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Clinical and Experimental Medicine Jun 2024Patients with systemic sclerosis (SSc) have a disproportionately high prevalence of reduced bone mineral density (BMD). Polymorphisms of the vitamin D receptor (VDR)...
Patients with systemic sclerosis (SSc) have a disproportionately high prevalence of reduced bone mineral density (BMD). Polymorphisms of the vitamin D receptor (VDR) gene have been associated with osteoporosis in patients with autoimmune diseases. The aim of this study was to investigate the prevalence and possible effects of VDR polymorphism on BMD and bone metabolism in patients with SSc. In patients with SSc measurement of BMD was performed using dual-energy X-ray absorptiometry. VDR polymorphisms (FokI, BsmI) were genotyped using restriction fragment length polymorphism analysis. Markers of bone metabolism (calcium, osteocalcin, β-crosslaps) were determined. Primary endpoint was the prevalence of VDR gene polymorphisms and the association with reduced BMD. Secondary endpoints included associations between bone metabolism and VDR gene polymorphism. 79 Caucasian patients with SSc were included. Overall, 83.5% had reduced BMD (51.9% osteopenia, 31.6% osteoporosis). The prevalence of VDR gene polymorphism (73% BsmI, 77% FokI) was comparable to studies in healthy and rheumatic populations. The homozygous presence of FokI polymorphism, but not BsmI, was significantly associated with reduced axial BMD. Fokl polymorphism was significantly associated with reduced CTX levels, although changes remained within the reference limits. VDR polymorphisms can frequently be found in patients with SSc in comparable prevalence to healthy and rheumatic populations. The homozygous presence of FokI polymorphism, but not BsmI, was significantly associated with reduced axial BMD. This could be a possible contributor for the high prevalence of reduced BMD in 83.5% of patients with SSc in this study.Trial registration. DRKS00032768, date: 05.10.2023, retrospectively registered.
Topics: Humans; Receptors, Calcitriol; Scleroderma, Systemic; Female; Bone Density; Male; Middle Aged; Aged; Adult; Prevalence; Osteoporosis; Absorptiometry, Photon; Polymorphism, Genetic; Polymorphism, Restriction Fragment Length; Bone Diseases, Metabolic; Genotype
PubMed: 38847864
DOI: 10.1007/s10238-024-01385-1 -
Biomolecules & Biomedicine Jun 2024Osteoporosis (OP) is a common chronic progressive bone disease that increases fracture risk in postmenopausal women. Research suggests that puerarin (Pue) may be an...
Osteoporosis (OP) is a common chronic progressive bone disease that increases fracture risk in postmenopausal women. Research suggests that puerarin (Pue) may be an effective treatment for OP. This study examined the effects and underlying mechanisms of Pue in treating postmenopausal osteoporosis (PMOP) in rats. Sprague-Dawley (SD) rats underwent bilateral ovariectomy to simulate PMOP and were then treated with subcutaneous injections of Pue. Bone mineral density (BMD) was measured using a bone densitometer. Micro-CT scans assessed femur bone structure and various parameters were calculated: bone volume fraction (BV/TV), bone surface density (BS/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular separation (Tb.Sp), and bone surface area-to-bone volume ratio (BS/BV). Hematoxylin-eosin (HE) staining was employed to observe femoral tissue pathology. Serum levels of bone formation metabolism-related markers-osteocalcin (OC), bone alkaline phosphatase (BALP), and procollagen type I N-terminal propeptide (PINP)-were measured via enzyme-linked immunosorbent assay (ELISA). The protein expression levels of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway in bone tissue were evaluated using Western blotting assay. The results showed improved bone density and reduced bone loss in rats treated with Pue. There were also significant increases in serum levels of OC and BALP, indicating enhanced osteogenesis. Furthermore, there was a decrease in activation of the JAK2/STAT3 pathway in femoral tissue, suggesting a pathway inhibition. These findings indicate that Pue may combat osteoporosis by promoting osteogenesis and inhibiting activation of the JAK2/STAT3 pathway activation.
