1.Role of caffeine and ethanol in modulating expression of Receptor Activator of Nuclear Factor κβ (RANK) and Osteoprotegerin (OPG) during orthodontic tooth movement: An in vivo study.
Ardiansyah S. PAWINRU ; Eka ERWANSYAH ; Eddy Heriyanto HABAR ; Abul FAUZI ; AMINULLAH ; Gita GAYATRI ; Yustisia PUSPITASARI ; Ita Purnama ALWI ; Andi Husnul HASANAH
Acta Medica Philippina 2026;60(8):115-122
BACKGROUND AND OBJECTIVES
Orthodontic tooth movement is driven by bone remodeling influenced by systemic factors, including caffeine and ethanol. This study aimed to investigate the effects of caffeine and ethanol on the expression of Receptor Activator of Nuclear Factor κβ (RANK) and Osteoprotegerin (OPG), key bone remodeling biomarkers, during orthodontic tooth movement.
METHODSA laboratory experimental study was conducted on 30 male Wistar rats divided into three groups: K1 (orthodontic force only), K2 (force + caffeine), and K3 (force + ethanol). Orthodontic force was applied using Ni-Ti coil springs. Caffeine and ethanol were administered orally daily. On days 7 and 14, maxillary tissues were collected and analyzed via immunohistochemistry for RANK and OPG expression. Data were analyzed using One-Way ANOVA and Independent Sample T-tests with significance at pRESULTS
Caffeine and ethanol administration increased RANK and OPG expression compared to controls; however, only the ethanol group showed a significant increase in RANK expression on day 14 (p = 0.044). OPG expression was significantly higher in treatment groups at both time points (pCONCLUSION
Caffeine and ethanol modulate bone remodeling marker expression during orthodontic force application, with ethanol significantly increasing RANK expression at later stages. Further studies are needed to clarify the clinical implications for orthodontic treatment.
Animals ; Tooth Movement Techniques ; Tooth Movement ; Osteoprotegerin ; Role ; Movement ; Ethanol ; Bone Remodeling ; Caffeine ; Immunohistochemistry
2.The role of crosslinked collagen-hydroxyapatite on the properties of tissue graft material.
Fitria Rahmitasari ; Widyasri Prananingrum ; Sularsih ; Moh Basroni Rizal ; Puguh Bayu Prabowo
Acta Medica Philippina 2026;60(6):99-106
OBJECTIVE
This review article aims to determine the properties, uses, toxicity, and other side effects of crosslinking agents in tissue scaffolds when applied in vitro and in vivo.
METHODSA literature search was performed using the PubMed-NCBI (MEDLINE) database (https://pubmed.ncbi.nlm. nih.gov/) with keywords: crosslinking reagent, collagen, hydroxyapatite, and bone regeneration. GRADE criteria were used to assess the quality of evidence.
RESULTSA total of six articles were included in the study. Improved mechanical properties of collagen-hydroxyapatite scaffolds with high porosity can be achieved by employing crosslinking methods, including physical dehydrothermal (DHT) treatment, chemical treatment with glutaraldehyde (GA), Microbial Transglutaminase (mTGase), 1‐ethyl‐3‐(3‐ dimethylaminopropyl) carbodiimide (EDAC), or a combination of both DHT and EDAC. Furthermore, the crosslinking of EDAC and DHT can lead to forming ester bonds between activated carboxyl groups and hydroxyl groups.
CONCLUSIONThe combination of DHT and EDAC crosslinking can increase mechanical strength, make the pore size appropriate, make the scaffold more stable, and support cell adhesion so that new cells can grow, and the process of osteogenesis can run more optimally.
Cross-linking Reagents ; Collagen ; Durapatite ; Hydroxyapatite ; Bone Regeneration
3.Role of caffeine and ethanol in modulating expression of Receptor Activator of Nuclear Factor κβ (RANK) and Osteoprotegerin (OPG) during orthodontic tooth movement: An in vivo study.
