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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 -
Scientific Reports Apr 2019The G protein-coupled receptor class C, group 6, subtype A (GPRC6A) is suggested to have a physiological function in glucose and bone metabolism, although the precise...
The G protein-coupled receptor class C, group 6, subtype A (GPRC6A) is suggested to have a physiological function in glucose and bone metabolism, although the precise role lacks consensus due to varying findings in different knockout (KO) mouse models and inconsistent findings on the role of osteocalcin, a proposed GPRC6A agonist. We have further characterized a full locus GPRC6A KO model with respect to energy metabolism, including a long-term high-dose glucocorticoid metabolic challenge. Additionally, we analyzed the microarchitecture of tibiae from young, middle-aged and aged GPRC6A KO mice and wildtype (WT) littermates. Compared to WT, vehicle-treated KO mice presented with normal body composition, unaltered insulin sensitivity and basal serum insulin and glucose levels. Corticosterone (CS) treatment resulted in insulin resistance, abnormal fat accrual, loss of lean mass and suppression of serum osteocalcin levels in both genotypes. Interestingly, serum osteocalcin and skeletal osteocalcin mRNA levels were significantly lower in vehicle-treated GPRC6A KO mice compared to WT animals. However, WT and KO age groups did not differ in long bone mass and structure assessed by micro-computed tomography. We conclude that GPRC6A is not involved in glucose metabolism under normal physiological conditions, nor does it mediate glucocorticoid-induced dysmetabolism in mice. Moreover, GPRC6A does not appear to possess a direct, non-compensable role in long bone microarchitecture under standard conditions.
Topics: Animals; Blood Glucose; Body Composition; Cancellous Bone; Cortical Bone; Gene Expression Regulation; Genetic Loci; Genotype; Homeostasis; Mice; Mice, Inbred C57BL; Mice, Knockout; Osteocalcin; RNA, Messenger; Receptors, G-Protein-Coupled; Tibia
PubMed: 30979912
DOI: 10.1038/s41598-019-41921-8 -
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 -
BMC Musculoskeletal Disorders Aug 2019Treatment of anterior cruciate ligament injuries commonly involves the use of polyethylene terephthalate (PET) artificial ligaments for reconstruction. However, the...
BACKGROUND
Treatment of anterior cruciate ligament injuries commonly involves the use of polyethylene terephthalate (PET) artificial ligaments for reconstruction. However, the currently available methods require long fixation periods, thereby necessitating the development of alternative methods to accelerate the healing process between tendons and bones. Thus, we developed and evaluated a novel technique that utilizes silicate-substituted strontium (SrSiP).
METHODS
PET films, nano-coated with SrSiP, were prepared. Bone marrow mesenchymal cells (BMSCs) from femurs of male rats were cultured and seeded at a density of 1.0 × 10/cm onto the SrSiP-coated and non-coated PET film, and subsequently placed in an osteogenic medium. The osteocalcin concentration secreted into the medium was compared in each case. Next, PET artificial ligament, nano-coated with SrSiP, were prepared. BMSCs were seeded at a density of 4.5 × 10/cm onto the SrSiP-coated, and non-coated artificial ligament, and then placed in osteogenic medium. The osteocalcin and calcium concentrations in the culture medium were measured on the 8th, 10th, 12th, and 14th day of culture. Furthermore, mRNA expression of osteocalcin, alkaline phosphatase (ALP), bone morphogenetic protein-2 (BMP2), and runt-related transcription factor 2 (Runx2) was evaluated by qPCR. We transplanted the SrSiP-coated and non-coated artificial ligament to the tibiae of mature New Zealand white rabbits. Two months later, we sacrificed them and histologically evaluated them.
RESULTS
The secretory osteocalcin concentration in the medium on the film was significantly higher for the SrSiP group than for the non-coated group. Secretory osteocalcin concentration in the medium on the artificial ligament was also significantly higher in the SrSiP group than in the non-coated group on the 14th day. Calcium concentration on the artificial ligament was significantly lower in the SrSiP group than in the non-coated group on the 8th, 10th, 12th, and 14th day. In qPCR as well, OC, ALP, BMP2, and Runx2 mRNA expression were significantly higher in the SrSiP group than in the non-coated group. Newly formed bone was histologically found around the artificial ligament in the SrSiP group.
CONCLUSIONS
Our findings demonstrate that artificial ligaments using SrSiP display high osteogenic potential and thus may be efficiently used in future clinical applications.
