Osteoprotegerin Levels Research Articles

Pathogenetic Role of Osteoprotegerin and Osteopontin in the Development of Cardiovascular Complications in Comorbid Pathology

This study investigated the pathogenetic role of osteoprotegerin (OPG) and osteopontin (OPN) in the development of cardiovascular complications and osteoporotic fractures in women with chronic heart failure (CHF), osteoporosis, and type 2 diabetes mellitus (T2DM). A total of 150 postmenopausal women participated in the study. The serum levels of OPG and OPN were assessed, along with their relationship with the frequency of adverse cardiovascular events (CVE) and osteoporotic fractures. It was found that patients with elevated OPG levels (>50 mmol/L) had a significantly higher rate of CVE (65%) compared to those with lower levels. Increased OPN levels (>250 ng/mL) were associated with a rise in osteoporotic fractures, reaching up to 60%. Patients with high levels of both biomarkers showed the highest risk for both cardiovascular events and fractures. Statistical analysis revealed a strong correlation between OPG levels and CVE frequency (r=0.62, p<0.001), as well as between OPN levels and fracture frequency (r=0.58, p<0.001). These results highlight the critical role of OPG and OPN in the pathogenesis of comorbid conditions and their potential clinical significance as markers for predicting complication risks. The identified relationships could be used to develop new diagnostic and preventive strategies for cardiovascular and osteoporotic complications in patients with comorbid pathologies.

New atherosclerosis progression markers in patients with post-Chernobyl metabolic syndrome

Relevance. As an epidemiologically proven consequence of the Chernobyl NPP accident, circulatory diseases are among the leading morbidities in liquidators. To predict the development of adverse cardiovascular events in patients with metabolic syndrome, there is the ongoing search for informative laboratory markers.The objective is to show how osteopontin, osteoprotegerin, fetuin-A, and risk factors for genetic circulatory disorders are associated with traditional risk factors for circulatory disorders in Chernobyl nuclear power plant accident liquidators suffering metabolic syndrome. Another objective is to explore the perspectives to use these indicators to forecast coronary atherosclerosis progression.Methods. The study group included 50 male liquidators of the Chernobyl nuclear power plant accident who suffered metabolic syndrome. The patients were split in two groups depending on osteopontin concentration in blood serum, i.e. above or under the upper reference limit. Medical history data, biochemical parameters, including inflammatory proteins, osteoprotegerin, fetuin-A, and genotyping of polymorphic variants of genes associated with the risk of circulatory diseases were analyzed. A control group of 30 conditionally healthy men was formed to determine the normal osteopontin, osteoprotegerin and fetuin-A values in blood serum.Results and discussion. With osteopontin value exceeding 21.4 ng/mL, the liquidators’ medical history showed 1.5 times higher frequency of myocardial infarction, 2.5 times higher frequent history of acute cerebral circulation disorder; ischemic heart disease was associated with type 2 diabetes mellitus. It was shown that the group of liquidators (osteopontin over 21.4 ng/ml) was characterized by a reliable increase in atherogenicity coefficient and osteoprotegerin level. Meanwhile, when compared to the control group, the same group of patients showed lower fetuin-A values and elevated high-sensitivity C-reactive protein, homocysteine, leptin and ghrelin. It was found that in liquidators, the presence of the A allele in the vitamin B12-dependent methionine synthase (MTR) gene (2756 A>G) is associated with more pronounced biochemical markers of atherosclerosis progression compared to GG genotype carriers.Conclusion. Osteopontin performs a protective role in tissue damage, being is practically undetectable in normal conditions. However, in case of pathology its value increases dramatically. In patients with metabolic syndrome, decreased fetuin-A and osteopontin values exceeding 21.4 ng/mL require additional examination with a focus on cardiovascular pathology (coronary artery calcinosis), as well as a dual-energy X-ray absorptiometry to ensure early detection of diminished bone mineral density and body mass. It was found that in liquidators, the presence of A-allele (genotypes AA and AG) in the MTR 2756 A>G gene is characterized by deeper atherogenic changes in the lipid spectrum, increased atherogenicity coefficient and decreased adiponectin content. This justifies the need for genotyping to build individual forecast for atherosclerosis progression in this category of patients.

