Translate this page into:
Effect of 10% Trigona sp. propolis gel on osteoclasts, osteoblasts, and receptor activator of nuclear factor KB ligand expression during bone remodeling around temporary anchorage devices: An in vivo stud y
, Baharuddin M. Ranggang1,, Eddy Heriyanto Habar1, Eka Erwansyah1, Ardiansyah S. Pawinru1, Donald R. Nahusona1, Zilal I. Paramma1
-
Received: ,
Accepted: ,
How to cite this article: Abdullah F, Ranggang BM, Habar EH, Erwansyah E, Pawinru AS, Nahusona DR, et al. Effect of 10% Trigona sp. propolis gel on osteoclasts, osteoblasts, and receptor activator of nuclear factor KB ligand expression during bone remodeling around temporary anchorage devices: An in vivo study. APOS Trends Orthod. doi: 10.25259/APOS_199_2025
Abstract
Objectives:
To evaluate the effect of 10% Trigona sp. propolis gel on osteoclasts, osteoblasts, and RANKL expression during bone remodeling around temporary anchorage devices.
Material and Methods:
Thirty male rabbits were randomly divided into six groups (n = 5/group), comprising control and treatment groups observed on days 3, 7, and 14 after TAD placement. The treatment group received topical 10% Trigona sp. propolis gel twice daily (0.5 g per application) around the TAD site. Osteoblasts and osteoclasts were quantified histologically using hematoxylin-eosin staining, and RANKL expression was measured using ELISA. Data were analyzed using independent t-tests and linear regression (p < 0.05).
Results:
Propolis treatment significantly reduced osteoclast counts and increased osteoblast numbers at all observation points (p < 0.05). On day 14, osteoclasts were reduced to 0.80 ± 1.10, while osteoblasts increased to 296.00 ± 24.17 (p = 0.001). Linear regression analysis revealed strong correlations between treatment duration and both osteoblast (R2 = 0.935) and osteoclast (R2 = 0.859) counts. Although RANKL expression showed no significant difference on day 14 (p = 0.421), it declined over time (R2 = 0.530, p = 0.001), indicating time-dependent modulation.
Conclusion:
These findings indicate that 10% Trigona sp. propolis gel has the potential to enhance peri-implant bone remodeling and biological healing responses around TADs, suggestsing its potential as a local adjunctive agent in orthodontic applications.
Keywords
Bone remodeling
Osteoblast
Osteoclast
Propolis
Temporary anchorage device
INTRODUCTION
Temporary anchorage devices (TADs) are widely utilized in orthodontic treatment to facilitate complex tooth movements, including intrusion, en masse retraction, uprighting, and distalization, which are often unattainable to achieve with conventional anchorage systems. The success of micro implant anchorage is determined by factors such as implant design, precise placement, and appropriate surgical techniques. When these factors are optimized, TADs provide reliable and stable anchorage independent of patient compliance. Effective anchorage control is essential to prevent undesirable tooth movement resulting from orthodontic reaction forces and is further influenced by biomechanical factors, including root morphology, periodontal support, the type and magnitude of tooth movement, and treatment duration.[1,2]
Orthodontic mini-implants, or TADs revolutionize orthodontic biomechanics by establishing absolute anchorage.[3] These devices typically consist of four components: A screw head for auxiliary attachment, a transgingival neck traversing the soft tissue, a threaded body that engages the bone, and a self-drilling tip that allows placement without pre-drilling.[4] This design enables precise force application and minimizes unwanted reciprocal tooth movement, contributing to their widespread acceptance.[5]
Despite their advantages, TAD insertion induces microtrauma in the surrounding bone, triggering an inflammatory response followed by a cascade of bone remodeling. Bone remodeling is a highly regulated process involving osteoclast (resorption) and osteoblast (apposition). A balanced interaction between these two cell types is essential for maintaining bone homeostasis and determining long-term implant stability.[6,7] Accelerated bone healing around the TAD is desirable because early bone loss or delayed remodeling may compromise mechanical retention and increase the risk of failure.[6]
The receptor activator of nuclear factor KB ligand (RANK)-RANKL-osteoprotegerin (OPG) pathway serves as the master regulator of osteoclast differentiation and activation. Receptor activator of nuclear factor KB ligand (RANKL), produced by osteoblast and stromal cells, binds to RANK on osteoclast precursors and is upregulated during the early inflammatory phase following mechanical or surgical insult.[8,9] Thus, RANKL functions as a significant molecular biomarker reflecting the rate of early bone turnover.