Topics: Animals; Anterior Cruciate Ligament Injuries; Apatites; Bone-Implant Interface; Calcium; Cell Differentiation; Cells, Cultured; Coated Materials, Biocompatible; Culture Media; Disease Models, Animal; Humans; Male; Materials Testing; Mesenchymal Stem Cells; Nanostructures; Osseointegration; Osteocalcin; Osteogenesis; Polyethylene Terephthalates; Primary Cell Culture; Rabbits; Rats; Silicates; Strontium; Time Factors; Wound Healing
PubMed: 31472679
DOI: 10.1186/s12891-019-2777-8 -
European Journal of Oral Sciences Jan 1998While cementoblasts express a number of mineral-related proteins, including bone sialoprotein (BSP), osteopontin (OPN) and osteocalcin (OC), these proteins do not appear... (Comparative Study)
Comparative Study Review
While cementoblasts express a number of mineral-related proteins, including bone sialoprotein (BSP), osteopontin (OPN) and osteocalcin (OC), these proteins do not appear to be expressed by cells of the intermediate dental follicle/periodontal ligament (PDL). This information was utilized in an experimental strategy to isolate presumptive cementoblasts from the root surface of day 24 murine mandibular first molars. Using microscopic dissection techniques, molars were carefully extracted from their alveolar crypts and subjected to trypsin-collagenase digestion to remove adherent cells. Primary cultures were established and assayed for expression of proteins known to be expressed by cementoblasts at this timepoint in vivo (i.e. BSP, OPN, OC) and also an odontoblast-specific protein (i.e. DSP) to rule out contamination by pulpal cells. A subgroup of cells were found to express Type I collagen (89% of cells), BSP (46%), OPN (23%) and OC (30%); DSP was not detected within these cultures. We propose that cells within this heterogeneous population, which express this profile of osteogenic proteins, represent cementoblasts. The availability of a cementoblast cell line will make possible rigorous and controlled in vitro analysis of these cells and allow for determination of the unique characteristics of these cells not shared with other cells, particularly osteoblasts.
Topics: Animals; Cell Separation; Cells, Cultured; Collagen; Dental Cementum; Extracellular Matrix Proteins; Gene Expression; Integrin-Binding Sialoprotein; Mice; Osteoblasts; Osteocalcin; Osteopontin; Phenotype; Phosphoproteins; Protein Precursors; RNA, Messenger; Sialoglycoproteins
PubMed: 9541247
DOI: 10.1111/j.1600-0722.1998.tb02197.x -
Journal of Bone and Mineral Research :... Dec 2006Biochemical measurements of bone turnover provide an objective assessment of disease activity and the response to treatment. Alkaline phosphatase is the best... (Review)
Review
Biochemical measurements of bone turnover provide an objective assessment of disease activity and the response to treatment. Alkaline phosphatase is the best characterized of the bone turnover markers and reflects the extent and activity of Paget's disease. However, in addition to bone-specific alkaline phosphatase (Bone ALP), there is also osteocalcin (OC) and procollagen type 1 N-terminal propeptide (P1NP) as formation markers. A variety of telopeptides (C-terminal telopeptide of type I collagen, [CTX], N-telopeptide of type I collagen [NTX]) or cross-link breakdown products of type 1 collagen can be used to assess bone resorption. Total alkaline phosphatase (Total ALP), Bone ALP, and P1NP all perform similarly in diagnosis and in evaluating the response to treatment, but the general availability, low interassay variation, and inexpensiveness of Total ALP makes it the best test for routine use. Measurement of the biological variability of the different markers in stable, untreated Paget's disease indicates how great a change (critical difference) is needed to define a true alteration in disease activity. Bone ALP, P1NP, and NTX show the highest therapy induced change/critical difference ratio during antiresorptive treatment. Some of the resorption markers show more complex changes in response to treatment. Pyridinoline (PYD) or deoxypyridinoline (DPD) cross-links of type 1 collagen are excreted in urine either as free or as peptide bound moieties, but it is the latter which decrease by the greatest amount in response to bisphosphonate therapy. Newly formed type 1 collagen contains an aspartyl-glycine motif (alphaCTX), which undergoes spontaneous isoaspartyl formation to betaCTX as the bone ages. In untreated Paget's disease, the alphaCTX is raised proportionately more (16-fold) than betaCTX (3-fold) and decreases in response to bisphosphonate therapy to a greater extent than betaCTX (measured in the sCTX assay). As bisphosphonates have become more potent, the aim of treatment has shifted toward the achievement of a rate of bone turnover in the lower part of the reference range. This is important because the duration of remission of disease activity is strongly determined by the post treatment nadir bone turnover.
Topics: Alkaline Phosphatase; Biomarkers; Bone Remodeling; Humans; Osteitis Deformans; Osteocalcin; Peptides
PubMed: 17229003
DOI: 10.1359/jbmr.06s204 -
Journal of Korean Medical Science Mar 2021Osteocalcin is known to regulate energy metabolism. Recently, metabolic syndrome (MetS) has been found to be associated with reduced levels of osteocalcin in men, as...
