Osteocalcin Concentrations Research Articles

Sustainable Bioactive Composite of Glehnia littoralis Extracts for Osteoblast Differentiation and Bone Formation

Different bone-related diseases are mostly caused by the disruption of bone formation and bone resorption, including osteoporosis. Traditional medicinal literature has reported the possible anti-osteoporotic properties of Glehnia littoralis. However, the chemical compounds in extracts that are responsible for bone metabolism are poorly understood. The present study aimed to explore and compare the coumarin-based compounds present in G. littoralis extracts, the antioxidant activities, and the anti-osteoporotic properties of different extracts of G. littoralis (leaf and stem, fruit, whole plant, and root extracts) on bone metabolism. This study analyzed G. littoralis extract effects on the proliferation and osteoblastic differentiation of MC3T3-E1 osteoblasts. Among the different tested samples, stem extracts had the highest scopoletin (53.0 mg/g), and umbelliferone (1.60 mg/g). The significantly (p < 0.05) highest amounts of imperatorin (31.9 mg/g) and phellopterin (2.3 mg/g), were observed in fruit and whole plant extracts, respectively. Furthermore, the results confirmed alkaline phosphatase activity, collagen synthesis, mineralization, osteocalcin content, and osterix and RUNX2 expression. G. littoralis extracts at concentrations greater than 20 µg/mL had particularly adverse effects on MC3T3-E1 cell viability and proliferation. Notably, cell proliferation was significantly elevated at lower G. littoralis concentrations. Comparatively, 0.5 µg/mL stem had a higher osteocalcin content. Of the four extract types, stem showed a higher collagen synthesis effect at concentrations of 0.5–5 µg/mL. Except for fruit extracts, G. littoralis extract treatment significantly elevated osterix gene expression. All G. littoralis extracts increased RUNX2 gene expression. The results described here indicate that G. littoralis ethanolic extracts can effectively prevent osteoporosis.

Serum Osteocalcin, Sclerostin and Lipocalin-2 Levels in Adolescent Boys with Obesity over a 12-Week Sprint Interval Training.

The aim of the study was to examine the effects of supervised cycling sprint interval training (SIT) on serum osteocalcin, lipocalin-2 and sclerostin levels, and bone mineral characteristics among obese adolescent boys. Untrained obese adolescent boys aged 13.4 ± 0.3 were assigned to either a 12-week SIT group (3 sessions/week), or a non-exercising control group who continued with their habitual everyday life. Serum osteocalcin, lipocalin-2 and sclerostin concentrations, and bone mineral values were assessed before and after intervention. After 12-week intervention, where 14 boys in both groups ended the study, there were no significant differences in serum osteokine levels between the groups after 12 weeks, while whole body bone mineral content and lower limb bone mineral density increased in the SIT group (p < 0.05). Change in body mass index was negatively correlated with the change in osteocalcin (r = -0.57; p = 0.034), and positively correlated with the change in lipocalin-2 levels (r = 0.57; p = 0.035) in the SIT group. Supervised 12-week SIT intervention improved bone mineral characteristics, but did not change osteocalcin, lipocalin-2 or sclerostin levels in adolescent boys with obesity.

CORRELATION OF SERUM OSTEOCALCIN LEVEL WITH THE INDICES OF OBESITY AND LIPID PROFILE IN TYPE II DIABETIC SUDANESE PATIENTS

Objectives:Osteocalcin, an osteoblast-specific protein, has recently been reported to affect energy metabolism, this study aimed to assess the relationship between serum total osteocalcin and measurements of adiposity and lipid profile in type II diabetic Sudanese patients. Methods: In this cross-sectional study, 115 people with type II diabetes (34 men, 81 women) aged 18 to 94 years were enrolled in the study. Total osteocalcin and insulin were measured using ELISA (enzyme-linked immunosorbent assay) technique. Fasting blood glucose and lipid profile were measured by a spectrophotometer. Results: Mean serum osteocalcin concentration in diabetic patients was significantly lower than those in control subjects (p ≤ 0.001). When the test was done between TOC and lipid profile, there was a moderate negative correlation between TOC and TCHOL. Which was statistically significant (P = 0.003). There was a moderate negative correlation between TOC and TG. Which was statistically non-significant (P = 0.057). There was a strong positive correlation between TOC and HDL. Which was statistically significant (P = 0.000). There was a weak positive correlation between TOC and LDL. That is statistically non-significant P = 0.105. Conclusion:Our findings showed a statistically highly significant negative correlation between TOC and fasting blood glucose concentration. Similarly, the correlation between FBG and ucOC, age, BMI, TCHOL, and HDL showed a negative correlation that was not significant.

