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Advances in Clinical and Experimental... Feb 2023Current evidence suggests that nevoid basal cell carcinoma syndrome (NBCCS)-associated odontogenic keratocysts (OKCs) exhibit more aggressive clinical behavior and a...
BACKGROUND
Current evidence suggests that nevoid basal cell carcinoma syndrome (NBCCS)-associated odontogenic keratocysts (OKCs) exhibit more aggressive clinical behavior and a higher tendency to relapse. The prognostic efficacy of various markers in sporadic and syndromic OKCs is unclear, and so are the results of studies on the usefulness of immunohistochemistry in distinguishing syndromic from sporadic OKCs.
OBJECTIVES
This retrospective study aimed to compare the prognostic relevance of various clinicoradiological and histopathological features, as well as the immunoexpression of COX-2, Bcl-2, proliferating cell nuclear antigen (PCNA), p53, Ki-67, osteoprotegerin (OPG), receptor activator of nuclear factor κ B (RANK) and receptor activator of nuclear factor κ B ligand (RANKL), as well as RANKL/OPG balance between sporadic and syndromic OKCs, and to test their utility in distinguishing the 2 types of OKC.
MATERIAL AND METHODS
We compared the immunoexpression of the aforementioned markers between 31 sporadic and 12 syndromic OKCs, and tested clinicopathological findings and levels of immunostaining against recurrence.
RESULTS
We found a significant association between NBCCS and OKC recurrence. There were significant differences in PCNA, p53 and OPG immunoexpression between sporadic and syndromic OKCs. We also found that recurrent sporadic OKCs were significantly larger and markedly more often associated with cortical perforation. Recurrent sporadic OKCs exhibited COX-2 upregulation, but we failed to demonstrate its prognostic relevance. Recurrent syndromic OKCs showed a markedly higher RANKL > OPG ratio.
CONCLUSIONS
The NBCCS-associated OKCs are significantly more prone to recur than their sporadic counterparts. Larger size and radiological signs of cortical perforation in sporadic OKCs may indicate a higher risk of recurrence. The COX-2 is upregulated in recurrent sporadic OKCs, whereas recurrent syndromic OKCs exhibit higher RANKL and lower OPG expression; however, these findings have no prognostic relevance. The immunoexpression of p53, PCNA and OPG may help to distinguish syndromic from sporadic OKCs.
Topics: Humans; Basal Cell Nevus Syndrome; Proliferating Cell Nuclear Antigen; Retrospective Studies; Cyclooxygenase 2; Tumor Suppressor Protein p53; Neoplasm Recurrence, Local; Odontogenic Cysts; Odontogenic Tumors
PubMed: 36226690
DOI: 10.17219/acem/153390 -
Journal of Orthopaedic Translation Nov 2022Osteogenesis and angiogenesis are important for bone fracture healing. Irisin is a muscle-derived monokine that is associated with bone formation.
BACKGROUND
Osteogenesis and angiogenesis are important for bone fracture healing. Irisin is a muscle-derived monokine that is associated with bone formation.
METHODS
To demonstrate the effect of irisin on bone fracture healing, closed mid-diaphyseal femur fractures were produced in 8-week-old C57BL/6 mice. Irisin was administrated intraperitoneally every other day after surgery, fracture healing was assessed by using X-rays. Bone morphometry of the fracture callus were assessed by using micro-computed tomography. Femurs of mice from each group were assessed by the three-point bending testing. Effect of irisin on osteogenic differentiation in mesenchymal stem cells was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR), alkaline phosphatase staining and alizarin red staining. Angiogenesis of human umbilical vein endothelial cells (HUVECs) were evaluated by qRT-PCR, migration tests, and tube formation assays.