BACKGROUND
Osteocalcin is known to regulate energy metabolism. Recently, metabolic syndrome (MetS) has been found to be associated with reduced levels of osteocalcin in men, as well as in postmenopausal women. The aim of this study was to investigate the association between serum osteocalcin and MetS in premenopausal women, compared with that in postmenopausal women.
METHODS
This cross-sectional study was based on 5,896 participants who completed a health screening examination. They were classified according to their menopausal status. Each group was subdivided into non-MetS and MetS groups according to the modified National Cholesterol Education Program-Adult Treatment Panel III criteria. Serum osteocalcin levels were measured using the electrochemiluminescence immunoassay.
RESULTS
Serum osteocalcin level was significantly lower in women with MetS than in those without MetS, after adjusting for confounders (14.12 ± 0.04 vs. 13.17 ± 0.13 [ = 0.004] in premenopausal women, and 20.34 ± 0.09 vs. 19.62 ± 0.21 [ < 0.001] in postmenopausal women), regardless of their menopausal status. Serum osteocalcin levels decreased correspondingly with an increasing number of MetS elements ( for trend < 0.001). Multiple regression analysis demonstrated that waist circumference (β = -0.085 [ < 0.001] and β = -0.137 [ < 0.001]) and hemoglobin A1c (β = -0.09 [ < 0.001] and β = -0.145 [ < 0.001]) were independent predictors of osteocalcin in premenopausal and postmenopausal women. Triglyceride levels were also independently associated with osteocalcin levels in premenopausal women (β = -0.004 [ < 0.013]). The odds ratio (OR) for MetS was significantly higher in the lowest quartile than in the highest quartile of serum osteocalcin levels after adjusting for age, alkaline phosphatase, uric acid, high sensitivity C-reactive protein, and body mass index in all women (OR, 2.00; 95% confidence interval [CI], 1.49-2.68) as well as in premenopausal (OR, 2.23; 95% CI, 1.39-3.58) and postmenopausal (OR, 2.01; 95% CI, 1.26-3.23) subgroups.
CONCLUSION
Lower serum osteocalcin concentrations were significantly associated with MetS in both premenopausal and postmenopausal women and were therefore independent of menopausal status.
Topics: Adult; Aged; Aged, 80 and over; Cross-Sectional Studies; Female; Glycated Hemoglobin; Humans; Metabolic Syndrome; Middle Aged; Osteocalcin; Postmenopause; Premenopause; Regression Analysis; Republic of Korea; Triglycerides; Waist Circumference; Young Adult
PubMed: 33650335
DOI: 10.3346/jkms.2021.36.e56 -
International Journal of Molecular... Feb 2023Regenerative therapy for tissues by mesenchymal stem cell (MSCs) transplantation has received much attention. The cluster of differentiation (CD)146 marker, a...
Regenerative therapy for tissues by mesenchymal stem cell (MSCs) transplantation has received much attention. The cluster of differentiation (CD)146 marker, a surface-antigen of stem cells, is crucial for angiogenic and osseous differentiation abilities. Bone regeneration is accelerated by the transplantation of CD146-positive deciduous dental pulp-derived mesenchymal stem cells contained in stem cells from human exfoliated deciduous teeth (SHED) into a living donor. However, the role of CD146 in SHED remains unclear. This study aimed to compare the effects of CD146 on cell proliferative and substrate metabolic abilities in a population of SHED. SHED was isolated from deciduous teeth, and flow cytometry was used to analyze the expression of MSCs markers. Cell sorting was performed to recover the CD146-positive cell population (CD146+) and CD146-negative cell population (CD146-). CD146 + SHED without cell sorting and CD146-SHED were examined and compared among three groups. To investigate the effect of CD146 on cell proliferation ability, an analysis of cell proliferation ability was performed using BrdU assay and MTS assay. The bone differentiation ability was evaluated using an alkaline phosphatase (ALP) stain after inducing bone differentiation, and the quality of ALP protein expressed was examined. We also performed Alizarin red staining and evaluated the calcified deposits. The gene expression of ALP, bone morphogenetic protein-2 (BMP-2), and osteocalcin (OCN) was analyzed using a real-time polymerase chain reaction. There was no significant difference in cell proliferation among the three groups. The expression of ALP stain, Alizarin red stain, ALP, BMP-2, and OCN was the highest in the CD146+ group. CD146 + SHED had higher osteogenic differentiation potential compared with SHED and CD146-SHED. CD146 contained in SHED may be a valuable population of cells for bone regeneration therapy.