Ardiansyah S. PAWINRU ; Eka ERWANSYAH ; Eddy Heriyanto HABAR ; Abul FAUZI ; AMINULLAH ; Gita GAYATRI ; Yustisia PUSPITASARI ; Ita Purnama ALWI ; Andi Husnul HASANAH
Acta Medica Philippina 2026;60(8):115-122
BACKGROUND AND OBJECTIVES
Orthodontic tooth movement is driven by bone remodeling influenced by systemic factors, including caffeine and ethanol. This study aimed to investigate the effects of caffeine and ethanol on the expression of Receptor Activator of Nuclear Factor κβ (RANK) and Osteoprotegerin (OPG), key bone remodeling biomarkers, during orthodontic tooth movement.
METHODSA laboratory experimental study was conducted on 30 male Wistar rats divided into three groups: K1 (orthodontic force only), K2 (force + caffeine), and K3 (force + ethanol). Orthodontic force was applied using Ni-Ti coil springs. Caffeine and ethanol were administered orally daily. On days 7 and 14, maxillary tissues were collected and analyzed via immunohistochemistry for RANK and OPG expression. Data were analyzed using One-Way ANOVA and Independent Sample T-tests with significance at pRESULTS
Caffeine and ethanol administration increased RANK and OPG expression compared to controls; however, only the ethanol group showed a significant increase in RANK expression on day 14 (p = 0.044). OPG expression was significantly higher in treatment groups at both time points (pCONCLUSION
Caffeine and ethanol modulate bone remodeling marker expression during orthodontic force application, with ethanol significantly increasing RANK expression at later stages. Further studies are needed to clarify the clinical implications for orthodontic treatment.
Animals ; Tooth Movement Techniques ; Tooth Movement ; Osteoprotegerin ; Role ; Movement ; Ethanol ; Bone Remodeling ; Caffeine ; Immunohistochemistry
4.Research progress on enhancing osseointegration properties of polyetheretherketone implants through various modification methods.
Shilai LIU ; Xiaoke FENG ; Chunxia CHEN
Journal of Biomedical Engineering 2025;42(2):417-422
This review article summarizes the current modification methods employed to enhance the osseointegration properties of polyetheretherketone (PEEK), a novel biomaterial. Our analysis highlights that strategies such as surface treatment, surface modification, and the incorporation of bioactive composites can markedly improve the bioactivity of PEEK surfaces, thus facilitating their effective integration with bone tissue. However, to ensure widespread application of PEEK in the medical field, particularly in oral implantology, additional experiments and long-term clinical evaluations are required. Looking ahead, future research should concentrate on developing innovative modification techniques and assessment methodologies to further optimize the performance of PEEK implant materials. The ultimate goal is to provide the clinical setting with even more reliable solutions.
Benzophenones
;
Ketones/chemistry*
;
Polyethylene Glycols/chemistry*
;
Osseointegration
;
Humans
;
Polymers
;
Biocompatible Materials/chemistry*
;
Surface Properties
;
Prostheses and Implants
;
Dental Implants
5.Buqi-Tongluo Decoction inhibits osteoclastogenesis and alleviates bone loss in ovariectomized rats by attenuating NFATc1, MAPK, NF-κB signaling.
Yongxian LI ; Jinbo YUAN ; Wei DENG ; Haishan LI ; Yuewei LIN ; Jiamin YANG ; Kai CHEN ; Heng QIU ; Ziyi WANG ; Vincent KUEK ; Dongping WANG ; Zhen ZHANG ; Bin MAI ; Yang SHAO ; Pan KANG ; Qiuli QIN ; Jinglan LI ; Huizhi GUO ; Yanhuai MA ; Danqing GUO ; Guoye MO ; Yijing FANG ; Renxiang TAN ; Chenguang ZHAN ; Teng LIU ; Guoning GU ; Kai YUAN ; Yongchao TANG ; De LIANG ; Liangliang XU ; Jiake XU ; Shuncong ZHANG
Chinese Journal of Natural Medicines (English Ed.) 2025;23(1):90-101
Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
Animals
;
NFATC Transcription Factors/genetics*
;
Drugs, Chinese Herbal/pharmacology*
;
Ovariectomy
;
Osteoclasts/metabolism*
;
Female
;
Osteogenesis/drug effects*
;
Rats, Sprague-Dawley
;
Rats
;
NF-kappa B/genetics*
;
Osteoporosis/genetics*
;
Signal Transduction/drug effects*
;
Bone Resorption/genetics*
;
Cell Differentiation/drug effects*
;
Humans
;
RANK Ligand/metabolism*
;
Mitogen-Activated Protein Kinases/genetics*
;
Transcription Factors
6.Salidroside inhibits osteoclast differentiation based on osteoblast-osteoclast interaction via HIF-1a pathway.