Propolis, produced by bees, contains bioactive compounds including flavonoids and phenolic acids known for their anti-inflammatory, antioxidant, and regenerative properties.[10] Several in vivo studies demonstrate that propolis enhances osteoblast differentiation, reduces osteoclast activity, and promotes bone formation in various bone-injury models.[11,12] However, its role in peri-implant bone healing around orthodontic TADs has not been reported. Existing studies focus on fractures, extraction sockets, or graft sites, leaving a gap in evidence of propolis enhancing TAD stability.
Therefore, this study aims to evaluate the effect of 10% Trigona sp. propolis gel on osteoblast and osteoclast counts and on RANKL expression during bone remodeling following TAD placement. The central investigation is to determine whether propolis can serve as a local adjunctive agent to enhance peri-implant bone healing and improve the biological stability of TADs.
MATERIAL AND METHODS
Study design and ethical approval
This study utilized a post-test-only control group design for an in vivo experimental investigation. Ethical approval was obtained from the Ethics Committee of the Dental Hospital, Hasanuddin University (Approval No. 091/KEPK FKGRSGMP UH/EA/III/2025).
Animal subjects
Thirty healthy male New Zealand white rabbits (Oryctolagus cuniculus), aged 4–6 months and weighing between 1.5 and 2.0 kg, were used. All animals were acclimatized for 1 week and housed individually with ad libitum access to food and water. The study was conducted at the Animal Hospital, Faculty of Veterinary Medicine, Hasanuddin University, Indonesia.
Sample allocation
Animals were randomly divided into a control group (no treatment) and a treatment group (topical 10% propolis gel), subdivided based on three observations (Days 3, 7, and 14), with five rabbits in each subgroup. Inclusion criteria were (1) healthy; (2) no anatomical abnormalities; (3) body weight of 1.5–2.0 kg; (4) male; and (5) age between 4 and 6 months. Exclusion criteria included (1) signs of illness or deformity and (2) early TAD dislodgment before the observation endpoint. During the experiment, no animals or data points were excluded, because rabbits remained healthy and TADs remained stable until the designated observation days.
Preparation of 10% propolis gel
Pure propolis was obtained from Trigona bees, from a breeding center at the Faculty of Forestry, Hasanuddin University. The propolis was extracted through maceration in ethanol and formulated into a 10% w/v gel using carboxymethyl cellulose (CMC) as a base at the Faculty of Pharmacy Laboratory, Hasanuddin University [Figure 1]. Gel (0.5 g) was applied twice daily to the peri-implant region using a sterile cotton bud during the observation period.
TAD insertion procedure
Under general anesthesia (ketamine 35 mg/kg and xylazine 5 mg/kg intramuscularly), TADs were placed in the anterior maxillary alveolar bone. No pre-drilling was performed [Figure 2].
Histological examination
At the end of each experimental time point, rabbits were euthanized by intracardiac injection of ketamine. The maxillary bone surrounding the TAD was excised as a 1 × 1 cm peri-implant specimen immediately adjacent to the TAD threads, including both resorptive and formative bone surfaces. The specimens were fixed in 10% buffered formalin, decalcified, embedded in paraffin, and sectioned. Histological sections were stained with hematoxylin and eosin (H and E) and examined under a light microscope. Osteoblast and osteoclast numbers were quantified in 10 randomly selected high-power fields at ×400 magnification, and the mean value was used for statistical analysis.
Histological evaluations were independently performed by two blinded and calibrated observers, with discrepancies resolved by consensus. All histological procedures were conducted at the Anatomical Pathology Laboratory, Hasanuddin University Teaching Hospital.
