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Journal of Dental Sciences Jan 2022Iloprost has been proposed as a potential biomaterial owing to angiogenic and odontogenic properties. However, the liquid form can limit its use during clinical...
BACKGROUND/PURPOSE
Iloprost has been proposed as a potential biomaterial owing to angiogenic and odontogenic properties. However, the liquid form can limit its use during clinical applications. Mineral trioxide aggregate (MTA) has been used for various dental applications in which cell-material interaction is essential. This study aimed to investigate additive effects of iloprost on the biological properties of MTA on the viability, attachment, migration and differentiation of human mesenchymal stem cells (hMSCs).
MATERIALS AND METHODS
Standardized human dentin disks were prepared. MTA was prepared by mixing distilled water or iloprost solution, and the lumen of the disks was filled with MTA or MTA-iloprost. hMSCs on disk alone and hMSCs on culture plates were used as controls. Cell viability and attachment were measured after 1, 7 and 14 days using AlamarBlue assay and scanning electron microscopy (SEM). Cell migration in MTA or MTA-iloprost extracts was determined using a wound-healing model.Osteogenic differentiation was evaluated by real-time reverse transcriptase polymerase chain reaction for alkaline phosphatase (ALP), bone sialoprotein (BSP), osteocalcin (OCN), and osteopontin (OSP) gene expressions after 7 and 14 days of osteogenic induction.
RESULTS
Cells on MTA-iloprost surface showed similar viability with MTA at 1 and 14 days but enhanced cellular viability and cell spreading compared to MTA at 7 days (p < 0.05). Cell migration was similar by MTA-iloprost and MTA extracts (p > 0.05). MTAiloprost significantly upregulated BSP, OCN and OSP expressions compared to MTA (p < 0.05).
CONCLUSION
The addition of iloprost to MTA improved the initial cell viability and osteogenic potential of hMSCs.
PubMed: 35028042
DOI: 10.1016/j.jds.2021.03.018 -
Scientific Reports Oct 2020Smoking is thought to be a risk factor for osteoporosis development; however, the consequences of stopping smoking for bone homeostasis remain unknown. Here we conducted... (Observational Study)
Observational Study
Smoking is thought to be a risk factor for osteoporosis development; however, the consequences of stopping smoking for bone homeostasis remain unknown. Here we conducted two separate human studies and show that bone mineral density was significantly lower in smokers than in non-smokers. The first was an observational study of pre- and post-menopausal healthy female smokers and non-smokers; the second included 139 current smokers determined to stop smoking. In the second study, levels of bone formation markers such as osteocalcin and uncarboxylated osteocalcin significantly increased after successful smoking cessation, as verified by significantly reduced levels of serum cotinine, a nicotine metabolite. Moreover, nicotine administration to mice reduced bone mineral density and significantly increased the number of osteoclasts in bone. Reduced bone mass phenotypes seen in nicotine-treated mice were significantly increased following nicotine withdrawal, an outcome accompanied by significantly reduced serum levels of tartrate-resistant acid phosphatase, a bone resorption marker. Taken together, our findings suggest that bone homeostasis is perturbed but can be rescued by smoking cessation.
Topics: Adult; Animals; Bone Density; Cotinine; Female; Homeostasis; Humans; Male; Mice, Inbred C57BL; Middle Aged; Nicotine; Osteocalcin; Osteoclasts; Osteogenesis; Osteoporosis; Risk Factors; Smoking; Smoking Cessation; Tartrate-Resistant Acid Phosphatase
PubMed: 33033284
DOI: 10.1038/s41598-020-73789-4 -
Frontiers in Endocrinology 2021Bone and skeletal muscle represent a single functional unit. We cross-sectionally investigated body composition, risk of fall and circulating osteocalcin (OC) isoforms...
BACKGROUND
Bone and skeletal muscle represent a single functional unit. We cross-sectionally investigated body composition, risk of fall and circulating osteocalcin (OC) isoforms in osteoporotic postmenopausal women to test the hypothesis of an involvement of OC in the bone-muscle crosstalk.
MATERIALS AND METHODS
Twenty-nine non-diabetic, non-obese, postmenopausal osteoporotic women (age 72.4 ± 6.8 years; BMI 23.0 ± 3.3 kg/m) underwent to: 1) fasting blood sampling for biochemical and hormone assays, including carboxylated (cOC) and uncarboxylated (uOC) osteocalcin; 2) whole-body dual energy X-ray absorptiometry (DXA) to assess total and regional body composition; 3) magnetic resonance imaging to determine cross-sectional muscle area (CSA) and intermuscular adipose tissue (IMAT) of thigh muscles; 4) risk of fall assessment through the OAK system.