Yutong JIN ; Yao WANG ; Chuan WANG ; Lingling ZHANG ; Dandan GAO ; Haizhao LIU ; Qingwen CAO ; Chenchen TIAN ; Yuhong BIAN ; Yue WANG
Chinese Journal of Natural Medicines (English Ed.) 2025;23(5):572-584
This study investigated the regulatory potential of salidroside (SAL), a primary active compound in Rhodiola rosea L., on osteoclast differentiation by modulating the hypoxia-inducible factor 1-alpha (HIF-1a) pathway in osteoblasts. Luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay were employed to validate whether the receptor activator of nuclear factor-?B ligand (RANKL) is the downstream target gene of HIF-1a in osteoblasts. The study also utilized lipopolysaccharide (LPS)-induced mouse osteolysis to examine the impact of SAL on osteolysis in vivo. Furthermore, conditioned medium (CM) from SAL-pretreated osteoblasts was used to investigate the paracrine effects on osteoclastogenesis through the HIF-1a pathway. Hypoxic condition-induced overexpression of HIF-1a upregulated RANKL levels by binding to the RANKL promoter and enhancing transcription in osteoblastic cells. In vivo, SAL significantly alleviated bone tissue hypoxia and decreased the expression of HIF-1a by downregulating the expression of RANKL, vascular endothelial growth factor (VEGF), interleukin 6 (IL-6), and angiopoietin-like 4 (ANGPTL4). In the paracrine experiment, conditioned media from SAL-pretreated osteoblasts inhibited differentiation through the HIF-1a/RANKL, VEGF, IL-6, and ANGPTL4 pathways. RANKL emerges as the downstream target gene regulated by HIF-1a in osteoblasts. SAL significantly alleviates bone tissue hypoxia and bone loss in LPS-induced osteolysis through the HIF-1a/RANKL, VEGF, IL-6, and ANGPTL4 pathways. SAL inhibits osteoclast differentiation by regulating osteoblast paracrine secretion.
Animals
;
Osteoblasts/cytology*
;
Hypoxia-Inducible Factor 1, alpha Subunit/genetics*
;
Glucosides/administration & dosage*
;
Cell Differentiation/drug effects*
;
Phenols/administration & dosage*
;
Mice
;
Osteoclasts/metabolism*
;
RANK Ligand/genetics*
;
Rhodiola/chemistry*
;
Osteogenesis/drug effects*
;
Signal Transduction/drug effects*
;
Interleukin-6/genetics*
;
Male
;
RAW 264.7 Cells
;
Osteolysis/genetics*
;
Humans
;
Mice, Inbred C57BL
7.Threshold-Effect Associations of Serum 25-hydroxyvitamin D on Bone Turnover Markers and GC rs2282679 Variants in Chinese Women of Childbearing Age.
Xiao Yun SHAN ; Yu Ting LI ; Xia Yu ZHAO ; Yi Chun HU ; Si Ran LI ; Hui di ZHANG ; Yang CAO ; Rui WANG ; Li Chen YANG
Biomedical and Environmental Sciences 2025;38(4):433-446
OBJECTIVE:
This study aimed to investigate possible serum 25-hydroxyvitamin D [25(OH)D] cutoffs for the associations between 25(OH)D and Bone turnover markers (BTMs), and how GC gene variation influences such cutoffs in Chinese women of childbearing age.
