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International Journal of Cardiology Nov 2023The relationship between circulating osteoprotegerin (OPG) levels and the risk of cardiovascular diseases (CVDs) has been the subject of conflicting results in previous...
PURPOSE
The relationship between circulating osteoprotegerin (OPG) levels and the risk of cardiovascular diseases (CVDs) has been the subject of conflicting results in previous observational and experimental studies. To assess the causal effect of genetically predicted OPG levels on the risk of a wide range of CVDs, we used the Mendelian randomization design.
DESIGN
We initially extracted information of genetic variants on OPG levels and their corresponding effect values from the summary data based on the European ancestry genome-wide association study. Subsequently, we performed two-sample Mendelian randomization analyses to assess the causal effect of genetically predicted OPG levels on CVDs by using inverse variance weighting (IVW), MR-Egger, weighted median, and MR-PRESSO methods. We also conducted sensitivity analyzes as well as complementary analyses with a more relaxed threshold for the exposure genetic instrumental variable (P < 5 × 10) to test the robustness of our results.
RESULTS
Our results indicated that genetically predicted OPG levels causally reduce the risk of atrial fibrillation (IVW OR = 0.84; 95% CI = 0.72-0.98; P = 0.0241), myocardial infarction(IVW OR = 0.89; 95% CI = 0.80-0.98; P = 0.0173) and coronary heart disease (IVW: OR = 0.90; 95% CI = 0.82-0.99; P = 0.0286). Further complementary analyses also confirmed the above results remain robust and we also identified a potential causal association of OPG levels with a reduced risk of hypertensive diseases(IVW OR = 0.94;95% CI = 0.88-1.00; P = 0.0394).
CONCLUSION
This study provides compelling evidence for a causal relationship between genetically predicted OPG levels and risk reduction of coronary heart disease, myocardial infarction, and atrial fibrillation, indicating that OPG could potentially serve as a cardiovascular risk marker in clinical practice.
Topics: Humans; Atrial Fibrillation; Cardiovascular Diseases; Genome-Wide Association Study; Mendelian Randomization Analysis; Myocardial Infarction; Osteoprotegerin
PubMed: 37532154
DOI: 10.1016/j.ijcard.2023.131233 -
Journal of Dental Research Aug 2018In lamellar bone, a network of highly oriented interconnected osteocytes is organized in concentric layers. Through their cellular processes contained within canaliculi,... (Review)
Review
In lamellar bone, a network of highly oriented interconnected osteocytes is organized in concentric layers. Through their cellular processes contained within canaliculi, osteocytes are highly mechanosensitive and locally modulate bone remodeling. We review the recent developments demonstrating the significance of the osteocyte lacuno-canalicular network in bone maintenance around implant biomaterials. Drilling during implant site preparation triggers osteocyte apoptosis, the magnitude of which correlates with drilling speed and heat generation, resulting in extensive remodeling and delayed healing. In peri-implant bone, osteocytes physically communicate with implant surfaces via canaliculi and are responsive to mechanical loading, leading to changes in osteocyte numbers and morphology. Certain implant design features allow peri-implant osteocytes to retain a less aged phenotype, despite highly advanced extracellular matrix maturation. Physicochemical properties of anodically oxidized surfaces stimulate bone formation and remodeling by regulating the expression of RANKL (receptor activator of nuclear factor-κB ligand), RANK, and OPG (osteoprotegerin) from implant-adherent cells. Modulation of certain osteocyte-related molecular signaling mechanisms (e.g., sclerostin blockade) may enhance the biomechanical anchorage of implants. Evaluation of the peri-implant osteocyte lacuno-canalicular network should therefore be a necessary component in future investigations of osseointegration to more completely characterize the biological response to materials for load-bearing applications in dentistry and orthopedics.