Osteoprotegerin secretion and its inhibition by RANKL in osteoblastic cells visualized using bioluminescence imaging

Bone remodeling is regulated by the interaction between receptor activator of nuclear factor kappa-B ligand (RANKL) and its receptor RANK on osteoblasts and osteoclasts, respectively. Osteoprotegerin (OPG) is secreted from osteoblasts and inhibits osteoclast differentiation by acting as a decoy receptor for RANKL. Despite its importance, the mechanism underlying the secretion of OPG remains poorly understood. Here, we applied a method of video-rate bioluminescence imaging using a fusion protein with Gaussia luciferase (GLase) and visualized the secretion of OPG from living mouse osteoblastic MC3T3-E1 cells. The bioluminescence imaging revealed that the secretion of OPG fused to GLase (OPG-GLase) occurred frequently and widely across the cell surface. Notably, co-expression of RANKL significantly reduced the secretion of OPG-GLase, indicating an inhibitory role of RANKL on OPG secretion within cells. Further imaging and biochemical analyses using deletion mutants of OPG and RANKL, as well as RANKL mutants that cause autosomal recessive osteopetrosis, demonstrated the essential role of protein-protein interaction between OPG and RANKL in the inhibition of OPG secretion. Treatment with proteasome inhibitors resulted in increased levels of OPG in both culture medium and cell lysates. However, the fold-increase of OPG was similar regardless of the presence or absence of RANKL, suggesting that the regulation of OPG secretion by RANKL is independent of proteasome activity. This report visualized the secretion of OPG from living cells and provided evidence for a novel intracellular inhibitory effect of RANKL on OPG secretion.

An antibody nanopore-enabled microsensor for detection of osteoprotegerin

This paper introduces an antibody-based nanopore thin film sensor for detecting osteoprotegerin (OPG) in buffer solutions and serum samples, offering significant improvements over current commercial enzyme-linked immunosorbent assay kits in terms of cost, specificity, and selectivity. Capable of detecting OPG concentrations as low as 0.25 pg ml−1—far below the limits of traditional lab equipment—this sensor requires only about 1 μl of serum for effective measurement. The utilization of reference sensors helps reduce non-specific binding, enhancing the sensor’s accuracy. Its affordability and operational simplicity make it ideal for point-of-care monitoring of OPG levels in real-time patient care.

The effects of photobiomodulation and/or azithromycin treatment on bone resorption biomarkers in gingival crevicular fluid from patients with stage III-IV grade C periodontitis.

This study aims to investigate the impact of photobiomodulation (PBM) and/or azithromycin (AZM) therapy in combination with full-mouth subgingival instrumentation (FSI) on receptor activator of nuclear factor κB ligand (RANKL) and osteoprotegerin (OPG) levels and RANKL/OPG ratios in gingival crevicular fluid (GCF) on patients with stage III-IV grade C periodontitis. The study was conducted on 77 stage III-IV grade C periodontitis patients and 20 periodontally healthy controls. Patients with stage III-IV grade C periodontitis were categorized into four treatment groups: 1) only FSI (FSI) group; 2) FSI&#43;AZM (AZM) group; 3)FSI&#43;PBM (PBM) group and 4) FSI&#43;PBM&#43;AZM (AZM&#43;PBM) group. Clinical periodontalparameters and RANKL and OPG levels and RANKL/OPG ratios in GCF were measured at thebaseline and month 3rd of the therapy. Compared with the periodontally healthy controls,all the baseline clinical parameters were higher in the Stage III-IV grade C periodontitis groups (P< 0.05); however, there were no statistically significant differences between the Stage III-IV gradeC periodontitis groups (P>0.05). In month 3rd, the lowest values in all clinical parameters weregenerally observed in the antibiotics groups whereas the highest values were observed in the FSIgroup. Furthermore, the highest RANKL and OPG values in antibiotic groups and the highestRANKL/OPG ratio in PBM group were observed in the third months. RANKL/OPG ratios did notchange in the FSI and antibiotics groups after the treatment, but it increased significantly in thePBM group. While PBM treatment combined with FSI increases the RANKL levels,AZM increases OPG levels. Also, PBM&#43;AZM treatment shows additional clinical andimmunological beneficial efficacy.

Non-classical monocyte levels correlate negatively with HIV-associated cerebral small vessel disease and cognitive performance.