RANKL expression analysis
Blood samples were collected from the central ear artery and analyzed for RANKL using an enzyme-linked immunosorbent assay (ELISA) with a Rabbit RANKL ELISA Kit (Reed Biotech, USA; Cat. No. MBGAM0002, Lot: M170425E6, Exp: 2026-05-16), in accordance with the manufacturer’s protocol. After incubation with HRPconjugated antibodies and substrate solution, absorbance was measured at 450 nm. RANKL concentrations were expressed in ng/mL. All assays were performed at Hasanuddin University Teaching Hospital.
Statistical analysis
Quantitative data were analyzed using Statistical Package for the Social Sciences version 25. Independent t-tests were applied to compare the control and treatment groups at each time point (Days 3, 7, and 14). Linear regression analysis was performed to evaluate the time-dependent effects of propolis application. Statistical significance was established at p < 0.05.
RESULTS
Histological findings
Histological appearance of bone tissue at the TAD site on Day 3 (H and E staining, ×400 magnification). (A) Control group; (B) Propolis-treated group. Osteoclasts (red boxes) are large, multinucleated cells attached to resorptive bone surfaces. Osteoblasts (black boxes) appear as cuboidal cells aligned along newly forming bone. On Day 3 [Figure 3], histological sections demonstrated active cellular remodeling at the TAD interface. In the control group [Figure 3a], osteoclasts were present, indicating ongoing bone resorption. Osteoblasts were also observed, although in fewer numbers. In contrast, the propolis-treated group [Figure 3b] showed a noticeable increase in osteoblast and slightly reduced osteoclast presence. The early appearance of osteoblasts suggests the initiation of bone formation processes, reflecting a regenerative response to TAD placement, particularly in the presence of topical propolis.
The histological sections on Day 7 illustrate further progression of bone remodeling at the TAD site. In the control group [Figure 4a], osteoclasts remain prominent, indicating ongoing bone resorption. An increase in osteoblast presence is also evident compared to Day 3, with cuboidal cells aligning along bone-forming surfaces.
In the propolis-treated group [Figure 4b], a substantial increase in osteoblast number and activity was observed. Osteoblasts appeared more numerous and well-organized along the bone surface. In contrast, osteoclast numbers were noticeably reduced. These findings suggest that topical application of propolis gel accelerates osteoblast activation while simultaneously inhibiting osteoclast activity, thereby promoting bone formation at an earlier stage.
H and E-stained histological section shows bone tissue on Day 14 after TAD placement and propolis gel application [Figure 5]. In the control group, osteoclasts are still present but reduced in number and appear singly, indicating a decline in resorptive activity. Osteoblasts are more visible, marking the early phase of bone formation. In the treatment group, osteoclasts are markedly diminished, while osteoblasts are abundant, mature, and aligned along the bone surface. Their organized appearance and thicker layer suggest more advanced and stable osteogenesis compared to the control.
Quantitative analysis of osteoclast
The mean osteoclast count was consistently higher in the control group compared to the propolis-treated group at all-time points. On Day 3, osteoclasts were 12.80 ± 3.11 (control) versus 8.60 ± 1.34 (propolis), p = 0.024. On Day 7, counts were 6.60 ± 1.34 versus 4.40 ± 0.54, p = 0.009. By Day 14, the difference became more pronounced (4.40 ± 0.89 vs. 0.80 ± 1.10, p = 0.001) [Figures 3-5]. These results indicate that 10% propolis gel significantly reduced osteoclast numbers during bone remodeling following TAD placement [Table 1].