RESULTS
Appendicular skeletal muscle index (ASMMI) was low in 45% of patients. Forty percent got a low OAK score, consistent with moderate-severe risk of fall, which was predicted by low legs lean mass and increased total fat mass. Circulating cOC levels showed significantly correlated with βCTx-I, lean mass parameters including IMAT, and OAK score. Fractured and unfractured women did not differ for any of the analyzed parameters, though cOC and uOC positively correlated with legs lean mass, OAK score and bone markers only in fractured women.
CONCLUSIONS
Data supported the relationship between OC and skeletal muscle mass and function in postmenopausal osteoporotic women. Serum cOC, but not uOC, emerges as mediator in the bone-muscle crosstalk. Circulating cOC and uOC levels may be differentially regulated in fractured and unfractured osteoporotic women, suggesting underlying differences in bone metabolism.
Topics: Accidental Falls; Aged; Aged, 80 and over; Biomarkers; Carboxylic Acids; Case-Control Studies; Cross-Sectional Studies; Female; Follow-Up Studies; Humans; Middle Aged; Muscle, Skeletal; Muscular Diseases; Osteocalcin; Osteoporosis, Postmenopausal; Prognosis; Protein Processing, Post-Translational; Risk Factors
PubMed: 34025583
DOI: 10.3389/fendo.2021.669704 -
Contemporary Clinical Dentistry 2022It is known that a large number of mediators involved in osteogenesis can influence bone development and repair; however, whether these mediators could be used as...
BACKGROUND
It is known that a large number of mediators involved in osteogenesis can influence bone development and repair; however, whether these mediators could be used as markers of bone maturity has yet to be determined.
AIM
To evaluate the expression of osteocalcin (OC) and Runt-related transcription factor 2 (Runx2) in bone biopsies obtained during the reconstruction of atrophic anterior maxillae using particulate bone xenografts with or without association of autogenous bone marrow aspirate concentrate (BMAC).
MATERIALS AND METHODS
Ten patients were distributed into two groups ( = 5), according to the type of grafting material used: Control group (CG), particulate bone xenograft alone, and test group (TG), particulate bone xenograft combined with BMAC. A bone specimen was removed from the graft area 4 months after grafting, before implant placement. The specimens were processed and submitted to immunohistochemical analysis for detection of OC and Runx2. Histomorphometry was used to ascertain the percentage of stained areas in both groups. The Wilcoxon Mann-Whitney -Test was used in the statistical analysis ( < 0.05).
RESULTS
The immunohistochemical analysis revealed a significantly higher OC expression in the TG than in the CG, namely 27.40 ± 1.34% and 11.40 ± 2.70%, respectively ( < 0.05), and a significantly higher Runx2 expression in the TG than in the CG, namely 2.80 ± 0.84% and 0.40 ± 0.55%, respectively ( < 0.05).
CONCLUSION
The OC and Runx2 expression levels were higher when BMAC was associated with the bone xenograft than when it was not.
PubMed: 36213846
DOI: 10.4103/ccd.ccd_723_20 -
Journal of Endocrinological... Jun 2022Osteocalcin (OC), an osteoblast-derived regulator of metabolic processes, and circulating early endothelial progenitor cells (EPC, CD34 - /CD133 + /KDR +)...
Osteocalcin-expressing endothelial progenitor cells and serum osteocalcin forms are independent biomarkers of coronary atherosclerotic disease severity in male and female patients.
PURPOSE
Osteocalcin (OC), an osteoblast-derived regulator of metabolic processes, and circulating early endothelial progenitor cells (EPC, CD34 - /CD133 + /KDR +) expressing OC (OC +) are potential candidates linking bone metabolism and the vasculature and might be involved in vascular atherosclerotic calcification. This study aimed at assessing the association of circulating levels of different OC forms and of EPCs count with disease severity in patients with documented coronary atherosclerosis (CAD).
METHODS
Patients (n = 59) undergoing coronary angiography were divided, according to stenosis severity, into (1) early coronary atherosclerosis (ECA) (n = 22), and (2) late coronary atherosclerosis (LCA) (n = 37). Total OC (TOC), carboxylated OC (cOC), undercarboxylated OC (unOC) were quantified by ELISA. EPC OC + count was assessed by flow cytometry.
RESULTS
EPC OC + counts showed significant differences between ECA and LCA groups. unOC and unOC/TOC ratio were inversely correlated with EPC OC + count. A significant decrease in TOC and unOC plasma levels was associated with higher cardiovascular risk factors (CVRFs) number. EPC OC + count was correlated with LDL-C, total cholesterol, and triglycerides, with a greater significance in the LCA group. No association between the different forms of circulating OC (TOC, ucOC, cOC) and severity of CAD was found.
CONCLUSION
This study showed a significant association between EPCs (CD34 - /CD133 + /KDR + /OC +), CAD severity and CVRFs, suggesting an active role for EPC OC + in the development of CAD. An inverse correlation between TOC, ucOC, and number of CVRFs was observed, suggesting that OC, regardless of its carboxylation status, may be developed as a further cardiovascular risk biomarker.