PubMed: 38843496
DOI: 10.17305/bb.2024.10500 -
Cureus May 2024Physical activity significantly influences physiological biomarkers, including irisin and osteocalcin, which are pivotal for metabolic and bone health. Understanding the...
BACKGROUND
Physical activity significantly influences physiological biomarkers, including irisin and osteocalcin, which are pivotal for metabolic and bone health. Understanding the differential impacts of various exercise modalities on these biomarkers is essential for optimizing health benefits.
OBJECTIVES
The study aimed to compare the effects of endurance training and high-intensity resistance training (HIRT) on the levels of irisin and osteocalcin and determine which exercise modality more effectively influences these health-related biomarkers.
METHODS
The study was conducted at the Nimra Institute of Medical Sciences in Andhra Pradesh, India, where 100 healthy male participants aged between 21 and 35 were recruited. These participants, who were not regularly active and had no metabolic or bone diseases, were divided into two groups to undergo an eight-week training from March to April 2022. One group participated in endurance training involving running and cycling, while the other engaged in HIRT, both targeting a heart rate set at 75% of the maximum. Baseline and follow-up measurements of irisin and osteocalcin were taken before and after the training using blood samples collected after fasting. The study used paired t-tests to analyze changes in biomarker levels, and Pearson correlation coefficients to explore the relationship between the biomarkers, with results processed using statistical software and presented as mean ± standard deviation (SD).
RESULTS
Post-intervention, both exercise groups showed significant increases in irisin and a modest increase in osteocalcin levels. The HIRT group exhibited a higher increase in irisin levels (+119.33 pg/mL, p<0.015) compared to the endurance group (+108.32 pg/mL, p<0.023). Similarly, osteocalcin levels increased modestly in both groups, with the HIRT group showing a higher mean difference (+0.75 pg/mL, p<0.001) than the endurance group (+0.70 pg/mL). The study also found a link between changes in irisin and osteocalcin levels. This link was stronger in the HIRT group (r = +0.22; p < 0.039) than in the endurance group (r = +0.20; p < 0.038).
CONCLUSION
Both endurance and high-intensity resistance training are effective in enhancing metabolic and bone health, evidenced by increases in irisin and osteocalcin levels. Although the differences in mean values suggest that HIRT may have a marginal advantage in boosting these biomarkers, confirming the statistical significance of this difference is essential. Further research is required to understand the mechanisms behind these effects and to assess their long-term impacts on health and disease prevention.
PubMed: 38841020
DOI: 10.7759/cureus.59704 -
Clinical Oral Implants Research Jun 2024To determine whether combining cross-linked (CL) collagen-integrated xenogeneic bone blocks stabilized with the fixation of resorbable collagen membranes (CM) can...
OBJECTIVE
To determine whether combining cross-linked (CL) collagen-integrated xenogeneic bone blocks stabilized with the fixation of resorbable collagen membranes (CM) can enhance guided bone regeneration (GBR) in the overaugmented calvarial defect model.
MATERIALS AND METHODS
Four circular defects with a diameter of 8 mm were prepared in the calvarium of 13 rabbits. Defects were randomly assigned to receive one of the following treatments: (i) non-cross-linked (NCL) porcine-derived collagen-embedded bone block covered by a CM without fixation (NCL + unfix group); (ii) NCL bone block covered by CM with fixation using bone-tack (NCL + fix group); (iii) cross-linked (CL) porcine-derived collagen-embedded bone block covered by CM without fixation (CL + unfix group); and (iv) CL bone block covered by CM with fixation using bone-tack fixation (CL + fix group). The efficacy of GBR was assessed through histological and molecular analyses after 2 and 8 weeks.
RESULTS
At 2 weeks, there were no significant differences in histologically measured areas of newly formed bone among the groups. At 8 weeks, however, the CL + fix group exhibited a larger area of new bone (5.08 ± 1.09 mm, mean ± standard deviation) compared to the NCL + unfix (1.62 ± 0.42 mm; p < .0083), NCL + fix (3.97 ± 1.39 mm) and CL + unfix (2.55 ± 1.04 mm) groups. Additionally, the expression levels of tumour necrosis factor-alpha, fibroblast growth factor-2, vascular endothelial growth factor, osteocalcin and calcitonin receptor were significantly higher in the CL + fix group compared to the other three groups (p < .0083).
