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Biomedicines Jan 2024Numerous pieces of evidence have supported the therapeutic potential of photobiomodulation (PBM) to modulate bone remodeling on mechanically stimulated teeth, proving...
Optimization of a Photobiomodulation Protocol to Improve the Cell Viability, Proliferation and Protein Expression in Osteoblasts and Periodontal Ligament Fibroblasts for Accelerated Orthodontic Treatment.
Numerous pieces of evidence have supported the therapeutic potential of photobiomodulation (PBM) to modulate bone remodeling on mechanically stimulated teeth, proving PBM's ability to be used as a coadjuvant treatment to accelerate orthodontic tooth movement (OTM). However, there are still uncertainty and discourse around the optimal PBM protocols, which hampers its optimal and consolidated clinical applicability. Given the differential expression and metabolic patterns exhibited in the tension and compression sides of orthodontically stressed teeth, it is plausible that different types of irradiation may be applied to each side of the teeth. In this sense, this study aimed to design and implement an optimization protocol to find the most appropriate PBM parameters to stimulate specific bone turnover processes. To this end, three levels of wavelength (655, 810 and 940 nm), two power densities (5 and 10 mW/cm) and two regimens of single and multiple sessions within three consecutive days were tested. The biological response of osteoblasts and periodontal ligament (PDL) fibroblasts was addressed by monitoring the PBM's impact on the cellular metabolic activity, as well as on key bone remodeling mediators, including alkaline phosphatase (ALP), osteoprotegerin (OPG) and receptor activator of nuclear factor κ-B ligand (RANK-L), each day. The results suggest that daily irradiation of 655 nm delivered at 10 mW/cm, as well as 810 and 940 nm light at 5 mW/cm, lead to an increase in ALP and OPG, potentiating bone formation. In addition, irradiation of 810 nm at 5 mW/cm delivered for two consecutive days and suspended by the third day promotes a downregulation of OPG expression and a slight non-significant increase in RANK-L expression, being suitable to stimulate bone resorption. Future studies in animal models may clarify the impact of PBM on bone formation and resorption mediators for longer periods and address the possibility of testing different stimulation periodicities. The present in vitro study offers valuable insights into the effectiveness of specific PBM protocols to promote osteogenic and osteoclastogenesis responses and therefore its potential to stimulate bone formation on the tension side and bone resorption on the compression side of orthodontically stressed teeth.
PubMed: 38255285
DOI: 10.3390/biomedicines12010180 -
Osteoarthritis and Cartilage May 2024Osteoarthritis (OA) is a disease of joints, in which the bone under the articular cartilage undergoes increased remodelling activity. The question is whether a better... (Review)
Review
OBJECTIVE
Osteoarthritis (OA) is a disease of joints, in which the bone under the articular cartilage undergoes increased remodelling activity. The question is whether a better understanding of the causes and mechanisms of bone remodelling can predict disease-modifying treatments.
DESIGN
This review summarises the current understanding of the aetiology of OA, with an emphasis on events in the subchondral bone (SCB), and the cells and cytokines involved, to seek an answer to this question.
RESULTS
SCB remodelling across OA changes the microstructure of the SCB, which alters the load-bearing properties of the joint and seems to have an important role in the initiation and progression of OA. Bone remodelling is tightly controlled by numerous cytokines, of which Receptor Activator of NFκB ligand (RANKL) and osteoprotegerin are central factors in almost all known bone conditions. In terms of finding therapeutic options for OA, an important question is whether controlling the rate of SCB remodelling would be beneficial. The role of RANKL in the pathogenesis and progression of OA and the effect of its neutralisation remain to be clarified.
CONCLUSIONS
This review further makes the case for SCB remodelling as important in OA and for additional study of RANKL in OA, both its pathophysiological role and its potential as an OA disease target.
Topics: Humans; Cartilage, Articular; Cytokines; Ligands; Osteoarthritis; Osteoprotegerin; RANK Ligand
PubMed: 38160744
DOI: 10.1016/j.joca.2023.10.010 -
Drug Delivery and Translational Research Jul 2024Osteoarthritis is a bone and joint condition characterized pathologically by articular cartilage degenerative damage and can develop into a devastating and permanently...
Magnetic targeting of lornoxicam/SPION bilosomes loaded in a thermosensitive in situ hydrogel system for the management of osteoarthritis: Optimization, in vitro, ex vivo, and in vivo studies in rat model via modulation of RANKL/OPG.