Association of osteocalcin, osteoprotegerin, and osteopontin with cardiovascular disease and retinopathy in type 2 diabetes.

Novel biomarkers of vascular disease in diabetes could help identify new mechanistic pathways. Osteocalcin, osteoprotegerin, and osteopontin are key molecules involved in bone and vascular calcification processes, both of which are compromised in diabetes. We aimed to evaluate possible associations of osteocalcin, osteoprotegerin, and osteopontin with cardiovascular disease (CVD) and diabetic retinopathy (DR) among people with type 2 diabetes (T2D). Osteocalcin, osteoprotegerin, and osteopontin concentrations were measured at enrolment in 848 participants with T2D from the Sapienza University Mortality and Morbidity Event Rate (SUMMER) Study (ClinicalTrials.gov: NCT02311244). Logistic regression models and propensity score matching were used to assess possible associations of osteocalcin, osteoprotegerin, and osteopontin with a history of CVD and with evidence of any grade of DR adjusting for confounders. Previous CVD was reported in 139 (16.4%) participants, while 144 (17.0%) had DR. After adjusting for possible confounders, osteocalcin but not osteoprotegerin or osteopontin concentrations were associated with a history of CVD (Odds Ratio [OR] and 95% CI for one standard deviation (SD) increase in osteocalcin concentrations (natural log): 1.35 (1.06-1.72), p=0.014). Associations with prevalent DR were seen for osteoprotegerin (OR for one SD increase in osteoprotegerin concentrations (natural log): 1.25 (1.01-1.55), p=0.047) and osteopontin (OR for one SD increase in osteopontin concentrations (natural log): 1.25 (1.02-1.53), p=0.022), but not osteocalcin. In T2D, higher serum osteocalcin concentrations are associated with macrovascular complications and higher osteoprotegerin and osteopontin concentrations with microvascular complications, suggesting that these osteokines might be involved in pathways directly related to vascular disease.

Age- and sex-specific differences in the association of serum osteocalcin and cardiometabolic risk factors in type 2 diabetes

BackgroundSerum osteocalcin levels are closely related to metabolic syndrome and cardiovascular disease. This study aimed to investigate the relationship between serum osteocalcin levels and cardiometabolic risk factors in patients with type 2 diabetes (T2D) according to age and sex.MethodsThis cross-sectional study included 1500 patients with T2D (991 men and 509 women) aged ≥ 18 years old. The age- and sex-specific disparities in glycemic and lipid control, as well as cardiometabolic risk factors were evaluated.ResultsThe levels of serum osteocalcin were significantly higher in women aged > 50 years compared with women aged ≤ 50 years (15.6 ± 6.5 ng/mL vs. 11.3 ± 4.5 ng/mL, p < 0.0001). However, this was lower in men aged > 50 years than men aged ≤ 50 years (12.2 ± 4.2 ng/mL vs. 12.9 ± 4.3 ng/mL, p = 0.0081). We performed correlation analyses of serum osteocalcin and cardiometabolic parameters. Serum osteocalcin concentrations were negative associated with FBG and HbA1c levels in women and men ≤ 50 years old, but not in men aged > 50 years old. Serum osteocalcin were negatively correlated with TG and positively correlated with HDL-C and LDL-C only in men aged ≤ 50 years. In binary logistic regression analysis, serum osteocalcin levels were associated with multiple cardiovascular risk factors, as follows: overweight/obese (odds ratio [OR], 0.944; 95% confidence interval [CI], 0.9–0.991, p = 0.02) in men aged > 50 years; high HbA1C and high FBG in women and men aged ≤ 50 years, but not in men aged > 50 years; after adjustment for confounding factors, high TG (OR, 0.905; 95% CI 0.865–0.947, p < 0.0001), metabolic syndrome (OR, 0.914; 95% CI 0.874–0.956, p < 0.0001), and low high-density lipoprotein cholesterol (OR, 0.933; 95% CI, 0.893–0.975, p = 0.002) were seen in men aged ≤ 50 years only.ConclusionsSerum osteocalcin level has significant relationships with cardiometabolic risk factors and several age- and sex-related differences in patients with T2D. Decreased serum osteocalcin levels are associated with a worse cardiometabolic risk profile.