Topics: Antigens, CD34; Biomarkers; Coronary Artery Disease; Endothelial Progenitor Cells; Female; Humans; Male; Osteocalcin; Severity of Illness Index
PubMed: 35089541
DOI: 10.1007/s40618-022-01744-3 -
The Journal of International Medical... Dec 2022The primary aim of this retrospective observational clinical study was to explore the risk factors for fracture in patients with fibrous dysplasia (FD) of the proximal... (Observational Study)
Observational Study
OBJECTIVE
The primary aim of this retrospective observational clinical study was to explore the risk factors for fracture in patients with fibrous dysplasia (FD) of the proximal femur.
METHODS
We investigated body mass index, bilateral radiographs on both sides, femoral neck shaft angle measurements, and markers of bone metabolism in patients with FD of the proximal femur according to whether or not they had sustained a hip fracture. Nine clinical parameters (age, sex, clinical classification, anatomic classification, femoral neck shaft angle, and procollagen type 1 N-terminal propeptide, C-terminal telopeptide of type I collagen, and osteocalcin levels) were selected for univariate analysis. Factors that were significant in univariate analysis were then subjected to multivariate logistic analysis.
RESULTS
Clinical classification, anatomic classification, femoral neck shaft angle, and the osteocalcin level were identified to be statistically significant risk factors for fracture in univariate analysis. Anatomic classification, femoral neck shaft angle, and the osteocalcin level remained significant risk factors in multivariate analysis.
CONCLUSIONS
Anatomic classification, femoral neck shaft angle, and the osteocalcin level are important risk factors for fracture in patients with FD of the proximal femur and could be used to guide implementation of a fracture prevention strategy in these patients.
Topics: Humans; Retrospective Studies; Research Design; Risk Factors
PubMed: 36482682
DOI: 10.1177/03000605221142395 -
Regenerative Therapy Dec 2022Circular RNAs (circRNAs) play a crucial regulatory role in human diseases. However, the roles of circRNAs in ankylosing spondylitis (AS) are barely known. In this study,...
BACKGROUND
Circular RNAs (circRNAs) play a crucial regulatory role in human diseases. However, the roles of circRNAs in ankylosing spondylitis (AS) are barely known. In this study, the functions of circ_0018168 in AS were investigated.
METHODS
Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot assay were used for circ_0018168, microRNA-330-3p (miR-330-3p), dickkopf-1 (DKK1), alkaline phosphatase (ALP), osteocalcin (OCN), Runt-related transcription factor 2 (Runx2) levels. Cell Counting Kit-8 (CCK-8) assay and 5'-ethynyl-2'-deoxyuridine (EdU) assay were conducted to analyze cell proliferation ability. Flow cytometry analysis was manipulated for cell cycle process. ALP activity was examined with a commercial kit. RNA immunoprecipitation (RIP) assay, RNA pull-down assay and dual-luciferase reporter assay were used to analyze the relationships of circ_0018168, miR-330-3p and DKK1.
RESULTS
Circ_0018168 and DKK1 levels were lowly expressed in AS hip capsule specimens. Circ_0018168 overexpression repressed cell proliferation, cell cycle process as well as reduced ALP activity and ALP, OCN and Runx2 protein levels in AS fibroblasts. DKK1 silencing ameliorated the impact of circ_0018168 on AS progression. In addition, circ_0018168 served as the sponge for miR-330-3p, which could target DKK1. MiR-330-3p inhibition suppressed the proliferation, cell cycle and osteogenic differentiation in AS fibroblasts, but DKK1 silencing reversed the impacts. Besides, the effect of circ_0018168 on AS development was abolished by miR-330-3p upregulation.
CONCLUSION
Circ_0018168 overexpression restrained fibroblast proliferation and osteogenic differentiation in AS by elevating DKK1 through adsorbing miR-330-3p.
PubMed: 35891711
DOI: 10.1016/j.reth.2022.06.005 -
International Journal of Endocrinology 2021Previous studies found that thyroid hormones stimulate osteoblast-like cells to secrete osteocalcin. We aimed to investigate the association between serum thyroid...