Osteoarthritis is a bone and joint condition characterized pathologically by articular cartilage degenerative damage and can develop into a devastating and permanently disabling disorder. This investigation aimed to formulate the anti-inflammatory drug lornoxicam (LOR) into bile salt-enriched vesicles loaded in an in situ forming hydrogel as a potential local treatment of osteoarthritis. This was achieved by formulating LOR-loaded bilosomes that are also loaded with superparamagnetic iron oxide nanoparticles (SPIONs) for intra-muscular (IM) administration to improve joint targeting and localization by applying an external magnet to the joint. A 3.2 full factorial design was employed to develop the bilosomal dispersions and the optimized formula including SPION (LSB) was loaded into a thermosensitive hydrogel. Moreover, in vivo evaluation revealed that the IM administration of LSB combined with the application of an external magnet to the joint reversed carrageen-induced suppression in motor activity and osteoprotegerin by significantly reducing the elevations in mitogen-activated protein kinases, extracellular signal-regulated kinase, and receptor activator of nuclear factor kappa beta/osteoprotegerin expressions. In addition, the histopathological evaluation of knee joint tissues showed a remarkable improvement in the injured joint tissues. The results proved that the developed LSB could be a promising IM drug delivery system for osteoarthritis management.
Topics: Animals; Osteoarthritis; Hydrogels; Piroxicam; Male; RANK Ligand; Rats; Magnetic Iron Oxide Nanoparticles; Anti-Inflammatory Agents, Non-Steroidal; Disease Models, Animal; Liposomes; Rats, Wistar; Drug Delivery Systems
PubMed: 38158473
DOI: 10.1007/s13346-023-01503-8 -
The Saudi Dental Journal Dec 2023Vitamin D has been associated with an increased risk of tooth loss and the severity of periodontal diseases. This study aimed to evaluate the effect of vitamin D on...
OBJECTIVES AND BACKGROUND
Vitamin D has been associated with an increased risk of tooth loss and the severity of periodontal diseases. This study aimed to evaluate the effect of vitamin D on the clinical, radiographic, and serum level changes of bone turnover biomarkers in ligature-induced periodontitis.
METHODS
A total of 28 rats were included in this study and divided into test groups: Vitamin D supplement (VS), Vitamin D deficient (VD), and control (CG). Ligature-induced periodontal tissue destruction was performed and kept for 21 days. Clinical attachment and radiographic changes were recorded, and serum samples were tested for Osteoprotegerin (OPG), Dickkopf-1 (DKK1), Sclerostin (SOST), and Fibroblast growth factor 23 (FGF23) on the initial and final day of the study.
RESULTS
Groups that were made VD exhibited a more significant amount of clinical attachment loss (1.05 ± 0.50 mm) compared to the CG (0.83 ± 0.14 mm) and VS group (0.60 ± 0.13 mm), showing significant differences (p < 0.05). The radiographic alveolar bone loss amount was greater in the VD group compared to the other groups. For serum level assessment, the VD groups also exhibited a statistically significant reduction in the levels of OPG. They showed higher concentrations of DKK1, SOST, and FGF23 than other groups, with significant differences (p < 0.05).
CONCLUSION
The results revealed that Vitamin D may play a role in the progression of periodontal disease. It was found to affect both clinical parameters and bone turnover biomarkers, suggesting its potential impact on the disease process.
PubMed: 38107036
DOI: 10.1016/j.sdentj.2023.07.020 -
Journal of Orthopaedic Surgery and... Nov 2023The OPG/RANKL signal pathway was important regulation mechanism of bone remodeling cycle, but the effect of osteoprotegerin (OPG) and RANKL in osteoporosis was... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
The OPG/RANKL signal pathway was important regulation mechanism of bone remodeling cycle, but the effect of osteoprotegerin (OPG) and RANKL in osteoporosis was uncertain. We did a systematic review with meta-analysis to assess the association between serum OPG/RANKL and osteoporosis.
METHODS
The systematic search, data extraction, critical appraisal, and meta-analysis were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Randomized controlled studies were searched in PubMed, OvidMedline, Embase (1946 to present). Standard mean difference (SMD), and associated credible interval (CI) were calculated using RevMan statistical software to assess the continuous data. Heterogeneity in studies was measured by I values. Subgroup analysis was performed based on different bone turnover.