Despite antiretroviral treatment (cART), aging people living with HIV (PWH) are more susceptible to neurocognitive impairment (NCI) probably due to synergistic/additive contribution of traditional cerebrovascular risk factors. Specifically, transmigration of inflammatory CD16+ monocytes through the altered blood brain barrier (BBB) may exacerbate cerebral small vessel disease (CSVD), a known cause of vascular cognitive impairment. PWH on cART (n=108) and age, sex, and Reynold's cardiovascular risk score-matched uninfected individuals (PWoH, n=111) were enrolled. This is a longitudinal observational study but only cross-sectional data from entry visit are reported. Neuropsychological testing and brain magnetic resonance imaging (MRI) were performed. CSVD was diagnosed by Fazekas score ≥1. Flow cytometric analyses of fresh whole blood were conducted to evaluate circulating levels of monocyte subsets (classical, intermediate, and non-classical) and markers of monocyte activation (CCR2, CD40, PSGL-1, TNFR2 and tissue factor). ELISAs were used to measure sCD14, ICAM, and Osteoprotegerin. Two-way analysis of variance (ANOVA), and linear regression models were performed to study the effects of HIV status, CSVD status, and their interaction to outcome variables such as cognitive score. Two-sample t-tests and correlation analyses were performed between and within PWoH with CSVD and PWH with CSVD participants. PWH with CSVD (n=81) had significantly lower total cognitive scores, higher levels of NCMs and soluble CD14 and intracellular adhesion molecule 1 (ICAM-1) as compared to PWoH with CSVD group (n=68). sCD14 and ICAM1 were positively correlated with each other indicating that monocyte and endothelial activation are associated with each other. Cognition was negatively correlated with NCMs, especially in the PWH with CSVD group. Among other blood biomarkers measured, osteoprotegerin levels showed mild negative correlation with cognitive performance in individuals with CSVD irrespective of HIV status. Elevated levels of NCMs may contribute to neuroinflammation, CSVD and subsequent cognitive impairment. This finding is of particular relevance in aging PWH as both HIV and aging are associated with increased levels of NCMs. NCMs may serve as a potential biomarker to address these comorbidities. Further longitudinal studies are needed to evaluate whether changes in NCM levels are associated with changes in CSVD burden and cognitive impairment.

Exploring the Impact of Catechins on Bone Metabolism: A Comprehensive Review of Current Research and Future Directions.

Background/Objectives: Degenerative musculoskeletal diseases represent a global health problem due to the progressive deterioration of affected individuals. As a bioactive compound, catechins have shown osteoprotective properties by stimulating osteoblastic cells and inhibiting bone resorption. Thus, this review aimed to address the mechanism of action of catechins on bone tissue. Methods: The search was applied to PubMed without limitations in date, language, or article type. Fifteen articles matched the topic and objective of this review. Results: EGCG (epigallocatechin gallate) and epicatechin demonstrated action on the osteogenic markers RANKL, TRAP, and NF-κβ and expression of BMPs and ALP, thus improving the bone microarchitecture. Studies on animals showed the action of EGCG in increasing calcium and osteoprotegerin levels, in addition to regulating the transcription factor NF-ATc1 associated with osteoclastogenesis. However, it did not show any effect on osteocalcin and RANK. Regarding human studies, EGCG reduced the risk of fracture in a dose-dependent manner. In periodontal tissue, EGCG reduced IL-6, TNF, and RANKL in vitro and in vivo. Human studies showed a reduction in periodontal pockets, gingival index, and clinical attachment level. The action of EGCG on membranes and hydrogels showed biocompatible and osteoinductive properties on the microenvironment of bone tissue by stimulating the expression of osteogenic growth factors and increasing osteocalcin and alkaline phosphate levels, thus promoting new bone formation. Conclusions: EGCG stimulates cytokines related to osteogenes, increasing bone mineral density, reducing osteoclastogenesis factors, and showing great potential as a therapeutic strategy for reducing the risk of bone fractures.