Concurrent measurement of serum and radiomic biomarkers in the clinical investigation of equine musculoskeletal injuries: A prospective pilot study.

The prevention of musculoskeletal injuries and their relatedwelfare and economic impacts represent an immediate priority for the horse racing industry. This prospective pilot study aimed to evaluate a method to quantitatively analyze scintigraphic features of specific anatomical regions of the horse's appendicular skeleton in combination with secondary measures of musculoskeletal metabolism in blood. Twelve horses referred for scintigraphic assessment of lameness were enrolled. Blood samples were collected immediately prior to the administration of radiotracer. Serum concentrations associated with bone turnover were determined for the following biomarkers: C-terminal telopeptides of type I collagen, proteoglycans and sulfated glycosaminoglycans, collagen type II, osteocalcin, and procollagen II C-terminal propeptide. Scintigraphic images underwent radiomic analysis of discrete regions of the distal limbs and these data were correlated to bone turnover markers. Three lame horses demonstrated asymmetrical radiomic abnormalities. The concentration of osteocalcin in the lame horses was significantly higher when compared to the control group, while no significant changes were observed for the other screened serum biomarkers. Findings from the current study provided evidence that radiomic analysis of equine scintigraphy is feasible. This method has the potential to interrogate which serum markers are associated with musculoskeletal injuries.

Aging and Food Restriction Alter Some Indices of Bone Metabolism in Male Rhesus Monkeys (Macaca mulatta)

Food restriction increases life span, reduces aging rate and affects a wide variety of biological functions. In rats, food restriction delays bone growth and reduces bone density and mineral content. We report the effects of aging and long-term (>6.0 y) food restriction on several indices of bone growth and metabolism in rhesus monkeys (Macaca mulatta). Food allotments for controls approximated free access consumption, whereas food-restricted monkeys received 30% less food on a body weight basis. Cross-sectional and longitudinal age effects on serum alkaline phosphatase paralleled those reported for humans. Food restriction induced a significant delay in the developmental decline (to adult levels) in total alkaline phosphatase and significantly suppressed serum interleukin 6 concentrations, particularly in younger monkeys. Also, food restriction slowed skeletal growth, as reflected by shorter crown-rump length, and significantly reduced total body bone mineral content, but not bone mineral density, measured by dual energy X-ray absorptiometry. Analyses of serum parathyroid hormone, calcium, phosphate and osteocalcin concentrations suggested that the effects on skeletal growth were not related to alterations in calcium and phosphate homeostasis or a primary defect in bone formation. These findings suggest that long-term food restriction delays skeletal development in male rhesus monkeys while allowing the development of a reduced but otherwise normal skeleton.

Rat Serum Osteocalcin Concentration Is Decreased by Restriction of Energy Intake

We studied the effects of energy restriction on serum osteocalcin concentration and bone formation rate in rats. The experiment was designed to achieve energy restriction by reducing the carbohydrate intake while providing identical quantities of protein, fat, vitamins and minerals. Energy intakes of three groups of post-weaning male rats were restricted by 20, 40 and 60% for 4 wk. Serum calclum, phosphorus, transthyretin, triiodothyronine (T3), thyroxine (T4), 1,25-dihydroxycholecalciferol, 25-hydroxycholecalciferol and immunoreactive parathyroid hormone (iPTH) concentrations were determined. Energy restriction (20, 40 and 60%) produced a significant and gradual drop of serum osteocalcin concentrations, although the serum concentrations of its key regulators, i.e., 1,25-dihydroxycholecalciferol and iPTH, were not significantly affected. On the contrary, serum concentrations of calcium, phosphorus, transthyretin, T3 and T4 were significantly lower in the energy-restricted groups. However, our results do not support their implication in the regulation of serum osteocalcin synthesis by energy intake. Serum osteocalcin concentration was positively correlated with bone mineral apposition (r = 0.50, P < 0.05) and bone mineralization (r = 0.50, P < 0.05) rates suggesting that its decrease resulted from a reduction of bone formation, and not from abnormal mineralization, because osteoid seam thickness was not modified. Energy intake seems to be an important determinant of serum osteocalcin concentration and bone formation; however, the exact mechanism underlying this regulation remains to be determined.

The influence of sex and age on bone turnover markers in the adult to geriatric Kangal shepherd dogs.