RESULTS
Increased callus formation, mineralization and tougher fracture healing were observed in the irisin-treated group than in the control group, indicating the better fracture callus healing due to Irisin treatment. The vessel surface and vessel volume fraction of the callus also increased in the irisin-treated group. The expression of BMP2, CD31, and VEGF in callus were enhanced in the irisin-treated group. In mouse bone mesenchymal stem cells, irisin promoted ALP expression and mineralization, and increased the expression of osteogenic genes, including , , , , and . Irisin also promoted HUVEC migration and tube formation. Expression of angiogenic genes, including , , , , , and in HUVECs were increased by irisin.
CONCLUSION
All the results indicate irisin can promote fracture healing through osteogenesis and angiogenesis. These findings help in the understanding of muscle-bone interactions during fracture healing.
THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE
Irisin was one of the most important monokine secreted by skeletal muscle. Studies have found that irisin have anabolic effect one bone remodeling through affecting osteocyte and osteoblast. Based on our study, irisin could promote bone fracture healing by increasing bone mass and vascularization, which provide a potential usage of irisin to promote fracture healing and improve clinical outcomes.
PubMed: 36196152
DOI: 10.1016/j.jot.2022.07.006 -
BMC Endocrine Disorders Sep 2022Decreased baroreflex sensitivity (BRS) has been shown to be a marker of cardiovascular (CV) risk. In the present study, the difference in CV risk biomarkers in type 2...
Hypertension attenuates the link of osteoprotegerin to reduced baroreflex sensitivity in type 2 diabetes mellitus patients on oral antidiabetic and antihypertensive therapy - a cross sectional study.
PURPOSE
Decreased baroreflex sensitivity (BRS) has been shown to be a marker of cardiovascular (CV) risk. In the present study, the difference in CV risk biomarkers in type 2 diabetes (T2D) patients receiving oral antidiabetic drugs (OAD) with and without hypertension has been assessed.
MATERIALS AND METHODS
Ninety-two T2D patients on OAD without hypertension (control group) and eighty-eight diabetic patients with hypertension on OAD and antihypertensive drugs (test group) matched for age, gender, body mass index, serum glucose, glycated haemoglobin, and duration of the disease were recruited for the study. Their blood pressure (BP) variability including BRS, heart rate variability (HRV), insulin, lipid profile, osteoprotegerin (OPG), and tumor necrosis factor-α (TNF-α) were estimated. The association of various factors with BRS was assessed by Spearman correlation and multiple regression analysis.
RESULTS
BRS was decreased (13.90 ± 5.27 vs 6.76 ± 4.58), HRV sympathetic indices [LFnu, LF-HF ratio (1.30 ± 0.49 vs 1.93 ± 0.62)], HOMA-IR, atherogenic index of plasma (AIP), OPG (223.08 ± 103.86 vs 287.60 ± 121.36) and TNF-α were increased, and parasympathetic indices [TP (1012.90 ± 316.18 vs 625.88 ± 229.84), RMSSD, SDNN, NN50, pNN50] were decreased in the test group compared to control group. In control group, parasympathetic indices, AIP, OPG, and TNF-α had a significant correlation and OPG had an independent association (β - 0.344; p 0.004) with BRS. In test group, BP, LF-HF ratio, parasympathetic indices, AIP, OPG, and TNF-α had significant correlation, and TNF-α alone (β - 0.297; p 0.022) had an independent contribution to decreased BRS.
CONCLUSION
Despite antidiabetic and antihypertensive treatments, T2D patients with hypertension had more cardiometabolic risks in comparison to normotensive T2D patients. Inflammation could be the inciting factor for rise in BP and decrease in BRS (CV risk) in hypertensive T2D patients. Hypertension in diabetes could attenuate the link of OPG to the reduction in BRS. Reduction in BRS could be a physiological marker of CV risk in T2D patients treated with OAD.
Topics: Antihypertensive Agents; Baroreflex; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Humans; Hypertension; Hypoglycemic Agents; Osteoprotegerin; Tumor Necrosis Factor-alpha
PubMed: 36085061
DOI: 10.1186/s12902-022-01137-w -
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 -
Frontiers in Endocrinology 2022Childhood obesity contributes to the development of cardiovascular diseases. The molecular pathway - receptor activator of nuclear factor-κβ ligand (RANKL), its...