Therapeutic effect of Micro-Implant Anchorage in orthodontics

Objective: Micro implant anchorage (MIA), as a new orthodontic treatment technique, has the characteristics of simple operation, light trauma, and high stability, and has been widely used in clinical practice. This study compared the therapeutic effects of MIA and the traditional straight wire appliance (SWA) in orthodontic practice. Methods: Clinical data of 119 patients who underwent orthodontic treatment in Yulin First Hospital from January 2022 to January 2023 were retrospectively analyzed. According to the treatment records, 61 patients received MIA orthodontic treatment (MIA group), and 58 patients received traditional straight wire appliance (SWA) orthodontic treatment (SWA group). Treatment effect, periodontal index, and levels of osteoprotegerin (OPG), interleukin-6 (IL6) and high-sensitivity C-reactive protein (hsCRP) of the two groups were compared. Results: The total efficacy of MIA group was significantly higher than that of SWA group (P&lt;0.05). After the treatment, bleeding index (BI), plaque index (PLI), probing depth (PD) and looseness in the MIA group were significantly lower than those in the SWA group (P&lt;0.05). After the treatment, levels of OPG were significantly higher, while IL6 and hsCRP levels were significantly lower in the MIA compared to the SWA group (P&lt;0.05). MIA was associated with significantly lower complication rate compared to the SWA (P&lt;0.05). Conclusions: Compared with SWA, MIA is associated with better orthodontic effect. This mode of treatment can increase OPG levels, reduce inflammation, and lower the risk of complications. doi: https://doi.org/10.12669/pjms.40.10.10442 How to cite this: Shi Y, Mi L, Liu J, Liu X, Hao Y. Therapeutic effect of Micro-Implant Anchorage in orthodontics. Pak J Med Sci. 2024;40(10):2293-2298. doi: https://doi.org/10.12669/pjms.40.10.10442 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Antiosteoporosis and bone protective effect of alpinumisoflavone in steroid-induced osteoporosis rats via alteration of apoptosis, inflammatory and RANK/RANKL/OPG signaling pathway

Objective: To estimate the bone protective effect of alpinumisoflavone, a natural prenylated isoflavonoid, against glucocorticoid-induced osteoporosis in rats. Methods: Male Wistar rats received intramuscular administration of dexamethasone (4 mg/mL) at a dose level of 7 mg/kg for 5 weeks, and then alpinumisoflavone (5, 10, and 15 mg/kg) and alendronate (2 mg/kg) from 2 weeks. The body weight and organ weight (femoral, vagina, and uterus) were estimated. MicroCT analysis, bone turnover markers, bone parameters, oxidative stress parameters, and inflammatory cytokines were estimated. mRNA expressions of related genes were also estimated. Results: Alpinumisoflavone remarkably boosted body weight and organ weight (ureters and vagina), improved microCT analysis parameters, and boosted levels of bone markers. Besides, alpinumisoflavone considerably (P&lt;0.001) restored the level of bone turnover markers and oxidative stress parameters, remarkably suppressed the level of cytokines such as interleukin-1β, interleukin-6, tumor necrosis factor-α, and increased transforming growth factor-β and insulin-like growth factor. It also significantly restored the osteoprotegerin (OPG, RANKL, and OPG/RANKL ratio) levels and the mRNA expression of Caspase (3, 6, 7, 9), BMPs, OPN, ALP, RUNX2, and OCN. Conclusions: The current result suggests the bone protective effect of alpinumisoflavone against glucocorticoid-induced osteoporosis in rats.

Association of periodontitis with serum osteoprotegerin level in type 2 diabetic postmenopausal women.

To evaluate the association of periodontitis with serum osteoprotegerin level according to glycaemic state in postmenopausal type 2 diabetic women. The case-control study was conducted from June 2019 to May 2020 at the National Diabetes Centre, Mustansiriyah University, Baghdad, Iraq, and comprised postmenopausal diabetic women with good glycaemic control in group A, diabetic women with poor glycaemic control in group B, and non-diabetic healthy controls in group C. Participants were inducted by using the consecutive sampling technique. Assessment of periodontitis was done by measuring probing pocket depth, gingival recession and clinical attachment level. The ratio between serum osteoprotegerin level and glycated haemoglobin was calculated for all the subjects. Data was analysed using SPSS 24. Of the 150 subjects, 57(38%) were in group A with mean age 57.39±5.89 years, 43(28.7%) were in group B with mean age 58.91±4.95 years, and 50(33.3%) were in group C with mean age 54.92±4.62 years. Probing pocket depth, clinical attachment level and serum osteoprotegerin exhibited higher values in groups A and B compared to group C, and in group B compared to group A (p<0.001). There was a significant positive correlation between Probing pocket depth and serum osteoprotegerin in all groups (p<0.05). Periodontal parameters and serum osteoprotegerin level were significantly higher in diabetic women, especially in those with poor glycaemic control, than in healthy controls, and serum osteoprotegerin level showed a significant positive correlation with probing pocket depth in all the studied groups.