The objective of this research was to learn more about bone metabolism in intact female and male Kangal shepherd dogs during the aging process following skeletal maturity. It also evaluated the potential application of biochemical bone indicators in veterinary clinical practice. Bone markers were determined as bone alkaline phosphatase (BALP), osteocalcin (OC), C-terminal telopeptide of type I collagen (CTX), and cross-linked C-telopeptide of type I collagen (ICTP) in this study. Kangal shepherd dogs of different age (adult, senior, and geriatric) and sex (male and female) groups were split into six groups of equal numbers (n=8/group). In this study, the effect of age was observed on serum BALP, OC, CTX, and ICTP concentrations. Specifically, BALP was highest in geriatric female Kangal shepherd dogs, while serum OC, CTX, and ICTP concentrations were highest in geriatric male Kangal shepherd dogs. However, no effects of sex and age-sex interactions were identified. Moreover, the effects of age, sex, and age-sex interactions had no significant effect on serum creatinine, CK, LDH, Mg, and P concentrations or ALT activities. However, only sex was found to affect serum AST activities and gradually decreased with age in females. The effect of age and age-sex interactions on serum Ca concentrations was significant (the lowest serum Ca concentrations were in geriatric females), but the effect of sex was not. These results show the effect of age and sex on bone turnover in Kangal shepherd dogs and provide information about bone biomarkers.

Efeito da caminhada com restrição do fluxo sanguíneo em idosas com osteoporose/osteopenia

Abstract Introduction The preservation of bone mass in elderly women is associated with better levels of practice of systematic physical exercises. Aerobic training combined with blood flow restriction seems to be a new alternative that determines this process, but knowledge gaps are still observed when referring to exercise associated with blood flow restriction (BFR) and adaptations on bone variables. Objective To analyze the chronic effects of aerobic training with and without BFR on bone mineral density and bone biomarker osteocalcin concentrations in older women. Methods Thirty women were randomized into the following groups: walking on a treadmill at low intensity with BFR; moderate treadmill walking with no BFR; only BFR (no exercise) for 20 minutes, twice a week, for 24 weeks. Bone mineral density was measured before and 24 weeks after intervention. Blood serum osteocalcin concentrations were measured before, 12 and 24 weeks after intervention. Results There were no differences between groups in bone mineral density (femoral neck, p = 0.31; total femur, p = 0.17; lumbar spin, p = 0.06) and osteocalcine (W(2) = 0.27; p = 0.87) ouctomes after 24 weeks of intervention. Conclusion There was no difference between walking training, blood flow restriction only, or walking+blood flow restriction on bone mineral density and osteocalcin concentrations after 24-weeks of intervention in older women with osteopenia/osteoporosis.

Proteins and Our Past: An Exploration of Human Bone Protein from the Eighteenth-Century Fortress of Louisbourg, Nova Scotia, and Its Potential Applications in Bioarchaeological Research

Bioarchaeologists can further investigate human bone metabolism at the biomolecular level by incorporating biochemical methods into their research. Recently, there has been a focus on osteocalcin, an abundant non-collagenous bone protein, because of its clinically identified relationship with biological factors (i.e., age and sex), activity, and pathological conditions (i.e., disease). For this study, osteocalcin was extracted and quantified from the femora of 27 individuals from the Fortress of Louisbourg (1713–1758) skeletal collection to explore if the clinical relationship between osteocalcin and sex, age, activity, and pathological conditions can also be established in archaeological bone. However, no significant relationships between osteocalcin concentrations and biological factors (i.e., age and sex), activity, or pathological conditions were identified. This is the first study to quantify osteocalcin from archaeological human skeletal remains from a Canadian context and provides another example of how this method may be used to study stress in bioarchaeological populations.

The role of bone turnover markers in screening low bone mineral density and their relationship with fracture risk in the postmenopausal period.