Topics: Animals; Biocompatible Materials; Bone Remodeling; Bone-Implant Interface; Dental Implants; Humans; Osseointegration; Osteocytes; Osteogenesis; Surface Properties
PubMed: 29863948
DOI: 10.1177/0022034518778033 -
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 -
Cells Jul 2023Ageing is associated with cardiovascular disease (CVD). As no single biomarker reflects the full ageing process, we aimed to investigate five CVD- and age-related... (Randomized Controlled Trial)
Randomized Controlled Trial
Effects of an Intervention with Selenium and Coenzyme Q on Five Selected Age-Related Biomarkers in Elderly Swedes Low in Selenium: Results That Point to an Anti-Ageing Effect-A Sub-Analysis of a Previous Prospective Double-Blind Placebo-Controlled Randomised Clinical Trial.
Ageing is associated with cardiovascular disease (CVD). As no single biomarker reflects the full ageing process, we aimed to investigate five CVD- and age-related markers and the effects of selenium and coenzyme Q10 intervention to elucidate the mechanisms that may influence the course of ageing. This is a sub-study of a previous prospective double-blind placebo-controlled randomized clinical trial that included 441 subjects low in selenium (mean age 77, 49% women). The active treatment group (n = 220) received 200 µg/day of selenium and 200 mg/day of coenzyme Q10, combined. Blood samples were collected at inclusion and after 48 months for measurements of the intercellular adhesion molecule (ICAM-1), adiponectin, leptin, stem cell factor (SCF) and osteoprotegerin (OPG), using ELISAs. Repeated measures of variance and ANCOVA evaluations were used to compare the two groups. In order to better understand and reduce the complexity of the relationship between the biomarkers and age, factor analyses and structural equation modelling (SEM) were performed, and a structural model is presented. Correlation analyses of biomarker values at inclusion in relation to age, and relevant markers related to inflammation, endothelial dysfunction and fibrosis, demonstrated the biomarkers' association with these pathological processes; however, only ICAM1 and adiponectin were directly correlated with age. SEM analyses showed, however, that the biomarkers ICAM-1, adiponectin, SCF and OPG, but not leptin, all had significant associations with age and formed two independent structural factors, both significantly related to age. While no difference was observed at inclusion, the biomarkers were differently changed in the active treatment and placebo groups (decreasing and increasing levels, respectively) at 48 months ( ≤ 0.02 in all, adjusted), and in the SEM model, they showed an anti-ageing impact. Supplementation with selenium/Q10 influenced the analysed biomarkers in ways indicating an anti-ageing effect, and by applying SEM methodology, the interrelationships between two independent structural factors and age were validated.
Topics: Aged; Female; Humans; Male; Adiponectin; Aging; Biomarkers; Cardiovascular Diseases; Dietary Supplements; Intercellular Adhesion Molecule-1; Prospective Studies; Selenium; Sweden; Ubiquinone
PubMed: 37443807
DOI: 10.3390/cells12131773 -
BMC Musculoskeletal Disorders Feb 2021In dermatomyostis (DM) patients, inflammation, reduced activity, and medication have a negative impact on the musculoskeletal system. Several endocrine factors are...
BACKGROUND
In dermatomyostis (DM) patients, inflammation, reduced activity, and medication have a negative impact on the musculoskeletal system. Several endocrine factors are involved in muscle growth and bone turnover.
OBJECTIVE
We aimed to investigate factors regulating myogenesis and bone metabolism and to evaluate possible associations between these endocrine factors, muscle strength, and functional tests in DM patients.
METHODS
We conducted a cross-sectional study in 20 dermatomyositis patients. Serum levels of myostatin (MSTN), follistatin (FSTN), dickkopf 1 (Dkk1), sclerostin (SOST), periostin (PSTN), the receptor activator nuclear factor kB ligand (RANKL):osteoprotegerin (OPG) ratio and fibroblast growth factor 23 (FGF23) were determined. Physical function was evaluated by hand-held strength measurement, chair rising test, timed up and go test and the 3-min walking test.