Beneficial effects of IVIG treatment on experimental-induced osteoporosis.

Estrogen (E2) plays a significant role in postmenopausal osteoporosis, and its deficiency is related to chronic low-grade inflammation. Intravenous immunoglobulin (IVIG) is composed of immunoglobulins derived from the plasma of healthy donors. Numerous anti-inflammatory pathways are responsible for IVIG's anti-inflammatory action The aim of this study is to investigate the effects of IVIG on experimental-induced osteoporosis. Forty adult female Wistar rats were included in the study. Thirty rats underwent bilateral dorsal ovariectomy. Rats were grouped as Group 1 (n = 10, ovariectomy and saline); Group 2 (n = 10, ovariectomy and E2); Group 3 (n = 10, ovariectomy and IVIG), and Control group (n = 10, no oophorectomy). Histopathological examination of bone tissue, and biochemical analysis for beta-catenin, plasma Tumor Necrosis Factor-α, IL-6, receptor activator of nuclear-κB ligand (RANKL), and osteoprotegerin (OPG) levels were made. The IVIG group had increased trabecular number, area, and thickness with increased bone mineral density as well as decreased trabecular separation compared with the saline group. IVIG group had lower serum RANKL and higher serum OPG levels when compared with the saline group. The bone marrow beta-catenin level was significantly higher in the control and ovariectomy + IVIG groups. IVIG has beneficial effects on experimentally induced osteoporosis with a possible action on inflammation and RANKL-β-catenin pathway.

Vertebral marrow fat fraction is associated with circulating RANKL in postmenopausal females.

To investigate the relationship between circulating receptor activator of nuclear factor-kappa B ligand (RANKL) levels and marrow adipose tissue in postmenopausal females. A total of 164 postmenopausal females were included in the study. Serum levels of osteoprotegerin (OPG) and RANKL were measured using ELISA kits. Body composition and bone mineral density (BMD) were assessed using dual-energy X-ray absorptiometry. Complex-based chemical shift imaging-based MRI was employed to evaluate the vertebral marrow proton density fat fraction (PDFF). A multivariate linear regression model was utilized to analyze the predictive effects of PDFF and BMD on circulating levels of OPG and RANKL. Simple regression analysis showed significant associations among the marrow PDFF, BMD at either site, serum RANKL, and the RANKL/OPG ratio. In multivariate linear regression models, marrow PDFF was found to have a positive correlation (β = 3.15, 95% CI 2.60 to 3.70) and BMD had negative correlations (β = -0.200, 95% CI -0.348 to -0.051 for vertebral BMD; β = -0.383, 95% CI -0.589 to -0.177 for total hip BMD; and β =-0.393, 95% CI -0.598 to -0.188 for femoral neck BMD, all p < 0.01) with circulating soluble RANKL levels after adjusting for age, body mass index, physical activity, total fat mass, android/gynoid ratio, and lean mass. Similar results were observed for the RANKL/OPG ratio. Additionally, multivariate linear regression analyses revealed that marrow PDFF was a significant independent contributor of circulating soluble RANKL (β = 1.34, 95% CI 1.10 to 1.58, p < 0.001) after further controlling for BMD. However, marrow PDFF or BMD had no associations with circulating levels of OPG after adjusting for all potential confounders mentioned above. Vertebral marrow fat fraction is independently associated with circulating soluble RANKL levels in postmenopausal females.

Vascular Cytokines and Atherosclerosis: Differential Serum Levels of TRAIL, IL-18, and OPG in Obstructive Coronary Artery Disease.

