeling process during OTM. This aligns with the study by Naghsh et al., which highlights the significance of this mechanism in bone remodeling, especially for the interplay among OPG, RANK, and RANKL. OPG, a soluble glycoprotein, functions as a TNF alpha that engages target cells by binding to RANKL, thereby obstructing the RANK–RANKL connection and suppressing osteoclastogenesis.26 This corroborates the findings of Belibasakis and Capati MLF, which indicate an inverse relationship between OPG and RANKL; a decrease in OPG expression results in an increase in RANKL expression.27 OPG binds to RANKL, preventing its interaction with RANK, which consequently reduces osteoclastogenesis, osteoclast activity, and bone resorption. Osteoblasts regulate osteoclast development and activity in the remodeling process by influencing the interaction between RANKL and OPG.27
Caffeine in coffee dramatically elevates OPG levels due to the presence of both caffeine and caffeic acid, a nonphenolic flavonoid acid. Caffeic acid functions as an antioxidant that mitigates oxidative stress in osteoblasts. Numerous in vitro and in vivo animal studies have demonstrated that oxidative stress diminishes the pace of bone formation by impairing osteoblast development and longevity.28,29
The application of force combined with caffeine and force combined with ethanol both similarly influence RANK expression and elevate osteoclast numbers. RANKL, a regulator of bone remodeling during tooth movement, binds to RANK on osteoclast precursors, initiating their differentiation and proliferation, hence activating osteoclasts. Active osteoclasts result in heightened bone resorption.30 The research conducted by Roodman demonstrates that osteoclastogenesis is crucial in orthodontic tooth mobility.31
The application of force combined with caffeine and force combined with ethanol yields comparable effects on OPG expression on the 3rd day of OTM. Despite the continued elevation in OPG expression levels from day 3, this phenomenon occurs because osteoblasts produce OPG, which obstructs the binding of RANK to RANKL, as elucidated in Baloul’s study.32 This inhibits osteoclast differentiation, hastens osteoclast apoptosis, and ultimately diminishes osteoclast activity. Elevated OPG levels synthesized by osteoblasts result in diminished RANKL levels. Ethanol and caffeine influence the expression of RANK and OPG, thereby potentially aiding OTM.
CONCLUSION
Caffeine and ethanol influence the increased expression of OPG and RANK. The comparison of their effects on the expression of OPG and RANK is not significantly different after the application of orthodontic force on day 3. The increase in OPG expression on the third day will lead to an increase in osteoblasts, which accelerates bone apposition during the tooth movement process.
Clinical Significance
This study highlights the clinical implications of caffeine and ethanol in modulating RANK and OPG expression during OTM. The results indicate that both substances similarly influence these biomarkers, providing valuable insights into the biochemical pathways of bone remodeling. This understanding could inform the development of more targeted orthodontic interventions. Ultimately, these findings may enhance therapeutic strategies for managing OTM and improve patient outcomes.
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