Using bone turnover marker (BTM) monitoring to identify "quick losers" who may develop osteoporosis in the coming years is one of the main challenges in clinical practice. This study was implemented to examine the association of BTMs with bone mineral density (BMD) as well as to determine their relationship with the fracture risk assessment tool (FRAX) in women in the postmenopausal period. This study was observational cross-sectional research that was done on women between the ages of 50 and 65 who were in the postmenopausal period. A dual-energy X-ray absorptiometry was applied to select 120 eligible women with normal BMD and 120 women without normal BMD. BTMs were assessed using enzyme-linked immunosorbent assay. Osteoporosis's Odds Ratio (OR) was estimated using a confounder-adjusted logistic regression model. The area under curve was calculated for the differentiation of low BMD in the postmenopausal period through receiver-operator characteristic (ROC) curves. To assess the probability of major osteoporotic fracture and hip fracture for the future 10 years, FRAX was applied. Higher serum osteocalcin (OC) (OR: 1.134, 95% confidence interval [CI]: 1.086-1.184), osteopontin (OP) (OR: 1.180; 95%CI: 1.105-1.261), and alkaline phosphatase (ALP) (OR: 1.007; 95%CI: 1.001-1.144) concentrations were potential risk factors for developing low BMD in women after menopause. The area under curve (AUC) (95%CI) for OC, OP, and ALP was 0.75 (0.668-0.8130), 0.75 (0.685-0.812), and 0.602 (0.524-0.670), respectively. ROC analysis indicated that at the cut-off point of 16.28 ng/mL, sensitivity and specificity were 70.3% and 70.9%, respectively, for OC. Furthermore, at the cut-off point of 28.85 ng/mL, the sensitivity of 70.3% and specificity of 66.6% were obtained for OP. The serum OC and OP were significantly related to hip and major osteoporotic fractures (P < 0.05). The higher serum concentration of OC, OP, and ALP had significant associations with lower BMD. These BTMs can be complementary tools and helpful in the postmenopausal period as measures for screening of bone loss and possible bone fracture.

Combined vitamin D and magnesium supplementation does not influence markers of bone turnover or glycemic control: A randomized controlled clinical trial

High-dose vitamin D supplementation can increase total osteocalcin concentrations that may reduce insulin resistance in individuals at risk for prediabetes or diabetes mellitus. Magnesium is a cofactor in vitamin D metabolism and activation. The purpose of this study was to determine the combined effect of vitamin D and magnesium supplementation on total osteocalcin concentrations, glycemic indices, and other bone turnover markers after a 12-week intervention in individuals who were overweight and obese, but otherwise healthy. We hypothesized that combined supplementation would improve serum total osteocalcin concentrations and glycemic indices more than vitamin D supplementation alone or a placebo. A total of 78 women and men completed this intervention in 3 groups: a vitamin D and magnesium group (1000 IU vitamin D3 and 360 mg magnesium glycinate), a vitamin D group (1000 IU vitamin D3), and a placebo group. Despite a significant increase in serum 25-hydroxyvitamin D concentrations in the vitamin D and magnesium group compared with the placebo group (difference=5.63; CI, -10.0 to -1.21; P=.001) post-intervention, there were no differences in serum concentrations of total osteocalcin, glucose, insulin, and adiponectin or the homeostatic model assessment of insulin resistance (HOMA-IR) among groups (P > .05 for all). Additionally, total osteocalcin (β=-0.310, P=.081), bone-specific alkaline phosphatase (β=0.004, P=.986), and C-terminal cross-linked telopeptide (β=0.426, P=.057), were not significant predictors of HOMA-IR after the intervention. Combined supplementation was not associated with short-term improvements in glycemic indices or bone turnover markers in participants who were overweight and obese in our study. This trial was registered at clinicaltrials.gov (NCT03134417).

Serum bone remodeling parameters and transcriptome profiling reveal abnormal bone metabolism associated with keel bone fractures in laying hens

Keel bone fractures affect welfare, health, and production performance in laying hens. A total of one hundred and twenty 35-wk-old Hy-line Brown laying hens with normal keel (NK) bone were housed in furnished cages and studied for ten weeks to investigate the underlying mechanism of keel bone fractures. At 45 wk of age, the keel bone state of birds was assessed by palpation and X-ray, and laying hens were recognized as NK and fractured keel (FK) birds according to the presence or absence of fractures in keel bone. The serum samples of 10 NK and 10 FK birds were collected to determine bone metabolism-related indexes and slaughtered to collect keel bones for RNA-sequencing (RNA-seq), Micro-CT, and histopathological staining analyses. The results showed that the concentrations of Ca, phosphorus, calcitonin, 25-hydroxyvitamin D3, and osteocalcin and activities of alkaline phosphatase and tartrate-resistant acid phosphatase (TRAP) in serum samples of FK birds were lower than those of NK birds (P < 0.05), but the concentrations of parathyroid hormone, osteoprotegerin, and corticosterone in serum samples of FK birds were higher than those of NK birds (P < 0.05). TRAP staining displayed that FK bone increased the number of osteoclasts (P < 0.05). Micro-CT analysis indicated that FK bone decreased bone mineral density (P < 0.05). Transcriptome sequencing analysis of NK and FK bones identified 214 differentially expressed genes (DEGs) (|log2FoldChange| > 1, P < 0.05), among which 88 were upregulated and 126 downregulated. Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) analysis indicated that 14 DEGs related to skeletal muscle movement and bone Ca transport (COL6A1, COL6A2, COL6A3, PDGFA, MYLK2, EGF, CAV3, ADRA1D, BDKRB1, CACNA1S, TNN, TNNC1, TNNC2, and RYR3) were enriched in focal adhesion and Ca signaling pathway, regulating bone quality. This study suggests that abnormal bone metabolism related to keel bone fractures is possibly responded to fracture healing in laying hens.