CONCLUSION
Cross-linked bone blocks stabilized with collagen membrane fixation can significantly enhance GBR.
PubMed: 38838049
DOI: 10.1111/clr.14309 -
Cellular and Molecular Biology... Jun 2024This experiment aimed to explore the influence mechanism of external fixator on open fracture. A total of 128 patients with open tibiofibular fractures were included in... (Randomized Controlled Trial)
Randomized Controlled Trial
This experiment aimed to explore the influence mechanism of external fixator on open fracture. A total of 128 patients with open tibiofibular fractures were included in this study. The patients were randomly divided into external fixator group (n=64) and control group (n=64) according to the order of admission. Double-blind controlled observation was used. The levels of osteocalcin (BGP), β-CTX, P1 NP, BALP, including haptoglobin (Hp), ceruloplasmin (CER), serum adrenocorticotropic hormone (ACTH), cortisol (COR), C-reactive protein (CRP), white blood cell (WBC) and interleukin-6 (IL-6) were recorded in different groups. The postoperative VAS score and quality of life were recorded. Log-rank was used to analyze the difference in postoperative adverse reaction rates among different groups. External fixation stent treatment increased BGP, PINP, and BALP expression and decreased β-CTX, Hp, CER, ACTH, COR, CRP, WBC, and IL-6 levels. Patients in the external fixation stent group had significantly lower VAS score quality of life scores and incidence of adverse events than the control group. External fixation stents protect open fracture patients by promoting bone metabolism.
Topics: Humans; Male; Female; Adult; External Fixators; Osteocalcin; Middle Aged; Bone and Bones; C-Reactive Protein; Quality of Life; Fractures, Open; Interleukin-6; Procollagen; Double-Blind Method; Collagen Type I; Adrenocorticotropic Hormone; Peptide Fragments; Extremities; Peptides; Hydrocortisone
PubMed: 38836683
DOI: 10.14715/cmb/2024.70.6.10 -
Cellular and Molecular Biology... Jun 2024Osteoporosis is a condition with reduced bone mass and disrupted architecture. Osteoporosis affects the Temporomandibular disorders (TMD) by changing bone density and...
Osteoporosis is a condition with reduced bone mass and disrupted architecture. Osteoporosis affects the Temporomandibular disorders (TMD) by changing bone density and quality. This study aims to determine the nature and extent of temporomandibular joint (TMJ) involvement in osteoporotic patients by correlating TMJ morphological changes detected by CBCT with systemic bone health indicated by BMD T-scores from DEXA and analyzing BTMs in serum and saliva. This study was a cross-sectional study conducted from May 2021 to December 2022. It involved 50 participants divided into two groups (N=25). One group was healthy male, while the other group had osteoporosis male. Saliva and blood samples were collected, and diagnostic imaging was conducted. The prevalence of various bone changes in the condyle was examined using CBCT. Erosion was found to be the most common, followed by Flattening, Osteophyte, and Subchondral cysts. The study group had significantly higher rates of smooth condyle, erosive lesions, and osteophytes compared to the control group. Pseudocyst decreased on the right side but increased on the left side. Pain on the right side increased more in the study group, and the T score for osteoporosis was higher in the study group. Joint spaces, condyle diameter, and glenoid cavity measurements differed significantly between sick and healthy people, as shown by CBCT (P≤0.001). Only the ALP parameter in the serum showed a significant increase in the study group compared to the control group. Saliva analysis revealed higher levels of calcium, osteocalcin, and ALP in the case group compared to the control group. The results of this study showed that CBCT as a specialized technique in imaging by providing detailed images can be used to evaluate osteoporosis and be used as an accurate diagnostic tool.