RESULTS
A total of 5 randomized controlled studies met the inclusion criteria. Both OPG and RANKL had no significant differences between the osteoporosis and control group, and the statistical heterogeneity was high in meta-analysis. However, RANKL had significant differences between the osteoporosis group with low bone turnover and control group (SMD = - 1.17; 95% CI - 1.77 to 0.57; P value < 0.01) in subanalysis. Furthermore, the OPG/RANKL ratio was significant lower in the osteoporosis group than in the control group (SMD = - 0.29; 95% CI - 0.57 to - 0.02; P value < 0.05), and the statistical heterogeneity was very low (Chi = 0.20, P = 0.66, I = 0%).
CONCLUSIONS
Our meta-analysis study supported OPG and RANKL were important modulatory factors of bone formation and resorption in bone turnover, respectively. Although the serum level of both OPG and RANKL were not associated with osteoporosis, but the OPG/RANKL ratio was associated with osteoporosis. In future, standardizing the test method and unit was good to clinical application.
Topics: Humans; Osteoprotegerin; Osteoporosis; Bone Remodeling; Osteogenesis; RANK Ligand; Bone Density
PubMed: 37932757
DOI: 10.1186/s13018-023-04179-5 -
Journal of Indian Prosthodontic Society 2023The aim of this study was to analyze the induction effect of a combination of N. sativa and bovine bone graft on the expression and ratio of receptor activator of...
Expression and ratio of receptor activator of nuclear factor kappa-B ligand and osteoprotegerin following application of /bovine bone graft combination in post tooth extraction sockets.
AIMS
The aim of this study was to analyze the induction effect of a combination of N. sativa and bovine bone graft on the expression and ratio of receptor activator of nuclear factor kappa-B ligand expression (RANKL) and osteoprotegerin (OPG) on alveolar bone socket preservation on days 7 and 14.
SETTINGS AND DESIGN
The research incorporated a posttest-only control group design. A total of 56 Cavia cobaya were divided into four groups: a control group, an N. sativa group, a bovine bone graft group, and a combined N. sativa and bovine bone graft group.
MATERIALS AND METHODS
The lower incisors of the C. cobaya were extracted with material subsequently being applied to the resulting socket. After the 7 and 14 days, the experimental animals were terminated to enable observation of the socket. Following processing, the tissue was subjected to immunohistochemistry staining consisting of RANKL and OPG antibodies before being observed under a light microscope at × 400.
STATISTICAL ANALYSIS USED
Statistical analysis was carried out using the one-way ANOVA and Tukey's honestly significant difference tests.
RESULTS
A combination of N. sativa and bovine bone graft reduced both RANKL expression and the RANKL/OPG ratio while increasing OPG expression in comparison to the other groups. In all the results obtained, the N. sativa and bovine bone graft combination was significant (P < 0.05) when compared to the control group on both the 7 and 14 days.
CONCLUSION
A combination of N. sativa and bovine bone graft reduced both RANKL expression and the RANKL/OPG ratio while increasing OPG expression.
Topics: Animals; Cattle; Guinea Pigs; Osteoprotegerin; Receptor Activator of Nuclear Factor-kappa B; NF-kappa B; Nigella sativa; Ligands; Tooth Extraction; RANK Ligand
PubMed: 37929367
DOI: 10.4103/jips.jips_198_23 -
Medicina (Kaunas, Lithuania) Oct 2023: Osteoprotegerin (OPG), a soluble glycoprotein found in serum, has been associated with both the presence and severity of atherosclerosis. OPG is regarded as the...