LBMON274 Total Osteocalcin Levels Are Independently Associated With Worse Testicular Function And A Higher Degree Of HPG Axis Activation In Klinefelter Syndrome

Abstract Context. Osteocalcin (OCN) is an osteoblast-produced polypeptide, emerging as the core element of the bone-testicular axis toghether with its undercarboxylated form (uOCN), proposed to increase testosterone (Te) levels in healthy men, by binding the Gpcr6a receptor on Leydig cells and modulating the GnRH pulse frequency and amplitude. However little is known with regards to its role in pubertal development and male hypogonadism. Objective and Design We investigated OCN concentrations in 47,XXY men affected by Klinefelter syndrome (KS), a model of adult hypergonadotropic hypogonadism, in a retrospective longitudinal study between 2007 and 2021 at an academic referral center. Patients and Methods 254 KS subjects, divided into the following groups: 1) pre-pubertal (n = 48, from 1 year of age until Tanner stage II), 2) pubertal (n = 46, Tanner stages II through V, &amp;lt;18 years), and 3) adults (n = 160, Tanner stage V, ≥18 years). All (pre-)pubertal patients were Te-naïve. Adult patients were categorized as: 1) eugonadal (total Te &amp;gt; 10.4 nmol/L; n = 47), 2) hypogonadal (Te &amp;lt; 10.4 nmol/L; n = 39), and 3) receiving testosterone replacement therapy (TRT) (n = 74). Data are presented as means ± SD, were tested with Brown-Forsythe and Welch ANOVA tests for unequal variances, corrected for multiple comparisons (Dunnett T3), and with partial correlations, after bootstrapping on 2000 samples. Main outcomes. Total serum OCN, hypothalamic-pituitary-gonadal (HPG) axis hormones (LH, FSH, total Te, 11β-estradiol, SHBG), and derived indexes. Results OCN levels varied throughout the life span, with a mean of 85.9±30.4 ng/mL in pre-pubertal infants, peaking at 130. 0±77.2 ng/mL in pubertal children (p = 0.243 vs pre-pubertal) and then declining to 22.9±9. 0 ng/mL in adults (p &amp;lt; 0. 001 vs pre-pubertal and pubertal). In (pre-)pubertal boys no correlation with HPG axis hormones was found. When comparing adult KS, OCN values were highest in eugonadal (26.5±10.4 ng/mL), slightly lower in hypogonadal (24.5±8.1 ng/mL, p = 0.268 vs eugonadal) and significantly lower in TRT subjects (20.4±8. 0 ng/mL, p = 0. 008 vs. eugonadal and = 0. 013 vs. hypogonadal). In adults, OCN correlated with both LH (r = 0.23, p = 0. 017) and FSH levels (r = 0.28, p = 0. 004). These significancies were maintained after the exclusion of subjects on TRT. Surprisingly, adjusting for age and BMI revealed significant inverse correlations with total Te (r = -0.44, p = 0. 004), calculated free Te (r = -0.37, p = 0. 016), the Te/LH (r = -0.40, p = 0. 010) and the calculated free Te/LH ratios (r = -0.33, p = 0. 031). These results were confirmed on a smaller sample with available uOCN levels. Conclusions In an experimental model of hypergonadotropic hypogonadism, OCN showed no association with gonadal function during normal pre-puberty and pubertal development. In adults, OCN levels were unexpectedly associated with worse testicular function and a higher degree of HPG stimulation. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Aroclor 1254 induced inhibitory effects on osteoblast differentiation in murine MC3T3-E1 cells through oxidative stress.