Previous studies found that thyroid hormones stimulate osteoblast-like cells to secrete osteocalcin. We aimed to investigate the association between serum thyroid hormone and serum osteocalcin in euthyroid population. The study recruited 1152 community-based euthyroid subjects (average age 59 ± 8 years), among whom 677 were women. Serum free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), and osteocalcin were measured by electrochemiluminescence immunoassays. After adjusting for age and gender, partial correlation analysis showed that FT3 and FT3/FT4 were both positively correlated with body mass index (BMI) and serum osteocalcin levels (all < 0.05) and BMI was negatively correlated with serum osteocalcin levels ( < 0.01), while FT4 and TSH were not correlated with serum osteocalcin levels (all > 0.05). Age, gender, blood pressure, thyroid hormones, and multiple metabolic risk factors were included in the ridge regression model. FT3 and FT3/FT4 were independently and positively associated with serum osteocalcin levels (all < 0.05), while BMI was independently and negatively associated with serum osteocalcin levels ( < 0.01). The mediating effect model showed that FT3 and FT3/FT4 suppressed the negative association between BMI and serum osteocalcin levels, with suppressing effects of 6.41% and 10.39%, respectively. In euthyroid subjects, both FT3 and FT3/FT4 were positively associated with serum osteocalcin levels, and they further suppressed the negative association between BMI and serum osteocalcin levels.
PubMed: 33628237
DOI: 10.1155/2021/6624516 -
International Journal of... 2021Although a number of studies have shown that the occurrence and progression of osteoarthritis (OA) is related to endocrine system dysfunction, there is limited evidence...
Although a number of studies have shown that the occurrence and progression of osteoarthritis (OA) is related to endocrine system dysfunction, there is limited evidence about what roles sex hormones play. The aim of the present study was to examine the capacity of 17β-estradiol (ED) and follicle stimulating hormone (FSH) to alter the differentiation of bone marrow (BM) cells in arthritic mice. The experiments were conducted in collagenase-induced osteoarthritis in mice. Cartilage degradation was observed by safranin and toluidine blue staining. Flow cytometry was used to define different BM and synovial cell populations. The influence of FSH and ED on osteoclastogenesis was studied in BM cultures and on the osteoblastogenesis in primary calvarial cultures. The levels of IL-8, TNF-α, FSH, and osteocalcin were estimated by ELISA. FSH increased cartilage degradation and serum osteocalcin levels, while ED abolished it and lowered serum osteocalcin. FSH elevated the percentage of monocytoid CD14+/RANK+ and B cell CD19+/RANK+ cells in contrast to ED which inhibited the accumulation of these osteogenic populations. Also, ED changed the percentage of CD105+/F4/80+ and CD11c+ cells in the synovium. FSH augmented and ED suppressed macrophage colony-stimulating factor (M-CSF) + receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast (OC) formation, and this correlated with a respective increase and decrease of IL-8 secretion. FSH did not influence osteoblast (OB) formation while ED enhanced this process in association with changes of TNF-α, IL-8, and osteocalcin production. ED reduced osteoclast generation in bone. The key outcome of the current study is that both hormones influenced BM cell differentiation, with FSH favoring osteoclast formation and ED favoring osteoblast accumulation.
Topics: Animals; Bone Marrow Cells; Cartilage, Articular; Cell Differentiation; Cells, Cultured; Estradiol; Female; Follicle Stimulating Hormone; Interleukin-8; Joints; Mice, Inbred ICR; Osteoarthritis; Osteoblasts; Osteocalcin; Tumor Necrosis Factor-alpha; Mice
PubMed: 34024188
DOI: 10.1177/20587384211016198 -
Biomolecules Feb 2021The aim of this study was to assess the associations of serum and bone zinc (Zn) and cuprum (Cu) with bone mineral density (BMD) and content (BMC), markers of bone...
The aim of this study was to assess the associations of serum and bone zinc (Zn) and cuprum (Cu) with bone mineral density (BMD) and content (BMC), markers of bone turnover, and sex hormones. The study group comprised 144 men treated with total hip replacement due to hip osteoarthritis. We measured total, free, and bioavailable testosterone, estradiol, and sex-hormone-binding globulin (sex hormones), as well as parathyroid hormone, osteocalcin, carboxy terminal collagen crosslinks, and N-terminal propeptide of type I procollagen (markers of bone turnover). Total body BMD, BMC, total and visceral fat, and appendicular skeletal mass (ASM) were measured using dual-energy X-ray absorptiometry. ASM index, and total and visceral fat were positively correlated with BMD. Bone Zn correlated neither with sex hormones nor with bone turnover markers; however, it was positively associated both with BMD and with BMC, while bone Cu (as opposed to serum Cu) was not. In multiple regression, the ASM index, Zn/Cu ratio (in both the serum and the bone), and serum Cu concentration were significantly associated with BMD and BMC after adjustment for age and body mass index (BMI). Our results suggest that the Zn/Cu ratio in both the serum and the bone may exert a significant positive effect on total BMD and BMC.
Topics: Absorptiometry, Photon; Aged; Arthroplasty, Replacement, Hip; Biomarkers; Body Mass Index; Bone Density; Bone Remodeling; Bone and Bones; Collagen; Copper; Estradiol; Humans; Male; Middle Aged; Osteocalcin; Parathyroid Hormone; Sex Hormone-Binding Globulin; Testosterone; Zinc
PubMed: 33567585
DOI: 10.3390/biom11020237