RESULTS
Serum MSTN and FGF23 levels (2.5 [1.9; 3.2] vs. 1.9 [1.6; 2.3] and 2.17 [1.45; 3.26] vs. 1.28 [0.79; 1.96], respectively; p < 0.05) were significantly higher in DM patients than in controls. Dkk1 was significantly lower (11.4 [6.9; 20.0] vs. 31.8 [14.3; 50.6], p < 0.01). Muscle strength and physical function tests correlated with each other (e.g. hip flexion - timed up and go test: r = - 0.748, p < 0.01).
CONCLUSION
In DM patients, biochemical musculo-skeletal markers are altered and physical function shows deficits. All these tests reflect independent of each other different deficits in long-term DM patients which is important for the assessment of DM patients as well as planning of therapeutic interventions in clinical routine.
Topics: Biomarkers; Bone Morphogenetic Proteins; Cross-Sectional Studies; Dermatomyositis; Fibroblast Growth Factor-23; Humans; Myostatin; Osteoprotegerin; Postural Balance; RANK Ligand; Time and Motion Studies
PubMed: 33546660
DOI: 10.1186/s12891-021-04030-0 -
Cancer Genomics & Proteomics 2017Autoantibodies have potential as circulating biomarkers for early cancer detection. This study aimed to screen for known autoantibodies in human plasma using an... (Review)
Review
BACKGROUND/AIM
Autoantibodies have potential as circulating biomarkers for early cancer detection. This study aimed to screen for known autoantibodies in human plasma using an Autoantibody Profiling System (APS) and quantify the levels in plasma of donors with/without breast cancer.
MATERIALS AND METHODS
Plasma from nine female donors diagnosed with breast cancer (test group) and nine matched donors with no personal history of cancer (reference group) were screened with an APS containing probes for 30 autoantibodies. Autoantibody levels ≥1.5 times the mean concentration of the group were considered elevated, and test/reference ratios ≥1.3 were considered higher in the test group compared to the reference group.
RESULTS
Twenty percent of the probes detected elevated levels of autoantibodies against proteins involved in different cancer mechanisms. Amongst these, the levels of autoantibodies against interleukin 29 (IL29), osteoprotegerin (OPG), survivin (SUR), growth hormone (GRH) and resistin (RES) were significantly higher in the cancer group compared to the reference group (p<0.05), whereas the level of autoantibody against cytotoxic T-lymphocyte associated antigen-4 (CTLA4) was not significantly different between the two groups (p=0.38).
CONCLUSION
Disease-relevant autoantibodies were detected in the plasma of patients with breast cancer and donors without breast cancer. This means that identifying the type and level of autoantibodies in samples will be important in determining their significance in the disease process. A microtiter plate-based array system could be a fast and inexpensive screening method for identifying and quantifying autoantibodies in human plasma.
Topics: Adult; Autoantibodies; Breast Neoplasms; Female; Humans; Mass Screening; Young Adult
PubMed: 29109092
DOI: 10.21873/cgp.20052 -
PLoS Medicine Jan 2021Circulating biomarkers are associated with the development of coronary heart disease (CHD) and its complications by reflecting pathophysiological pathways and/or organ...
BACKGROUND
Circulating biomarkers are associated with the development of coronary heart disease (CHD) and its complications by reflecting pathophysiological pathways and/or organ dysfunction. We explored the associations between 157 cardiovascular (CV) and inflammatory biomarkers and CV death using proximity extension assays (PEA) in patients with chronic CHD.