This study aimed to evaluate the osteotoxicity of polychlorinated biphenyls in murine osteoblastic MC3T3-E1 cells, and to explore the underlying mechanism focused on oxidative stress. The cells were exposed to Aroclor 1254 at concentrations of 2.5-20 µmol/L, and then cell viability, oxidative stress, intracellular calcium concentration, osteocalcin content, and calcium nodules formation were measured. Aroclor 1254 reduced cell viability and induced overproduction of intracellular reactive oxygen species in a dose-dependent manner. Activity of superoxide dismutase was decreased, and malondialdehyde content was promoted after exposure. Moreover, inhibitory effects of Aroclor 1254 on calcium metabolism and mineralization of osteoblasts were observed, as indicated by reduction of the intracellular calcium concentration, osteocalcin content, and modules formation rate. The decreased expression of osteocalcin, alkaline phosphatase, bone sialoprotein, and transient receptor potential vanilloid 6 further confirmed the impairment of Aroclor 1254 on calcium homeostasis and osteoblast differentiation. Addition of the antioxidant N-acetyl-L-cysteine partially restored the inhibitory effects on calcium metabolism and mineralization. In general, Aroclor 1254 exposure reduces calcium homeostasis, osteoblast differentiation and bone formation, and oxidative stress plays a vital role in the underlying molecular mechanism of osteotoxicity.

АССОЦИАЦИИ ПОЛИМОРФИЗМОВ RS1544410 И RS10735810 ГЕНА VDR С ОТДЕЛЬНЫМИ ПОКАЗАТЕЛЯМИ СЫВОРОТКИ КРОВИ В ДИНАМИКЕ ЛЕЧЕНИЯ ПОСТМЕНОПАУЗАЛЬНОГО ОСТЕОПОРОЗА

The role of VDR gene BsmI (rs1544410) and FokI (rs10735810) polymorphisms in postmenopausal osteoporosis formation has been confirmed by the results of fairly large number of studies. However, pharmacogenetic aspects of above polymorphisms have not been adequately studied. The aim of this work is to study the serum levels of certain biochemical parameters, bone turnover markers, vitamin D and parathyroid hormone in women with postmenopausal osteoporosis in the dynamics of treatment by ibandronic acid, depending on VDR gene rs1544410 and rs10735810 polymorphisms.&#x0D; We examined 117 women in dynamics of postmenopausal osteoporosis treatment. The 12-month course therapy included ibandronic acid, calcium and cholecalciferol according to the standard regimen. Detection of genetic polymorphisms was carried out by polymerase chain reaction method in real time. Twice, before the therapy start and at the end of one, the basic biochemical parameters, as well as β-Crosslaps, osteocalcin, 25(OH) D and parathyroid hormone were studied in women blood serum.&#x0D; Women with postmenopausal osteoporosis in treatment dynamics are characterized by significant decrease in serum β-CrossLaps, osteocalcin and alkaline phosphatase (p&lt;0.01), as well as an increase in 25(OH)D concentrations (p&lt;0.01). Prior to the initiation of therapy, GG genotype of the rs10735810 polymorphism of the VDR gene was associated with lower osteocalcin concentrations than in AA genotype (p&lt;0.01). Holders of GG genotype of VDR gene rs1544410 polymorphism, in comparison with other women, are characterized (p&lt;0.01) by lower levels of alkaline phosphatase (before treatment) and calcium (before and after treatment), higher levels of parathyroid hormone (before and after treatment).&#x0D; The obtained results can be used to develop personalized antiresorptive therapy regimens in postmenopausal osteoporosis.

Influence of Chinese Herbal Formula on Bone Characteristics of Cobb Broiler Chickens.