The risk-factor-based prediction of atherosclerotic coronary artery disease (CAD) remains suboptimal, particularly in the absence of any of the standard modifiable cardiovascular risk factors (SMuRFs), making the discovery of biomarkers that correlate with atherosclerosis burden critically important. We hypothesized that cytokines and receptors associated with inflammation in CAD-tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), interleukin-18 (IL-18), and osteoprotegerin (OPG)-would be independently associated with CAD. To determine this, we measured the serum biomarker levels of 993 participants from the BioHEART study who had CT coronary angiograms that were scored for severity of stenosis and plaque composition. We found that the quartiles of TRAIL, OPG, and IL-18 were significantly associated with disease scores, and that the IL-18/TRAIL and OPG/TRAIL ratios demonstrated significant differences between no CAD vs. STEMI whereas only the OPG/TRAIL ratio showed differences between no CAD and obstructive CAD (stenosis > 50%). However, these associations did not persist after adjustment for age, sex, SMuRFs, and a family history of CAD. In conclusion, TRAIL, IL-18, and OPG and the derived ratios of IL-18/TRAIL and OPG/TRAIL demonstrate significant associations with raw disease scores and risk factors, but these markers are not discriminatory biomarkers for the prediction of CAD when incorporated into multi-variable risk models.

Inflammation and Vitamin D Receptor Polymorphism: Impact on All-Cause and Cardiovascular Mortality in Mexican Women on Dialysis.

Mineral bone disease (MBD) is common in dialysis patients. Genetics and the hormonal environment influence the clinical picture and outcomes of women. This study aimed to determine how these factors affect mortality. In 234 female dialysis patients on Continuous Ambulatory (48%) or Automated (29%) Peritoneal Dialysis or Hemodialysis (23%), MBD biochemical variables, as well as bone density and genetic Bsm1 polymorphism of vitamin D receptor (VDR) were performed at baseline. The cohort was followed-up by 17 (IQ range 15-31) months. According to VDR polymorphism, the distribution of patients was bb: 64% and BB+Bb: 36%. Fifty-five patients died from all-cause mortality; the hs-C-reactive protein level was the most significant risk in multivariate Cox analysis. Nineteen died from cardiovascular mortality. None of the variables were significant for cardiovascular mortality. Patients with bb plus inflammation had the highest risk in the analysis; the significance persisted after adjustment for age, diabetes, and parathyroid hormone levels HR 2.33 (95% CI, 1.01-8.33) and after further adjustment for time on dialysis, albumin, and Osteoprotegerin levels HR 3.49 (95% CI, 1.20-10.9). The presence of the bb genotype from VDR and inflammation had the highest risk of death from all-cause mortality in females on CAPD, APD, and HD patient.

Gingerol nanoparticles attenuate complete Freund adjuvant-induced arthritis in rats via targeting the RANKL/OPG signaling pathway.

Rheumatoid arthritis (RA) is characterized by inflammatory joint pathology leading to the degradation of articular bone and cartilage, primarily triggered by synovial inflammation, resulting in joint discomfort. The metacarpophalangeal and proximal interphalangeal joints are predominantly affected. Treatment typically involves a combination of biological and synthetic disease-modifying antirheumatic drugs (DAMARDs) alongside steroid therapy. The application of nanomedicine has been instrumental in enhancing treatment efficacy by facilitating controlled release of pharmacologically active compounds, thus augmenting bioavailability and enabling targeted drug delivery. Gingerol, a constituent of ginger, possesses multifaceted properties. including anti-inflammatory, anti-oxidant, antidiabetic, and antipyretic effects. In this study, gingerol-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), coated with chitosan, were administered orally to rats over a period of 21days to address RA induced by complete Freund adjuvant (CFA). The rats were segregated into four experimental groups. Upon completion of the treatment regimen, blood samples were collected for the assessment of cyclooxygenase-2 (COX-2), RA factor, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). Subsequent gene expression analysis was conducted to evaluate the levels of interleukin-4 (IL-4), interleukin-17a (IL-17a), IL-6, interferon-gamma (INF-γ), TNF-α, interleukin-1 beta (IL-1β), osteoprotegerin (OPG), and receptor activator of nuclear factor kappa-B ligand (RANKL). Statistical analyses utilizing one-way ANOVA followed by Tukey tests were applied to the data. The gene expression profiling revealed significant disparities in mRNA levels of IL-1β, IL-6, IL-4, IL-17a, RANKL, INF-γ, and TNF-α between the CFA-induced arthritis group and the control group. Consequently, it was inferred that gingerol-loaded PLGA NPs coated with chitosan exhibited heightened therapeutic efficacy in addressing CFA-induced arthritis in rats.

Efficacy of Recombinant Human Parathyroid Hormone 1-34 and Vitamin K2 Combination Therapy in Postmenopausal Osteoporosis.