METHODS:
In total, 1,505 non-pregnant or non-lactating women (18-45 years) were recruited from the 2015 Chinese Adult Chronic Disease and Nutrition Surveillance. Serum 25(OH)D, osteocalcin (OC), procollagen type 1 N-terminal propeptide (P1NP), β-CrossLaps of type 1 collagen containing cross-linked C-telopeptide (β-CTX), and single nucleotide polymorphisms were determined. Locally weighted regression and smoothing scatterplot and segmented regression were performed to estimate the 25(OH)D thresholds.
RESULTS:
The median serum 25(OH)D was 16.63 (11.96-22.55) ng/mL and the prevalence of low serum 25(OH)D (< 12 ng/mL) was 25.2%. Women with the lowest 25(OH)D had the highest β-CTX. After adjustment for the confounders, 25(OH)D cutoffs for OC [14.04 (12.84-15.23) ng/mL], β-CTX [13.94 (12.49-15.39) ng/mL], and P1NP [13.87 (12.37-15.37) ng/mL] in the whole population, cutoffs for OC [12.30 (10.68-13.91) ng/mL], β-CTX [12.23 (10.22-14.23) ng/mL], and P1NP [11.85 (10.40-13.31) ng/mL] in women with the GC rs2282679 G allele, and cutoffs for OC [12.75 (11.81-13.68) ng/mL], β-CTX [13.05 (11.78-14.32) ng/mL], and P1NP [12.81 (11.57-14.06) ng/mL] in women with the GC rs2282679 T allele, were observed. Below these cutoffs, BTMs were negatively associated with 25(OH)D, while above these cutoffs, BTMs plateaued.
CONCLUSION
In Chinese women of childbearing age, there were thresholds effect of serum 25(OH)D concentrations on BTMs. The results indicated that serum 25(OH)D concentrations < 13.87 ng/mL in this population had adverse influences on maintaining bone remodeling. BTMs were suppressed at a relatively lower serum 25(OH)D in women with the GC rs2282679 G allele compared with those with the T allele.
Humans
;
Female
;
Vitamin D/blood*
;
Adult
;
Middle Aged
;
Polymorphism, Single Nucleotide
;
Adolescent
;
Young Adult
;
China
;
Biomarkers/blood*
;
Bone Remodeling/genetics*
;
Vitamin D-Binding Protein/genetics*
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Procollagen/blood*
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Osteocalcin/blood*
;
Peptide Fragments/blood*
;
East Asian People
8.L-shape technique with concentrated growth factor for horizontal bone defects in the maxillary anterior region: a clinical and radiographic study.
Ruiwen SHI ; Hu YANG ; Yue LIU ; Yilin SHI ; Shengben ZHANG ; Yu LIU ; Feng SONG ; Jing LAN
West China Journal of Stomatology 2025;43(1):76-83
OBJECTIVES:
To study the clinical effect of the L-shape technique combined with concentrated growth factor on the horizontal bone defects of maxillary anterior teeth.
METHODS:
Twenty-five implants from 25 patients who underwent single maxillary anterior tooth implantation with simultaneous bone grafting were selected as the study subjects. Based on the bone grafting techniques, the patients were divided into a test group (L-shaped technique with guided bone regeneration combined with concentrated growth factor, 11 cases) and a control group (traditional guided bone regeneration combined with concentrated growth factor, 14 cases). The early discomfort and wound healing conditions in the two groups at two weeks after surgery were compared. The horizontal bone thickness, vertical bone thickness, and grayscale values in the augmentation area were measured immediately postsurgery and six months after surgery. Implant stability, hard tissue resorption within six months, and grayscale values were compared between the two groups.
RESULTS:
Differences in early discomfort, wound healing, implant stability, and grayscale values between the two groups were not statistically significant (P>0.05). Vertical bone thickness in the test group was significantly better than that in the control group at six months after surgery (P<0.05). The variation in horizontal bone thickness in the test group was significantly higher than that in the control group (P<0.05).