INTRODUCTION
Childhood obesity contributes to the development of cardiovascular diseases. The molecular pathway - receptor activator of nuclear factor-κβ ligand (RANKL), its receptor RANK and osteoprotegerin (OPG) - takes part not only in bone metabolism but is also involved in the atherosclerosis process. RANKL stimulates osteogenic differentiation and calcification of vascular smooth cells. The associations between the OPG-sRANKL system and various cardiovascular risk factors were displayed. We aimed to evaluate the relationships between serum sRANKL (soluble RANKL) levels and the OPG/sRANKL ratio with cardiometabolic risk factors in overweight and obese children.
MATERIAL AND METHODS
The study included 70 children with overweight and obesity (mean age 13.0 ± 2.8) and 35 age-matched normal weight, healthy peers as a control group. In all patients, anthropometric measurements and laboratory tests were performed. Additionally, an oral glucose tolerance test (OGTT) was made only in overweight and obese children. Atherogenic and insulin resistance indices were calculated.
RESULTS
Overweight and obese children had lower sRANKL levels compared to the control group (median 276.95 vs 325.90, p=0.011), and consequently a higher OPG/sRANKL ratio (0.02 vs 0.01, p = 0.013). The studied children in the lowest quartile of sRANKL levels had higher body weight, Body Mass Index, waist circumference and increased glucose and insulin levels 60 minutes after OGTT and higher uric acid values compared to children in the highest quartile. In multivariable linear regression analysis sRANKL negatively correlated only with uric acid (β = - 0.508, p = 0.041). No association was found for the OPG/sRANKL ratio.
CONCLUSION
Excess fat mass seems to alter the OPG/RANKL ratio mainly by reducing serum sRANKL levels. The correlation between sRANKL and uric acid may suggest a contribution of the OPG-sRANKL system in the cardiometabolic process, but that observation should be confirmed in future studies.
Topics: Adolescent; Child; Humans; Ligands; Osteogenesis; Osteoprotegerin; Overweight; Pediatric Obesity; RANK Ligand; Uric Acid
PubMed: 36060948
DOI: 10.3389/fendo.2022.963467 -
Diabetes Care Sep 2022To use protein biomarkers to identify people with type 2 diabetes at high risk of cardiovascular outcomes and death. (Clinical Trial)
Clinical Trial
OBJECTIVE
To use protein biomarkers to identify people with type 2 diabetes at high risk of cardiovascular outcomes and death.
RESEARCH DESIGN AND METHODS
Biobanked serum from 4,957 ELIXA (Evaluation of Lixisenatide in Acute Coronary Syndrome) trial participants was analyzed. Forward-selection Cox models identified independent protein risk factors for major adverse cardiovascular events (MACE) and death that were compared with a previously validated biomarker panel.
RESULTS
NT-proBNP and osteoprotegerin predicted both outcomes. In addition, trefoil factor 3 predicted MACE, and angiopoietin-2 predicted death (C = 0.70 and 0.79, respectively, compared with 0.63 and 0.66 for clinical variables alone). These proteins had all previously been identified and validated. Notably, C statistics for just NT-proBNP plus clinical risk factors were 0.69 and 0.78 for MACE and death, respectively.
CONCLUSIONS
NT-proBNP and other proteins independently predict cardiovascular outcomes in people with type 2 diabetes following acute coronary syndrome. Adding other biomarkers only marginally increased NT-proBNP's prognostic value.
Topics: Acute Coronary Syndrome; Biomarkers; Diabetes Mellitus, Type 2; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Risk Assessment; Risk Factors
PubMed: 35817031
DOI: 10.2337/dc22-0453 -
Experimental and Therapeutic Medicine Aug 2022The present study explored the potential role of osteoprotegerin (OPG)/receptor activator of nuclear factor-κB (RANK)/receptor activator of nuclear factor-κB ligand...