Topics: Humans; Male; Cross-Sectional Studies; Osteoporosis; Temporomandibular Joint; Middle Aged; Biomarkers; Saliva; Cone-Beam Computed Tomography; Bone Density; Aged; Adult; Temporomandibular Joint Disorders
PubMed: 38836666
DOI: 10.14715/cmb/2024.70.6.24 -
Journal of Orthopaedic Surgery and... Jun 2024The present study aimed to investigate the underlying mechanism of mechanical stimulation in regulating osteogenic differentiation.
OBJECTIVE
The present study aimed to investigate the underlying mechanism of mechanical stimulation in regulating osteogenic differentiation.
MATERIALS AND METHODS
Osteoblasts were exposed to compressive force (0-4 g/cm) for 1-3 days or CGRP for 1 or 3 days. Expression of receptor activity modifying protein 1 (RAMP1), the transcription factor RUNX2, osteocalcin, p38 and p-p38 were analyzed by western blotting. Calcium mineralization was analyzed by alizarin red straining.
RESULTS
Using compressive force treatments, low magnitudes (1 and 2 g/cm) of compressive force for 24 h promoted osteoblast differentiation and mineral deposition whereas higher magnitudes (3 and 4 g/cm) did not produce osteogenic effect. Through western blot assay, we observed that the receptor activity-modifying protein 1 (RAMP1) expression was upregulated, and p38 mitogen-activated protein kinase (MAPK) was phosphorylated during low magnitudes compressive force-promoted osteoblast differentiation. Further investigation of a calcitonin gene-related peptide (CGRP) peptide incubation, a ligand for RAMP1, showed that CGRP at concentration of 25 and 50 ng/ml could increase expression levels of RUNX2 and osteocalcin, and percentage of mineralization, suggesting its osteogenic potential. In addition, with the same conditions, CGRP also significantly upregulated RAMP1 and phosphorylated p38 expression levels. Also, the combination of compressive forces (1 and 2 g/cm) with 50 ng/ml CGRP trended to increase RAMP1 expression, p38 activity, and osteogenic marker RUNX2 levels, as well as percentage of mineralization compared to compressive force alone. This suggest that RAMP1 possibly acts as an upstream regulator of p38 signaling during osteogenic differentiation.
CONCLUSION
These findings suggest that CGRP-RAMP1/p38MAPK signaling implicates in osteoblast differentiation in response to optimal magnitude of compressive force. This study helps to define the underlying mechanism of compressive stimulation and may also enhance the application of compressive stimulation or CGRP peptide as an alternative approach for accelerating tooth movement in orthodontic treatment.
Topics: Osteoblasts; Cell Differentiation; Receptor Activity-Modifying Protein 1; p38 Mitogen-Activated Protein Kinases; Osteogenesis; Calcitonin Gene-Related Peptide; MAP Kinase Signaling System; Stress, Mechanical; Animals; Cells, Cultured; Core Binding Factor Alpha 1 Subunit; Signal Transduction; Osteocalcin
PubMed: 38825686
DOI: 10.1186/s13018-024-04805-w -
Food and Chemical Toxicology : An... Jul 2024Exposure to plastic-derived estrogen-mimicking endocrine-disrupting bisphenols can have a long-lasting effect on bone health. However, gestational exposure to bisphenol...
Exposure to plastic-derived estrogen-mimicking endocrine-disrupting bisphenols can have a long-lasting effect on bone health. However, gestational exposure to bisphenol A (BPA) and its analogue, bisphenol S (BPS), on offspring's bone mineralization is unclear. The effects of in-utero bisphenol exposure were examined on the offspring's bone parameters. BPA and BPS (0.0, 0.4 μg/kg bw) were administered to pregnant Wistar rats via oral gavage from gestational day 4-21. Maternal exposure to BPA and BPS increased bone mineral content and density in the offspring aged 30 and 90 days (P < 0.05). Plasma analysis revealed that alkaline phosphatase, and Gla-type osteocalcin were significantly elevated in the BPS-exposed offspring (P < 0.05). The expression of BMP1, BMP4, and their signaling mediators SMAD1 mRNAs were decreased in BPS-exposed osteoblast SaOS-2 cells (P < 0.05). The expression of extracellular matrix proteins such as ALPL, COL1A1, DMP1, and FN1 were downregulated (P < 0.05). Bisphenol co-incubation with noggin decreased TGF-β1 expression, indicating its involvement in bone mineralization. Altered mineralization could be due to dysregulated expression of bone morphogenetic proteins and signalling mediators in the osteoblast cells. Thus, bisphenol exposure during gestation altered growth and bone mineralization in the offspring, possibly by modulating the expression of Smad-dependent BMP/TGF-β1 signalling mediators.