| Time point | Control (Mean±SD) | Propolis (Mean±SD) | p-value |
|---|---|---|---|
| Day-3 | 12.80±3.11 | 8.60±1.34 | 0.024* |
| Day-7 | 6.60±1.34 | 4.40±0.54 | 0.009* |
| Day-14 | 4.40±0.89 | 0.80±1.10 | 0.000* |
Quantitative analysis of osteoblast
Osteoblast counts were significantly higher in the propolis-treated group at all-time points. On Day 3, the count was 94.80 ± 20.81 versus 41.20 ± 21.29 in the control (p = 0.004). On Day 7, it increased to 219.00 ± 16.34 versus 171.80 ± 18.17 (p = 0.004), and peaked on Day 14 at 296.00 ± 24.17 versus 215.60 ± 22.11 (p = 0.001). These findings confirm the stimulatory effect of 10% propolis gel on osteoblast proliferation during bone remodeling [Table 2].
| Time point | Control (Mean±SD) | Propolis (Man±SD) | p-value |
|---|---|---|---|
| Day-3 | 41.20±21.29 | 94.80±20.81 | 0.004* |
| Day-7 | 171.80±18.17 | 219.00±16.34 | 0.004* |
| Day-14 | 215.60±22.11 | 296.00±24.17 | 0.001* |
Quantitative analysis of RANKL expression
Quantitative analysis of RANKL expression showed significant differences between the control and propolis groups on Days 3 and 7, but not on Day 14. On Day 3, the propolis group demonstrated significantly higher RANKL levels (0.062 ± 0.016) compared to the control group (0.028 ± 0.004; p = 0.002), reflecting activation of early inflammatory and remodeling signals following TAD insertion. On Day 7, RANKL expression remained elevated in the propolis group (0.066 ± 0.023) compared with the control group (0.038 ± 0.008; p = 0.034). By Day 14, however, RANKL levels converged between the groups, with no significant difference observed (propolis: 0.042 ± 0.011 vs. control: 0.036 ± 0.011; p = 0.421). This pattern suggests that propolis does not inhibit early RANKL signaling but influences downstream remodeling dynamics in a time-dependent manner [Table 3].
| Time point | Control (Mean±SD) | Propolis (Mean±SD) | p-value |
|---|---|---|---|
| Day-3 | 0.028±0.004 | 0.062±0.016 | 0.002* |
| Day-7 | 0.038±0.008 | 0.066±0.023 | 0.034* |
| Day-14 | 0.036±0.011 | 0.042±0.011 | 0.421 |
Effect of duration of propolis application on osteoclast and osteoblast count
Linear regression analysis revealed a strong positive correlation between the duration of propolis application and osteoblast numbers (R2 = 0.935) and a strong negative correlation with osteoclast numbers (R2 = 0.859). These findings indicate that prolonged application of propolis enhances osteogenesis and suppresses bone resorption [Table 4]. RANKL expression in the propolis group decreased over time, from 0.066 ± 0.011 (Day 3) to 0.058 ± 0.008 (Day 7) and 0.044 ± 0.005 (Day 14), with an R2 of 0.53, p = 0.001, indicating a moderate time-related decline [Table 4].
| Group | Time | R-square (R2) | ||
|---|---|---|---|---|
| Day-3, (Mean±SD) | Day-7, (Mean±SD) | Day-14, (Mean±SD) | ||
| Osteoclast | 8.60±1,34 | 4.40±0.54 | 0.80±1.10 | 0.859 |
| Osteoblast | 94.80±20.813 | 219.00±16.340 | 296.00±24.166 | 0.935 |
| RANKL | 0.066±0.011 | 0.058±0.008 | 0.044±0.005 | 0.53 |
Linear regression analysis. All three time-dependent trends were statistically significant (osteoclast R2 = 0.859, p < 0.001; osteoblast R2 = 0.935, p < 0.001; RANKL R2 = 0.530, p = 0.001). RANKL: Receptor activator of nuclear factor κB ligand.
Analysis relationship between RANKL expression and both osteoclast and osteoblast
Pearson correlation analysis revealed significant relationships between RANKL expression and both osteoblast and osteoclast counts. RANKL showed a moderate positive correlation with osteoblasts (r = 0.500, p = 0.005) and a moderate negative correlation with osteoclasts (r = −0.583, p = 0.001). These findings suggest that increased RANKL expression is associated with higher osteoblast activity and lower osteoclast numbers during the bone remodeling process.