This study aimed to assess the efficacy and safety of a combined recombinant human parathyroid hormone 1-34 [rhPTH (1-34)] and vitamin K2 therapy versus vitamin K2 alone in the treatment of postmenopausal osteoporosis. A total of 77 postmenopausal osteoporosis patients were randomly divided into two groups. Patients in one group received vitamin K2 alone, while patients in the other group received a combination of rhPTH (1-34) and vitamin K2. Bone mineral density (BMD), electrolyte levels, pain scores, bone metabolism levels, and adverse drug reactions were compared pre- and post-treatment. Both two treatments improved BMD, blood calcium concentrations, pain scores, and increased osteocalcin and osteoprotegerin levels. Notably, the combined rhPTH (1-34) and vitamin K2 treatment demonstrated superior efficacy in improving BMD and bone metabolism markers. Furthermore, there was no significant difference in the incidence of adverse reactions between the two groups, indicating the safety of the combined treatment. In summary, the combined therapy of rhPTH (1-34) and vitamin K2 exhibited more potent efficacy in the treatment of postmenopausal osteoporosis, more effectively enhancing BMD and bone metabolism markers than vitamin K2 alone, without a significant increase in adverse reactions.

Accuracy of Gingival Crevicular Fluid Biomarkers of MMP8, TIMP1, RANK, RANKL, and OPG in Differentiating Symptomatic and Asymptomatic Apical Periodontitis.

Apical periodontitis (AP) is the most prevalent chronic inflammatory disease of the teeth. Bone resorption dynamics in symptomatic and asymptomatic AP are still unrecognized. This study examined different inflammatory markers within gingival crevicular fluid, including matrix metalloproteinases 8 (MMP8), tissue inhibitors of metalloproteinases 1 (TIMP1), receptor activator of nuclear factor κB (RANK), its ligand (RANKL), and osteoprotegerin (OPG), to be used in comparing symptomatic apical periodontitis (SAP) and asymptomatic apical periodontitis (AAP) versus healthy teeth. Subjects with SAP, AAP, and a control group were recruited and GCF samples were collected by Periopaper strips. Clinical and radiographical measures were used for diagnosing AP. Levels of MMP8, TIMP, RANK, RANKL, and OPG were determined by ELISA and their abilities to discriminate between examined sites were evaluated by receiver operator characteristic (ROC) curves. All examined biomarkers were statistically significant higher (p < 0.05) in SAP than AAP and the control group, apart from RANK. Significant positive correlations (p < 0.05) were identified between all SAP and AAP biomarkers except TIMP1 and RANK in AAP teeth. TIMP1 and OPG exhibited the highest ability to distinguish between SAP and AAP with areas under the curve of 0.824 and 0.763 in comparing SAP and the control group, and 0.732 and 0.73 when comparing AAP and the control group, respectively. Additionally, TIMP1 and OPG showed the highest AUC of 0.778 and 0.747 when SAP and AAP were compared, respectively. This study concluded that GCF levels of TIMP1 and OPG can be used to differentiate between SAP, AAP, and healthy teeth.

Anti-inflammatory, antiosteoporotic, and bone protective effect of hydroxysafflor yellow A against glucocorticoid-induced osteoporosis in rats.

Osteoporosis is a common condition worldwide, affecting millions of people. Women are more commonly affected than men, and the risk increases with age. Inflammatory reaction plays a crucial role in the expansion of osteoporosis. Osteoporosis is characterized by a gradual decline in bone density and bone tissue quality, which increases fragility and raises the risk of fractures. We scrutinized the anti-osteoporosis effect of hydroxysafflor yellow A (HYA) against glucocorticoid-induced osteoporosis (GIOP) in rats. In-silico study was carried out on EGFR receptor (PDBID: 1m17), Estrogen Alpha (PDB id: 2IOG), MTOR (PDB id: 4FA6), RANKL (PDB id: 1S55), and VEGFR2 (PDB id: 1YWN) protein. For this investigation, Sprague-Dawley (SD) rats were used, and they received an oral dose of HYA (5, 10, and 20 mg/kg, b.w.) along with a subcutaneous injection of dexamethasone (0.1 mg/kg/day) to induce osteoporosis. The biomechanical, bone parameters, antioxidant, cytokines, inflammatory, nutrients, hormones, and urine parameters were estimated. HYA treatment significantly suppressed the body weight and altered the organ weight. HYA treatment remarkably suppressed the level of alkaline phosphatase, acid phosphatase, and improved the level of bone mineral density (total, proximal, mild, and dis). HYA treatment restored the level of calcium (Ca), phosphorus (P), estradiol (E2), and parathyroid hormone near to the normal level. HYA treatment remarkably altered the level of biomechanical parameters, antioxidant, cytokines, urine, and inflammatory parameters. HYA treatment altered the level of osteoprotegerin (OPG), receptor activator of nuclear factor kappa beta (RANKL) and RANKL/OPG ratio. The result clearly showed the anti-osteoporosis effect of HYA against GIOP-induced osteoporosis in rats via alteration of antioxidant, cytokines, inflammatory, and bone protective parameters.