CONCLUSIONS
The application of the L-shape technique with concentrated growth factor for horizontal bone defects in the anterior maxillary area yielded satisfactory short-term results in terms of bone augmentation, early discomfort, wound healing, and implant stability at six months after surgery.
Humans
;
Maxilla/diagnostic imaging*
;
Intercellular Signaling Peptides and Proteins/therapeutic use*
;
Wound Healing
;
Bone Transplantation/methods*
;
Dental Implantation, Endosseous/methods*
;
Bone Regeneration
;
Male
;
Female
;
Adult
;
Dental Implants, Single-Tooth
;
Middle Aged
9.Guided bone regeneration therapy based on plaque control of peri-implantitis with follow-up at 7 years.
Wenqi SU ; Dandan ZHANG ; Yan CHENG ; Wenjie CUI ; Lang LEI ; Houxuan LI
West China Journal of Stomatology 2025;43(1):133-139
Peri-implantitis is a pathologic condition associated with dental plaque that occurs in the implant tissue and is characterized by inflammation of the mucous membrane surrounding the implant, followed by the progressive loss of supporting bone. In this study, a case of guided bone regeneration therapy based on plaque control of peri-implant inflammation was reported. Four years after surgery for the left second premolar implant, the patient presented with "left lower posterior tooth swelling and discomfort for more than 2 years". The X-ray periapical film showed a decrease in distal bone mineral density of implant, and the clinical diagnosis was peri-implantitis of the left second premolar. Implants underwent guided bone regeneration and regular periodontal maintenance treatment. Re-examination at 3.5 months, 11 months, 18 months, and 7 years showed that the alveolar bone height and bone mineral density were stable, and the periodontal depth became shallow. However, the gingival recession was mild. In the present case, follow-up at 7 years demonstrated that the clinical periodontal indexes could be remarkably improved after complete periodontal treatment for peri-implantitis, and the alveolar bone could be well restored and regenerated.
Humans
;
Peri-Implantitis/etiology*
;
Follow-Up Studies
;
Bone Regeneration
;
Guided Tissue Regeneration, Periodontal/methods*
;
Dental Plaque/prevention & control*
;
Male
;
Female
;
Dental Implants/adverse effects*
10.Relationship between fluid shear stress in alveolar bone under orthodontic forces and bone remodeling rate.
Bin WU ; Kexin HU ; Fan YANG ; Yi LU ; Di JIANG ; Yang YI ; Bin YAN
West China Journal of Stomatology 2025;43(2):190-196
OBJECTIVES:
This study explores the differences in fluid flow within alveolar cancellous bone at various sites under orthodontic forces and elucidates the relationship between fluid shear stress and bone remodeling. These fin-dings lay the groundwork for understanding the biomechanical mechanisms of orthodontic tooth movement.
METHODS:
Stress relaxation tests were performed on human alveolar bone samples to determine material parameters by using the Prony series. An inverse model of alveolar bone was then developed for numerical simulations of fluid-structure interactions to calculate fluid flow within cancellous bone. Meanwhile, a rat model of tooth movement was established to investigate variations in bone remodeling speeds across different regions.
RESULTS:
The microstructural distribution of cancellous alveolar bone was similar in humans and rats. The bone volume fraction and trabecular thickness gradually decreased from root cervical region to root apical region, while the trabecular space gradually increased. Under the influence of orthodontic forces, fluid shear stress within cancellous bone showed spatial variability across different levels, with the highest shear stress occurring at the root apical region, ranging from 0 to 0.936 6 Pa. Additionally, the rat model of tooth movement indicated that bone remodeling occurred more rapidly at the root apical region.
CONCLUSIONS
Fluid stimulation has a remarkable effect on al-veolar bone remodeling, causing changes in the structure of alveolar bone and ultimately regulating the speed of structu-ral remodeling.
Bone Remodeling
;
Animals
;
Tooth Movement Techniques
;
Rats
;
Alveolar Process/physiology*
;
Stress, Mechanical
;
Humans
;
Biomechanical Phenomena
;
Cancellous Bone/physiology*
;
Shear Strength


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