DISCUSSION
Although (TADs) are designed as temporary anchorage units and are not intended to achieve osseointegration, the biological response of the surrounding bone during the early healing phase remains clinically relevant. Following TAD insertion, the surrounding bone undergoes a well-documented sequence of biological events, including initial inflammation, osteoclastic bone resorption, and subsequent osteoblastic repair. Excessive or prolonged bone resorption during this early phase may adversely affect the local peri-implant environment and contribute to early loosening, even in temporary devices.
In this context, the present study does not aim to suggest that 10% Trigona sp. propolis gel enhances the mechanical stability or longevity of TADs. Rather, the findings indicate that propolis exerts a biological modulatory effect on early peri-implant bone remodeling, characterized by reduced osteoclast activity, increased osteoblast numbers, and time-dependent changes in RANKL expression. These effects reflect modulation of cellular dynamics during the early healing phase, rather than direct mechanical reinforcement or osseointegration.
Bone remodeling is a complex biological process that depends on a balance between osteoclastic resorption and osteoblastic bone formation. In the context of TAD placement, excessive osteoclastic activity triggered by surgical trauma and inflammation can compromise implant stability.[6] Propolis appears to counteract this imbalance by modulating osteoclastogenesis through anti-inflammatory and molecular pathways.
Bone remodeling induced by orthodontic force involves complex cellular and molecular responses, including osteoclast activation, osteoblast differentiation, and regulation of the RANK–RANKL–OPG signaling pathway. Mechanical loading and surgical trauma associated with temporary anchorage device placement initiate inflammatory and resorptive phases that are essential for subsequent bone repair. These biological responses have been well describedin orthodontic tooth movement and anchorage-related bone remodeling processes.[13,14]
The bioactive compounds in propolis are known to interact with key inflammatory and bone-regulatory pathways, including the RANK-RANKL-OPG system. Rather than directly suppressing RANKL expression, propolis may modulate the temporal dynamics of RANKL signaling during bone remodeling.[7,8]
In this study, ELISA analysis showed significantly higher RANKL levels in the propolis group on Days 3 and 7, reflecting an early and active bone turnover phase following TAD placement. This finding is biologically plausible, as RANKL expression is typically upregulated during the early inflammatory and resorptive phase of bone remodeling.[7]However, by Day 14, RANKL expression no longer differed significantly between groups, despite a continued reduction in osteoclast numbers in the propolis-treated group. This suggests osteoclast suppression at later stages may not be solely dependent on RANKL concentration, but rather on downstream or compensatory mechanisms. Several explanation may account for this observation: (1) a physiological decline in RANKL expression during the late remodeling phase, (2) increased activity of OPG, which neutralizes RANKL signaling without altering its measurable concentration, (3) time-dependent biological effects of propolis that are more pronounced during early remodeling stages, and (4) limitations in detecting localized RANKL activity in advanced healing phases.
These findings are consistent with previous studies reporting that propolis, particularly when used as a local adjunct, modulates bone resorption primarily during the early phases of healing while maintaining long-term biological effects through alternative signaling pathways.[8] Collectively, these results indicate that while RANKL expression alone may not fully explain osteoclast suppression at later stages, propolis continues to exert regulatory effects on bone resorption, potentially through downstream mediators such as Nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) inhibition or enhanced OPG activity.