The present study explored the potential role of osteoprotegerin (OPG)/receptor activator of nuclear factor-κB (RANK)/receptor activator of nuclear factor-κB ligand (RANKL) in promoting vascular calcification by periodontitis. Thirty-six male Wistar rats were randomly assigned to four groups to establish animal models as follows: the sham group (group C), vascular calcification group (group VDN), periodontitis group (group CP), and test group (group CP+VDN). After eight weeks, all the rats were sacrificed. The periodontal and vascular calcification indices were detected. Quantitative polymerase chain reaction (qPCR), immunohistochemistry, western blot analysis, and enzyme-linked immunosorbent assay (ELISA) were used to quantify OPG/RANK/RANKL expression in vascular tissue and serum. Protein expression analyses revealed the expression of OPG and RANKL in the vascular tissues of the four groups. The expression of OPG in group C was the highest, which was similar to group CP+VDN, and the expression of OPG in groups CP and VDN were lower. However, the expression of RANKL was inversely correlated with OPG, and the ratio of RANKL/OPG was also higher in groups CP and VDN than that in groups C and CP+VDN. In conclusion, OPG/RANK/RANKL may play an essential role in the promotion of vascular calcification by periodontitis. However, the expression levels of OPG and RANKL were not simply superimposed when periodontitis and vascular calcification co-existed.
PubMed: 35813311
DOI: 10.3892/etm.2022.11439 -
Computational Intelligence and... 2022The target of the present paper was to reveal the influence of LncRNA BC083743 on osteogenesis in human bone marrow mesenchymal stem cells (hBMSCs).
OBJECTIVE
The target of the present paper was to reveal the influence of LncRNA BC083743 on osteogenesis in human bone marrow mesenchymal stem cells (hBMSCs).
METHODS
Serum specimens from osteoporotic patients and normal subjects were collected to isolate hBMSCs from femoral head tissue. The levels of BC083743 and miR-103-3p in serum and hBMSCs were measured by QRT-PCR. Alkaline phosphatase (ALP) activity test and alizarin red dyeing were used to identify ALP activity and mineralization forming ability of hBMSCs after transfection with si-BC083743 (siRNA-targeting BC083743). In addition, QRT-PCR and immunoblotting were conducted to identify the expressing levels of Runt-related transcription factor 2(Runx2), osteoprotegerin (OPG), and bone morphogenetic protein 2 (BMP2) in hBMSCs. Dual-luciferase reporter gene and RNA pull-down assays were employed to substantiate the binding of BC083743 to miR-103-3p and miR-103-3p to SATB2.
RESULTS
BC083743 expression was significantly downregulated in sera from patients with osteoporosis, and osteogenic differentiation-related genes and BC083743 expression were obviously upregulated as the time to osteogenic differentiation increased. BC083743 knockdown hindered the osteogenic differentiation of hBMSCs. BC083743 was aimed at miR-103-3p and miR-103-3p inhibitors partially reversed the inhibitory effect of BC083743 downregulation on hBMSCs osteogenesis. BC083743 silencing downregulated SATB2 through uptake of miR-103-3p, thereby inhibiting hBMSCs osteogenesis to exacerbate osteoporosis.
CONCLUSION
BC083743/miR-103-3p/SATB2 axis inhibited osteogenic differentiation and exacerbated osteoporosis, which may offer brand-new molecular aims for the treatment of clinical osteoporosis.
Topics: Cells, Cultured; Humans; Matrix Attachment Region Binding Proteins; MicroRNAs; Osteogenesis; Osteoporosis; RNA, Long Noncoding; Transcription Factors
PubMed: 35769281
DOI: 10.1155/2022/7066759 -
Journal of Clinical Medicine Jun 2022Hyperandrogenism is the most common endocrine disorder in women, characterized by an imbalance of normal estrogen and androgen levels in the blood. Androgens play an...