: Osteoprotegerin (OPG), a soluble glycoprotein found in serum, has been associated with both the presence and severity of atherosclerosis. OPG is regarded as the mediator in the process of vascular endothelial dysfunction. Impaired endothelial function has an intimate link with hypertension (HTN) and is associated with significant morbidity and mortality. This study was to investigate the connection between OPG and endothelial dysfunction in patients having HTN. : There are 102 patients with HTN included. For the purpose of determining the levels of OPG, a commercial enzyme-linked immunosorbent test kit was applied. The vascular reactivity index (VRI), which is assessed via the digital thermal monitoring, provides information on endothelial function. : Ten patients with HTN (9.8%) were classified as having poor vascular reactivity (VRI < 1.0), 46 HTN patients (45.1%) as having intermediate vascular reactivity (1.0 ≤ VRI < 2.0), and 46 HTN patients (45.1%) were classified as having high vascular reactivity (VRI ≥ 2.0). A greater serum OPG level ( < 0.001) and older age ( = 0.022) were linked to impaired vascular reactivity. The estimated glomerular filtration rate ( = 0.196, = 0.048) was positively correlated with VRI values in hypertensive participants, while advanced age ( = -0.222, = 0.025) and the log-transformed OPG level (log-OPG, = -0.357, < 0.001) were negatively correlated with VRI. Serum log-OPG level was shown to be strongly and independently correlated with VRI values in HTN individuals after multivariable forward stepwise linear regression analysis (β = -0.357, adjusted R change = 0.119, < 0.001). : In patients with HTN, serum OPG levels were adversely correlated with VRI and probably had a role in endothelial dysfunction.
Topics: Humans; Osteoprotegerin; Hypertension; Regression Analysis; Linear Models; Atherosclerosis; Biomarkers
PubMed: 37893512
DOI: 10.3390/medicina59101794 -
Biomedicines Aug 2023Individuals with inflammatory bowel disease (IBD) have an increased risk of bone impairment, which is a process controlled by the RANKL/RANK/OPG system, mostly due to...
UNLABELLED
Individuals with inflammatory bowel disease (IBD) have an increased risk of bone impairment, which is a process controlled by the RANKL/RANK/OPG system, mostly due to chronic inflammation and corticosteroid treatment. Bone morphogenic protein 7 (BMP7) has a complex role in maintaining inflammation and bone remodeling but little is known about its anti-inflammatory potential in chronic colitis. We investigated the effect of systemically administered BMP7 and corticosteroids on the severity of inflammation, macrophage differentiation, and bone regeneration in a chronic IBD model.
METHODS
Chronic colitis was induced in male Sprague Dawley rats via weekly administration of 2,4,6-trinitrobenzenesulfonic acid over 21 days following BMP7 or corticosteroid treatment for five days. The levels of serum and colon tissue inflammatory cytokines, RANKL/OPG system, as well as markers of macrophage polarization, were detected using RT-PCR, ELISA, or immunohistochemistry. Long bone and spine analyses were performed using microcomputed tomography (micro-CT).
RESULTS
The administration of BMP7 reduced the adverse effects of colitis and led to elevated OPG and RANK in the colon with a simultaneous decrease in TNF-α and an increase in IL-10 and TGF-β. Decreased expression of the M2 macrophage marker CD163 was found in the BMP7-treated rats compared with the colitis group, whereas the number of M1 marker iNOS-positive cells did not differ between the groups. As a result of the BMP7 treatment, morphometric parameters of trabecular bone increased, and increased trabecular separation noted in the colitis group did not appear.
CONCLUSIONS
We showed that BMP7 suppressed the inflammatory response in chronic colitis, mainly by shifting the cytokine balance and by triggering alterations in the RANKL/OPG system rather than through a macrophage polarization imbalance. In addition, considering the demonstrated effect of BMP7 on bone morphology and structure, it can be suggested that BMP7 plays a role in the managing of osteoporosis in chronic colitis, and thus, its therapeutic potential in the treatment of IBD should be further evaluated.
PubMed: 37626658
DOI: 10.3390/biomedicines11082161 -
European Journal of Dentistry Feb 2024Tumor necrosis factor-α (TNF-α) causes bone resorption in periodontitis. It induces the production of receptor activator of NF-κB ligand (RANKL) from osteoblasts,...
OBJECTIVES
Tumor necrosis factor-α (TNF-α) causes bone resorption in periodontitis. It induces the production of receptor activator of NF-κB ligand (RANKL) from osteoblasts, leading to the disturbance of bone homeostasis through RANKL, RANK, and osteoprotegerin (OPG) axis. This study aimed to explore the effect of periodontal ligament stem cells-derived conditioned medium (PDLSCs-CM) on gene expression related to bone homeostasis and the differentiation of TNF-α-challenged osteoblasts.
MATERIALS AND METHODS
Human osteoblasts were cultured with 50 ng/mL of TNF-α and 0, 1, 10, and 100 µg/ mL of PDLSCs-CM. Osteoblasts cultured without TNF-α and PDLSCs-CM were served as control. Gene expression of RANKL, OPG, and interleukin-1β (IL-1β) was evaluated by reverse transcription quantitative polymerase chain reaction at 48 hours. The early-stage and late-stage differentiation of TNF-α-challenged osteoblasts without or with PDLSCs-CM was explored by alkaline phosphatase (ALP) activity and alizarin red staining, respectively, at day 1, 3, 6, 9, and 12.