To evaluate the prevention and treatment effect of a Chinese herbal formula (CHF) on the bone disease of Cobb broiler chickens, compare its efficacy with Bisphosphonates (BPs), and provide a theoretical basis for studying the nutritional regulation technology of CHF to improve the bone characteristics of broiler chickens. In this study, 560 one-day-old Cobb broiler chickens were examined for the influence of Chinese herbal formula (CHF) and Bisphosphonates (BPs). Different doses of CHF and BPs were added to the diet, and the 30- and 60-day-old live weight, tibial bone strength, the microstructure of the distal femur cancellous bone, blood biochemical indexes related to bone metabolism, and genes related to bone metabolism were determined and analyzed. The results showed that the live weight of Cobb broilers fed with CHF and BPs in the diet was as follows: The live weight of the CHF group was higher than that of the normal control (NC) group, while the live weight of the BPs group was lower than that of the NC group; the CHF and BPs improved the bone strength of Cobb broilers and increased the elastic modulus, yield strength, and maximum stress of the tibia. CHF and BPs increased the cancellous bone mineral density (BMD), bone tissue ratio (BV/TV), bone surface area tissue volume ratio (BS/TV), bone trabecular thickness (Tb.Th), and bone trabecular number (Tb.N) in the distal femur, and decreased the bone surface area bone volume ratio (BS/BV) and bone trabecular separation (Tb.Sp). Thus, the microstructure of the bone tissue of the distal femur was improved to a certain extent. Both the CHF and the BPs also increased the serum levels of the vitamin D receptor (VDR), osteoprotegerin (OPG), and alkaline phosphatase (ALP), and decreased the content of osteocalcin (OT). Meanwhile, CHF and BPs upregulated the expression of osteogenic genes (BMP-2, OPG, Runx-2) to promote bone formation and downregulated the expression of osteoclastic genes (RANK, RANKL, TNF-α) to inhibit bone resorption, thus affecting bone metabolism. Conclusion: The CHF could improve the skeletal characteristics of Cobb broilers by upregulating the expression of bone-forming-related genes and downregulating the expression of bone-breaking-related genes, thus preventing and controlling skeletal diseases in Cobb broilers. Its effect was comparable to that of BPs. Meanwhile, the CHF-H group achieved the best results in promoting the growth and improvement of the skeletal characteristics of Cobb broilers based on the live weight and skeletal-characteristics-related indexes.

Electrospun PCL/fibrin scaffold as a bone implant improved the differentiation of human adipose-derived mesenchymal stem cells into osteo-like cells

Bone remodeling is not able to repair the major injuries caused by trauma, cancer, etc. Bone tissue engineering is aimed to provide implants for bone repair or replacement. To approach such a purpose, polymeric scaffolds along with stem cells are used to fabricate a supportive matrix mimicking in vivo microenvironment. Here, we developed an in vivo-like matrix based on polycaprolactone (PCL) and fibrin to enhance the differentiation of human adipose-derived mesenchymal stem cells into osteo-like cells (AD-MSCs). PCL scaffold was fabricated by electrospinning and coated with fibrin. AD-MSCs were cultured and differentiate on PCL and PCL/fibrin. The viability of cultured cells in comparison with tissue culture plate (TCPS) was evaluated by MTT assay on days 1, 2, and 3 of differentiation. The differentiation was compared to TCPS on days 7, 14, and 21 of differentiation. To evaluate the differentiation efficiency, calcium content, alkaline phosphatase (ALP), and expression of RUNX-2, Collagene-I, Osteocalcin, and Osteonectin were assessed in differentiated cells. A slight increase in cell viability was observed in the TCPS group on day 3 of differentiation. Higher calcium content and ALP activity were observed in PCL and PCL/fibrin groups, respectively. The expression of osteogenic genes was higher in the PCL/fibrin group on days 7, 14, and 21 of differentiation. It seems PCL acts synergistically with fibrin to make an in vivo-like microenvironment and enhanced the differentiation of AD-MSCs into osteo-like cells.

Osteogenic Differentiation of Human Umbilical Cord Blood Mesenchymal Stem Cells Induced by Liu's Zhenggudan No. 2 Formula.

Aim This study aimed to investigate the potential of Liu's Zhenggudan No. 2 Formula (LZF2) in inducing osteogenic differentiation of human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) and treating osteoporosis (OP), thereby providing new methods and ideas for the treatment of OP by traditional Chinese medicine. Methods Forty sample rats were equally divided into five groups: high-concentration LZF2, low-concentration LZF2, the Eucommia ulmoides (EU) group, the classical osteogenesis induction (COI) group, and the blank control group. Eight rats in each group were routinely housed for 7 days. Subsequently, to induce hUCB-MSCs, drug-containing serum was extracted from the abdominal aorta of rats to prepare the osteogenic induction solution. In addition, alkaline phosphatase (ALP) activity and osteocalcin (OCN) content assays, and alizarin red staining were performed on days 3, 6, 9, and 12 after culture. Results After induction of hUCB-MSCs, ALP activity and OCN content increased significantly in the high-concentration LZF2 group. Alizarin red staining also depicted numerous orange-red calcified nodules in rats in the high-concentration LZF2 group. Conclusion High concentration of LZF2 can facilitate the differentiation of hUCB-MSCs to promote osteogenesis.