Hyperandrogenism is the most common endocrine disorder in women, characterized by an imbalance of normal estrogen and androgen levels in the blood. Androgens play an important role in the female body because they influence bone mineral density (BMD), body mass composition, muscle mass, mental state, and the regulation of sexual function. The reduced activity of aromatase, due to mutations in the gene, reduces the estrogen pool in favor of androgens. Clinically, aromatase deficiency causes hyperandrogenism in women. Therefore, the aim of the study was to assess the effect of the gene polymorphism on selected markers of bone metabolism and hormonal parameters in women with hyperandrogenism. The study group was comprised of 80 young women with hyperandrogenism who underwent measurements of bone mineral density (BMD), and determination of hormonal and metabolic parameters. Enzyme immunoassays were used to measure leptin, total sRANKL (free and bound RANKL), osteoprotegerin, and total 25-OH Vitamin D. An analysis of the gene polymorphisms was performed using the real-time PCR method. The GG genotype of the rs700518 polymorphism turned out to be associated with: FEI (Free Estradiol Index), SHGB concentration, estradiol concentration, and insulin concentration determined in the glucose tolerance test 60' compared to AG and AA genotypes. Patients with the AG genotype had a higher ratio of android to gynoid fat and a greater content of visceral adipose tissue. Higher visceral tissue content may reduce BMD. In conclusion, the study showed that the rs700518 polymorphism may be associated with the distribution of adipose tissue in young women with hyperandrogenism. These results suggest that patients with the AG genotype may develop osteoporosis.
PubMed: 35743606
DOI: 10.3390/jcm11123537 -
Frontiers in Nutrition 2022Dairy products and impact exercise have previously been identified to be independently beneficial for bone mineral properties, however, it is unknown how the combination...
Dairy products and impact exercise have previously been identified to be independently beneficial for bone mineral properties, however, it is unknown how the combination of these two osteogenic interventions may alter acute bone turnover. Using a randomized crossover design, we compared the acute effects of consuming milk vs. an isoenergetic carbohydrate control beverage on bone biomarkers following loading exercise. Thirteen healthy female participants (Age = 20.3 ± 2.3y; BMI = 21.0 ± 1.1 kg/m) consumed either 550 mL of 0% skim white milk (MILK) or 52.7 g of maltodextrin in 550 mL of water (CHO), both 5 min and 1 h following completion of a combined plyometric (198 impacts) and resistance exercise (3-4 sets/exercise, 8-12 reps/set, ∼75% 1-RM) bout. Venous blood samples were obtained pre-exercise, and 15 min, 75 min, 24 h and 48 h post-exercise to assess serum concentrations of bone resorption biomarkers, specifically carboxyl-terminal crosslinking telopeptide of type I collagen (CTX), receptor activator nuclear factor kappa-β ligand (RANKL), and sclerostin (SOST), as well as bone formation biomarkers, specifically osteoprotegerin (OPG) and osteocalcin (OC). When absolute biomarker concentrations were examined, there were no interaction or group effects for any biomarker, however, there were main time effects ( < 0.05) for RANKL, SOST, and OC, which were lower, and the OPG: OPG/RANKL ratio, which was higher at 75 min post-exercise compared with baseline in both conditions. In addition to assessing absolute biomarker concentrations at specific timepoints, we also evaluated the relative (% change) cumulative post-exercise response (75 min to 48 h) using an area under the curve (AUC) analysis. This analysis showed that the relative post-exercise CTX response was significantly lower in the MILK compared to the CHO condition ( = 0.03), with no differences observed in the other biomarkers. These results show that while milk does not appear to alter absolute concentrations of bone biomarkers compared to CHO, it may attenuate relative post-exercise bone resorption (i.e., blunt the usual catabolic response to exercise).
PubMed: 35571916
DOI: 10.3389/fnut.2022.840973