Mining Candidate Genes and Identifying Risk Factors for Leg Disease in Broilers: A Mendelian Randomization Study.

Clinical investigations have highlighted disruptions in bone metabolic processes and abnormal fluctuations in serum indicator levels during the onset of leg disease (LD) in broilers. However, the presence of a genetic causal relationship for this association remains undetermined. Therefore, the aim of this study is to discern the risk factors underlying LD development using 1235 sequenced white-feathered broilers. We employed Mendelian randomization (MR) analysis to assess the associations of bone strength (BS), bone mineral density (BMD), tibial bone weight (TBW), tibial bone length (TBL), tibial bone diameter (TBD), bone ash (BA), ash calcium (Ash Ca), ash phosphorus (Ash P), serum calcium (Ca), serum phosphorus (P), serum alkaline phosphatase (ALP), and serum osteoprotegerin (OPG) with the incidence of LD. Compelling evidence underscores a causal link between the risk of developing LD and decreased BMD (odds ratio (OR) = 0.998; 95% CI: 0.983, 0.993; P < 0.001) and narrower TBD (OR = 0.985, 95% CI: 0.975, 0.994, P = 0.002). Additionally, serum OPG concentrations (OR: 0.995, 95% CI: 0.992, 0.999, P = 0.008) were associated with BMD (OR = 0.0078, 95% CI = 0.0043 to 0.0140, P < 0.001), indicating a robust genetic relationship between ALP concentrations (OR: 0.988, 95% CI: 0.984, 0.993, P < 0.001) and TBD (OR = 0.0046, 95% CI = 0.0026, 0.0083, P < 0.001). Moreover, elevated serum Ca (OR: 0.564, 95% CI: 0.487, 0.655, P < 0.001) and P (OR: 0.614, 95% CI: 0.539, 0.699, P < 0.001) levels were associated with a narrower TBD. Elevated serum levels of Ca, P, ALP, and OPG contribute to disturbances in bone metabolism, while decreased BMD and narrower TBD are associated with a greater risk of developing LD in broilers. This discovery elucidates the metabolic risk factors for LD in broilers and could provide information on LDs, such as osteoporosis, in humans.

A transdiagnostic and diagnostic-specific approach on inflammatory biomarkers in eating disorders: A meta-analysis and systematic review

Eating disorders (EDs) are severe mental illnesses with a multifactorial etiology and a chronic course. Among the biological factors related to pathogenesis and maintenance of EDs, inflammation acquired growing scientific interest. This study aimed to assess the inflammatory profile of EDs, focusing on anorexia nervosa, bulimia nervosa, and including for the first time binge eating disorder. A comprehensive research of existing literature identified 51 eligible studies for meta-analysis, comparing levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), osteoprotegerin (OPG), soluble receptor activator of nuclear factor kappa-B ligand (sRANKL), interleukin-1β (IL-1β), and interleukin-10 (IL-10) between patients with EDs and healthy controls (HCs). The systematic review explored other inflammatory biomarkers of interest, which did not meet the meta-analysis criteria. Results revealed significantly elevated levels of TNF-α, OPG, sRANKL, and IL-1β in patients with EDs compared to HCs. Additionally, the results highlighted the heterogeneity of inflammatory state among patients with EDs, emphasizing the need for further research into the association between inflammatory biomarkers and psychopathological correlates. This approach should transcend categorical diagnoses, enabling more precise subcategorizations of patients.Overall, this study contributed to the understanding of the inflammatory pathways involved in EDs, emphasizing potential implications for diagnosis, staging, and targeted interventions.