STATISTICAL ANALYSIS
Mann-Whitney U test was used to analyze the differences in gene expression of TNF-α-challenged osteoblasts at 24 and 48 hours, and Kruskal-Wallis test was used to analyze the effect of PDLSCs-CM on gene expression and ALP activity among all experimental groups using SPSS software version 21.0. Statistical significance was considered with -value less than 0.05.
RESULTS
Expression of RANKL, OPG and IL-1β was significantly upregulated in TNF-α-challenged osteoblasts compared to the untreated control. The PDLSCs-CM at 1 and 10 μg/mL downregulated gene expression of TNF-α-challenged osteoblasts compared to the group without PDLSCs-CM, but the difference did not reach statistical significance. The ALP activity was decreased in TNF-α-challenged osteoblasts. The addition of PDLSCs-CM did not alter ALP activity of TNF-α-challenged osteoblasts. Alizarin red staining was comparable in the TNF-α-challenged osteoblasts cultured without or with PDLSCs-CM.
CONCLUSIONS
The PDLSCs-CM did not alter gene expression involved in bone homeostasis and differentiation of TNF-α-challenged osteoblasts.
PubMed: 37562430
DOI: 10.1055/s-0043-1771337 -
ESC Heart Failure Oct 2023The aim of this study was to determine microvascular function in the acute phase of Takotsubo syndrome (TTS) and to identify inflammatory mediators that could reflect...
AIMS
The aim of this study was to determine microvascular function in the acute phase of Takotsubo syndrome (TTS) and to identify inflammatory mediators that could reflect TTS-induced pathology.
METHODS AND RESULTS
The study included 20 females [median age 65 years; interquarile range (IQR) = 58-70 years] with TTS according to the Mayo diagnostic criteria. During heart catheterization, we determined the index of microvascular resistance (IMR) and drew blood samples almost simultaneously from the aorta and coronary sinus. Cardiac magnetic resonance imaging (MRI) was done in the acute phase. We present descriptive coronary physiology and cardiac MRI data and compare inflammatory biomarkers between samples from the aorta, coronary sinus, and venous samples after 3 months using the Wilcoxon signed-rank test. For comparison, we also analysed the actual biomarkers in venous blood from 15 healthy female controls. A supplementary analysis explored Spearman's rank correlation between the inflammatory biomarkers, IMR, MRI data, and cardiac biomarkers. The median IMR was 16.5 mmHg·s (IQR = 10.5-28.2 mmHg·s), which was only slightly higher than that in the reference populations. Seven (35%) of the study subjects had IMR > 25 mmHg·s, suggesting a microvascular dysfunction. IMR was not affected by time from symptom onset. According to MRI, the apical region of the left ventricle was affected in 65% of the subjects. The median ejection fraction was 41% (IQR = 31-48%). Biomarker analyses revealed elevation of markers for extracellular matrix remodelling and fibrosis, inflammation, immune activation, and upstream inflammation as compared with healthy controls. Only the levels of interleukin (IL)-1 receptor antagonist and soluble T-cell immunoglobulin mucin domain-3 (sTIM-3) were higher in the coronary sinus than in the aorta. No variable was significantly correlated with IMR. The IL-6 level in the aorta was inversely correlated with the left ventricular ejection fraction. Growth differentiation factor-15, osteoprotegerin, and von Willebrand factor levels in both aorta and coronary sinus were positively correlated with N-terminal-pro-brain-natriuretic peptide, while the correlations of IL-6 and sTIM-3 with N-terminal-pro-brain-natriuretic peptide were restricted to the aorta and coronary sinus, respectively. While most of the markers were within normal limits after 3 months, matrix metalloproteinase-9 increased during follow-up to reach levels higher than those in the healthy controls.
CONCLUSION
The median IMR was only slightly elevated in this study, but about one-third of the patients had values indicating microvascular dysfunction. The present study supports the involvement of several inflammatory pathways in TTS, including monocyte/macrophage activation, with sTIM-3 as a potential novel marker.
PubMed: 37537779
DOI: 10.1002/ehf2.14461