METHODS AND FINDINGS
The derivation cohort consisted of 605 cases with CV death and 2,788 randomly selected non-cases during 3-5 years follow-up included in the STabilization of Atherosclerotic plaque By Initiation of darapLadIb TherapY (STABILITY) trial between 2008 and 2010. The replication cohort consisted of 245 cases and 1,042 non-cases during 12 years follow-up included in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study between 1997 and 2000. Biomarker levels were measured with conventional immunoassays and/or with the OLINK PEA panels CVD I and Inflammation. Associations with CV death were evaluated by Random Survival Forest (RF) and Cox regression analyses. Both cohorts had the same median age (65 years) and 20% smokers, while there were slight differences in male sex (82% and 76%), hypertension (70% and 78%), and diabetes (39% and 30%) in the respective STABILITY and LURIC cohorts. The analyses identified 18 biomarkers with confirmed independent association with CV death by Boruta analyses and statistical significance (all p < 0.0001) by Cox regression when adjusted for clinical characteristics in both cohorts. Most prognostic information was carried by N-terminal prohormone of brain natriuretic peptide (NTproBNP), hazard ratio (HR for 1 standard deviation [SD] increase of the log scale of the distribution of the biomarker in the replication cohort) 2.079 (95% confidence interval [CI] 1.799-2.402), and high-sensitivity troponin T (cTnT-hs) HR 1.715 (95% CI 1.491-1.973). The other proteins with independent associations were growth differentiation factor 15 (GDF-15) HR 1.728 (95% CI 1.527-1.955), transmembrane immunoglobulin and mucin domain protein (TIM-1) HR 1.555 (95% CI 1.362-1.775), renin HR 1.501 (95% CI 1.305-1.727), osteoprotegerin (OPG) HR 1.488 (95% CI 1.297-1.708), soluble suppression of tumorigenesis 2 protein (sST2) HR 1.478 (95% CI 1.307-1.672), cystatin-C (Cys-C) HR 1.370 (95% CI 1.243-1.510), tumor necrosis factor-related apoptosis-inducing ligand receptor 2 (TRAIL-R2) HR 1.205 (95% CI 1.131-1.285), carbohydrate antigen 125 (CA-125) HR 1.347 (95% CI 1.226-1.479), brain natriuretic peptide (BNP) HR 1.399 (95% CI 1.255-1.561), interleukin 6 (IL-6) HR 1.478 (95% CI 1.316-1.659), hepatocyte growth factor (HGF) HR 1.259 (95% CI 1.134-1.396), spondin-1 HR 1.295 (95% CI 1.156-1.450), fibroblast growth factor 23 (FGF-23) HR 1.349 (95% CI 1.237-1.472), chitinase-3 like protein 1 (CHI3L1) HR 1.284 (95% CI 1.129-1.461), tumor necrosis factor receptor 1 (TNF-R1) HR 1.486 (95% CI 1.307-1.689), and adrenomedullin (AM) HR 1.750 (95% CI 1.490-2.056). The study is limited by the differences in design, size, and length of follow-up of the 2 studies and the lack of results from coronary angiograms and follow-up of nonfatal events.
CONCLUSIONS
Profiles of levels of multiple plasma proteins might be useful for the identification of different pathophysiological pathways associated with an increased risk of CV death in patients with chronic CHD.
TRIAL REGISTRATION
ClinicalTrials.gov NCT00799903.
Topics: Aged; Biomarkers; Blood Proteins; Coronary Disease; Female; Fibroblast Growth Factor-23; Humans; Male; Prognosis; Retrospective Studies; Risk Factors
PubMed: 33439866
DOI: 10.1371/journal.pmed.1003513 -
Revista Espanola de Cirugia Ortopedica... 2022The scope of this study was to assess salivary and serum osteoprotegerin (OPG) levels in knee osteoarthritis (OA).
OBJECTIVE
The scope of this study was to assess salivary and serum osteoprotegerin (OPG) levels in knee osteoarthritis (OA).
METHODS
Serum and saliva OPG levels of 30 knee OA and 30 matched healthy controls in this cross-sectional study was assessed by ELISA. Knee pain was assessed by WOMAC. Data were analyzed by Student's t-test, Spearman correlation test and ROC.
RESULTS
The mean serum but not saliva OPG level was lower in knee OA than that of the healthy group. WOMAC negatively correlated with serum OPG (r = -0.501; P = 0.000). The serum OPG cutoff value was 237.5 pg/ml for the diagnosis of knee OA.