In addition to its inhibitory effect on osteoclasts, 10% propolis gel significantly increased osteoblast numbers throughout the study period. Statistical analysis using independent t-tests showed that osteoblast counts were significantly higher in the treatment group compared to the control group on Days 3, 7, and 14 (p < 0.05). The stimulatory effects of propolis on osteoblasts can be attributed to its bioactive components, flavonoids, phenolic acids, and esters, which promote osteoblast proliferation and differentiation. Previous studies have shown that these compounds activate the Wnt/β-catenin signaling pathway, a key regulator of osteogenesis.[9] Furthermore, propolis reduces inflammatory cytokines such as Tumor Necrosis Factor-alpha and Interleukin-1 beta, which otherwise inhibit osteoblast activity.[15]
Given that propolis after TAD placement can provoke local inflammation, propolis provides a dual benefit: It supports the formation of new bone while mitigating inflammation-induced delays in bone healing. This osteogenic potential makes it a valuable adjunct in improving peri-implant bone quality and supporting a favorable biological environment around TADs.[11]
Linear regression analysis revealed strong correlations between the duration of propolis application and both osteoblast and osteoclast counts, highlighting the time-dependent biological effects of propolis. Prolonged exposure resulted in increased osteoblast numbers and a sustained reduction in osteoclast activity. These effects may be due to sustained modulation of bone-regulating signaling pathways and prolonged exposure to key bioactive agents such as caffeic acid phenethyl ester.[16]
The most pronounced changes were observed on Day 14, corresponding to the active remodeling phase characterized by new bone matrix formation and reduced resorptive activity. Although RANKL levels did not differ significantly at this time point, the continued reduction in osteoclast numbers suggests functional suppression of bone resorption mediated by downstream regulatory mechanisms rather than direct RANKL inhibition.[17]
The findings of this study have potential biological implications for orthodontic treatment involving TADs. While TADs are designed as temporary anchorage units, their early clinical performance is influenced by the biological response of the surrounding bone during the early healing phase.[18]
Excessive bone resorption around TADs may contribute to peri-implant bone loss and compromise the local anchorage environment. Based on the present findings, the application of 10% propolis gel may support per-implant bone remodeling by: (1) reducing osteoclast activity and limiting early bone resorption, (2) enhancing osteoblast-mediated bone formation, and (3) providing additional antimicrobial and anti-inflammatory effects.
Importantly, these effects reflect biological modulation of peri-implant bone healing, rather than direct enhancement of mechanical TAD stability. Furthermore, the gel formulation is easy to apply topically, making it a practical, non-invasive adjunct for clinical use. These findings suggest that biological modulation using propolis could be integrated into TAD placement protocols to enhance outcomes and minimize complications.
While the results of this study are promising, several limitations must be considered: (1). The main limitation of this study is the absence of a placebo (CMC-only) group, which restricted our ability to separate the biological effects of propolis from vehicle-related influences. This was due to institutional ethical limits on animal numbers. Future work should incorporate a placebo group to improve internal validity. (2) The study observed outcomes only up to Day 14 post-application. Long-term effects of propolis on chronic bone remodeling were not evaluated. (3) Limited Molecular Data The study measured only the cell counts of osteoclasts and osteoblasts and RANKL expression. Additional data, such as OPG levels, NFATc1, or Wnt/β-catenin pathway markers, would provide deeper insights into the molecular mechanisms. Future research should explore these molecular pathways and evaluate the long-term clinical efficacy of propolis in orthodontic and implant applications.
CONCLUSION
Topical application of 10% Trigona sp. propolis gel significantly enhanced bone remodeling following TAD placement by reducing osteoclast numbers, increasing osteoblast proliferation, and modulating RANKL expression over time. The most pronounced cellular changes were observed on Day 14, characterized by increased osteoblast activity and a sustained reduction in osteoclast numbers, consistent with an active bone remodeling phase. Linear regression analysis confirmed that these effects were cumulative and time-dependent.
These findings strongly indicate that propolis has promising potential as a local adjunctive agent in orthodontics to promote peri-implant bone healing and support a favorable biological environment around TADs during the early healing phase. Future studies incorporating longer observation periods, placebo-controlled designs, and additional molecular markers are required to elucidate the mechanisms and clinical relevance of propolis in orthodontic applications.
Acknowledgments:
We would like to thank the Orthodontic Department at Hasanuddin University for their laboratory support.
Author’s Contributions:
FA: Conceptualization, Investigation, Resources, Project administration; Supervision, Validation, Visualization, Writing - original draft and review and editing, Funding acquisition, Methodology; BMR: Funding acquisition, Supervision, Conceptualization, Investigation, Formal analysis, Writing - original draft and review and editing, Formal analysis; EHH: Investigation, Visualization, Writing - original draft, Software, Methodology, Resources, Data curation; EE: Validation, Methodology, Writing - original draft and review and editing, Supervision, Formal analysis; ASP: Methodology, Writing -original draft and review and editing, Data curation; DRN: Investigation,Resources, Supervision, Writing - original draft and review and editing; ZIP: Data curation, Formal analysis, Writing -original draftand review and editing.