Topics: Humans; CD146 Antigen; Cell Differentiation; Cell Proliferation; Cells, Cultured; Dental Pulp; Osteocalcin; Osteogenesis; Stem Cells; Tooth, Deciduous
PubMed: 36835460
DOI: 10.3390/ijms24044048 -
BMC Biotechnology Jan 2021Microcapsule is considered as a promising 3D microenvironment for Bone Tissue Engineering (BTE) applications. Microencapsulation of cells in an appropriate scaffold not...
BACKGROUND
Microcapsule is considered as a promising 3D microenvironment for Bone Tissue Engineering (BTE) applications. Microencapsulation of cells in an appropriate scaffold not only protected the cells against excess stress but also promoted cell proliferation and differentiation. Through the current study, we aimed to microcapsulate the human Dental Pulp Stem Cells (hDPSCs) and evaluated the proliferation and osteogenic differentiation of those cells by using MTT assay, qRT-PCR, Alkaline phosphatase, and Alizarine Red S.
RESULTS
The SEM results revealed that Alg/Gel microcapsules containing nHA showed a rough and more compact surface morphology in comparison with the Alg/Gel microcapsules. Moreover, the microencapsulation by Alg/Gel/nHA could improve cell proliferation and induce osteogenic differentiation. The cells cultured in the Alg/Gel and Alg/Gel/nHA microcapsules showed 1.4-fold and 1.7-fold activity of BMP-2 gene expression more in comparison with the control group after 21 days. The mentioned amounts for the BMP-2 gene were 2.5-fold and 4-fold more expression for the Alg/Gel and Alg/Gel/nHA microcapsules after 28 days. The nHA, addition to hDPSCs-laden Alg/Gel microcapsule, could up-regulate the bone-related gene expressions of osteocalcin, osteonectin, and RUNX-2 during the 21 and 28 days through the culturing period, too. Calcium deposition and ALP activities of the cells were observed in accordance with the proliferation results as well as the gene expression analysis.
CONCLUSION
The present study demonstrated that microencapsulation of the hDPSCs inside the Alg/Gel/nHA hydrogel could be a potential approach for regenerative dentistry in the near future.
Topics: Alginates; Alkaline Phosphatase; Calcium; Capsules; Cell Differentiation; Cell Proliferation; Dental Pulp; Durapatite; Gelatin; Gene Expression; Humans; Hydrogels; Nanostructures; Osteocalcin; Osteogenesis; Stem Cells; Tissue Engineering
PubMed: 33430842
DOI: 10.1186/s12896-020-00666-3 -
International Journal of Molecular... Oct 2021The present study aimed to investigate the effect of β‑receptor blocker propranolol on early osseointegration of pure titanium implants and the underlying molecular...
The present study aimed to investigate the effect of β‑receptor blocker propranolol on early osseointegration of pure titanium implants and the underlying molecular regulatory mechanisms. An implant osseointegration model using the tibial metaphysis of New Zealand rabbits was established. The rabbits were divided into control and low‑, medium‑ and high‑dose propranolol groups. The formation of implant osseointegration was detected by X‑ray scanning. Mesenchymal stem cells (MSCs) and osteoblasts (OBs) were isolated and cultured , isoproterenol was supplemented to simulate sympathetic action and propranolol was subsequently administrated. The effect of propranolol on cell proliferation and osteogenic differentiation were assessed by EdU, flow cytometry, alizarin red staining and alkaline phosphatase (ALP) detection. The expression levels of bone morphogenetic protein (BMP)2, RUNX family transcription factor (RunX)2, collagen (COL)‑1, osteocalcin (OCN) and β2‑adrenergic receptor (AR) were detected by immunofluorescence, reverse transcription‑quantitative PCR and western blot assay. Propranolol effectively promoted implant osseointegration , facilitated proliferation of OBs, inhibited proliferation of MSCs and enhanced osteogenic differentiation of OBs and MSCs. The calcium content and ALP activity of cells treated with propranolol were markedly higher than in the control group. Propranolol also elevated mRNA and protein expression levels of BMP2, RunX2, COL‑1 and OCN in tissue and cells, and decreased the expression of β2‑AR. The present study demonstrated that the β‑receptor blocker propranolol promoted osteogenic differentiation of OBs and MSCs and enhanced implant osseointegration. The present study provided a novel insight into the application and regulatory mechanisms of propranolol.
Topics: Animals; Bone Morphogenetic Protein 2; Cell Differentiation; Cell Proliferation; Cells, Cultured; Core Binding Factor Alpha 1 Subunit; Gene Expression Regulation; Male; Mesenchymal Stem Cells; Osseointegration; Osteoblasts; Osteocalcin; Osteogenesis; Propranolol; Rabbits; Receptors, Adrenergic, beta-2; Titanium
PubMed: 34414453
DOI: 10.3892/ijmm.2021.5024