CONCLUSIONS
As serum OPG was lower in knee OA and negatively correlated with WOMAC, it seems that detection of OPG in serum but not in saliva may be a probable marker to the diagnosis of knee OA.
KEY MESSAGES
Osteoprotegerin decreases in knee osteoarthritis.
PubMed: 34147417
DOI: 10.1016/j.recot.2021.02.003 -
Frontiers in Aging Neuroscience 2021: Parkinson's disease (PD) and osteoporosis are both common aging diseases. It is reported that PD has a close relationship with osteoporosis and bone secretory proteins...
: Parkinson's disease (PD) and osteoporosis are both common aging diseases. It is reported that PD has a close relationship with osteoporosis and bone secretory proteins may be involved in disease progression. : To detect the bone-derived factors in plasma and cerebrospinal fluid (CSF) of patients with PD and evaluate their correlations with C-reaction protein (CRP) level, motor impairment, and Hoehn-Yahr (HY) stage of the disease. : We included 250 PD patients and 250 controls. Levels of osteocalcin (OCN), osteopontin (OPN), osteoprotegerin (OPG), Sclerostin (SO), Bone morphogenetic protein 2 (BMP2), and Dickkopf-1 (DKK-1) in plasma and CSF were measured by custom protein antibody arrays. Data were analyzed using Mann-Whitney -test and Spearman's receptor activator of NF-κB (RANK) correlation. : Plasma levels of OCN and OPN were correlated with CRP levels and HY stage and motor impairment of PD. Furthermore, the plasma assessment with CSF detection may enhance their potential prediction on PD. : OCN and OPN may serve as potential biomarkers for PD. The inflammation response may be involved in the cross-talk between the two factors and PD.
PubMed: 33732138
DOI: 10.3389/fnagi.2021.634213 -
Frontiers in Endocrinology 2022Glucocorticoids (GCs) induce osteoporosis, which results in fractures in the bond, causing significant morbidity. In the conducted study, we examined the...
BACKGROUND
Glucocorticoids (GCs) induce osteoporosis, which results in fractures in the bond, causing significant morbidity. In the conducted study, we examined the antiosteoporosis effect of dieckol against GC-induced osteoporosis in rats.
METHODS
Sprague-Dawley (SD) rats were used for the current study and dexamethasone (2.5 mg/kg) induced osteoporosis in the rats that received the dieckol (test) and alendronate (standard) for 20 weeks. Bone turnover parameters, microCT, antioxidant, inflammatory cytokines, nutrient, and hormones parameters.
RESULTS
Dieckol noticeably suppressed the body weight and boosted the uterine and vagina weight. Dieckol considerably altered the level of trabecular number (Tb. N), the bone volume to total volume (BV/TV), trabecular separation (Tb.Sp), bone surface to bone volume (BS/BV), and trabecular thickness (Tb.Th). Dieckol noticeably (P < 0.001) elevated the level of osteocalcin (OC) and alleviated the level of bone Gla protein (BGP), acid phosphatase (ACP), alkaline phosphatase (ALP), and β-CTx. Dieckol markedly boosted the level of malondialdehyde (MDA) and suppressed the level of glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) along with the suppression of inflammatory cytokines like TNF-α, IL-1β, and IL-6. Dieckol remarkably increased the level of calcium, potassium, magnesium, and 25 (OH) vitamin D. Dieckol substantially (P < 0.001) boosted the level of estradiol and alleviated the level of parathyroid hormone and tartrate-resistant acid phosphatase (TRAP). Dieckol also suppressed the level of receptor activator of nuclear factor κB ligand (RANKL) and boosted the level of osteoprotegerin (OPG).
CONCLUSION
Taken together, our data suggest that dieckol demonstrated the anti-osteoporosis effect against GC-induced osteoporosis in rats.
Topics: Animals; Benzofurans; Cytokines; Female; Glucocorticoids; Osteocalcin; Osteoporosis; Rats; Rats, Sprague-Dawley
PubMed: 36060953
DOI: 10.3389/fendo.2022.932488