Ethical approval:
The research/study was approved by the Institutional Review Board at The Health Research Ethics Commission Faculty of Dentistry, Hasanuddin University, Makassar, number 091/KEPK FKG-RSGMP UH/EA/III/2025, dated 24th March, 2025.
Declaration of patient consent:
Patient’s consent not required as there are no patients in this study.
Conflicts of interest:
There are no conflicts of interest.
Use of artificial intelligence (AI)-assisted technology for manuscript preparation:
The authors confirm that they have used artificial intelligence (AI)-assisted technology for language polishing and grammar correction, with no involvement in data generation, data analysis, or interpretation.
Financial support and sponsorship: Nil.
References
- Orthodontic miniscrew implants: Clinical applications. Am J Orthod Dentofacial Orthop. 2014;145:425-32.
- [Google Scholar]
- The effect of cortical bone thickness on the stability of orthodontic mini-implants. Angle Orthod. 2009;79:634-40.
- [Google Scholar]
- Enhancing orthodontic precision: A comprehensive review of temporary anchorage devices. J Dent Panacea. 2024;6:92-102.
- [CrossRef] [Google Scholar]
- Temporary anchorage devices in orthodontics: A review. IP Indian J Orthod. 2020;6:222-8.
- [CrossRef] [Google Scholar]
- Indication and uses of temporary anchorage device in orthodontic. Int J Community Med Public Health. 2021;9:454-9.
- [CrossRef] [Google Scholar]
- The RANK-RANKL-OPG system: A multifaceted regulator of homeostasis, immunity, and cancer. Medicina (Kaunas). 2023;59:1752.
- [CrossRef] [PubMed] [Google Scholar]
- Honey, propolis, and royal jelly: A comprehensive review of their biological actions and health benefits. Oxid Med Cell Longev. 2017;2017:1259510.
- [CrossRef] [PubMed] [Google Scholar]
- Systemic propolis stimulates new bone formation at the expanded suture: A histomorphometric study. Angle Orthod. 2013;83:286-91.
- [CrossRef] [PubMed] [Google Scholar]
- Impact of propolis administration on osteocrin expression and osteoblast-toosteoclast ratio in the femurs of rats fed a high-fat diet. Glob Med Health Commun. 2024;12:126-30.
- [CrossRef] [Google Scholar]
- Osteoclast differentiation and activation. Nature. 2003;423:337-42.
- [CrossRef] [PubMed] [Google Scholar]
- Cellular, molecular, and tissue-level reactions to orthodontic force. Am J Orthod Dentofacial Orthop. 2006;129:469.e1-469.e32.
- [CrossRef] [PubMed] [Google Scholar]
- Socket preservation using a combination of propolis extract and bovine bone graft towards the expression of receptor activator of nuclear?B ligand and osteoprogerin. Folia Med (Plovdiv). 2023;65:737-43.
- [CrossRef] [PubMed] [Google Scholar]
- Application of propolis in protecting skeletal and periodontal health-a systematic review. Molecules. 2021;26:3156.
- [CrossRef] [PubMed] [Google Scholar]
- Bioactive compounds from propolis on bone homeostasis: A narrative review. Antioxidants (Basel). 2025;14:81.
- [CrossRef] [PubMed] [Google Scholar]
- Applications of honeybee-derived products in bone tissue engineering. Bone Rep. 2024;20:101740.
- [CrossRef] [PubMed] [Google Scholar]
- The effect of propolis on increasing the number of osteoblasts and chondrocytes, and decreasing the number of osteoclasts in wistar rats (Rattusnovergicus) with femoral bone fracture. IOSR J Dent Med Sci. 2016;15:90-5.
- [Google Scholar]