Topics: Animals; Phenols; Benzhydryl Compounds; Female; Pregnancy; Rats, Wistar; Prenatal Exposure Delayed Effects; Calcification, Physiologic; Rats; Sulfones; Humans; Smad1 Protein; Alkaline Phosphatase; Maternal Exposure; Bone Morphogenetic Protein 4; Osteocalcin; Bone Morphogenetic Protein 1; Male; Osteoblasts; Bone Density; Endocrine Disruptors; Transforming Growth Factor beta1; Carrier Proteins
PubMed: 38821392
DOI: 10.1016/j.fct.2024.114772 -
Molecular Medicine Reports Aug 2024C1q/tumor necrosis factor‑related protein 3 (CTRP3) expression is markedly reduced in the serum of patients with osteoporosis. The present study aimed to investigate...
C1q/tumor necrosis factor‑related protein 3 (CTRP3) expression is markedly reduced in the serum of patients with osteoporosis. The present study aimed to investigate whether CTRP3 reduces bone loss in oophorectomy (OVX)‑induced mice via the AMP‑activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/nuclear factor E2‑related factor 2 (Nrf2) signaling pathway. Female C57BL/6J mice and MC3T3‑E1 cells were used to construct and models of osteoporosis, respectively. The left femurs of mice were examined using micro‑computed tomography scans and bone‑related quantitative morphological evaluation was performed. Pathological changes and the number of osteoclasts in the left femurs of mice were detected using hematoxylin and eosin, and tartrate‑resistant acid phosphatase (TRAP) staining. Runt‑related transcription factor‑2 (RUNX2) expression in the left femurs was detected using immunofluorescence analysis, and the serum levels of bone resorption markers (C‑telopeptide of type I collagen and TRAP) and bone formation markers [osteocalcin (OCN) and procollagen type 1 N‑terminal propeptide] were detected. In addition, osteoblast differentiation and calcium deposits were examined in MC3T3‑E1 cells using alkaline phosphatase (ALP) and Alizarin red staining, respectively. Moreover, , and expression levels were detected using reverse transcription‑quantitative PCR, and the expression levels of proteins associated with the AMPK/SIRT1/Nrf2 signaling pathway were detected using western blot analysis. The results revealed that globular CTRP3 (gCTRP3) alleviated bone loss and promoted bone formation in OVX‑induced mice. gCTRP3 also facilitated the osteogenic differentiation of MC3T3‑E1 cells through the AMPK/SIRT1/Nrf2 signaling pathway. The addition of an AMPK inhibitor (Compound C), SIRT1 inhibitor (EX527) or Nrf2 inhibitor (ML385) reduced the osteogenic differentiation of MC3T3‑E1 cells via inhibition of gCTRP3. In conclusion, gCTRP3 inhibits OVX‑induced osteoporosis by activating the AMPK/SIRT1/Nrf2 signaling pathway.
Topics: Animals; Sirtuin 1; Female; Mice; Signal Transduction; Osteoporosis; NF-E2-Related Factor 2; Ovariectomy; AMP-Activated Protein Kinases; Mice, Inbred C57BL; Osteoblasts; Cell Line; Osteoclasts; Disease Models, Animal; Femur; Osteogenesis
PubMed: 38818814
DOI: 10.3892/mmr.2024.13257 -
Colloids and Surfaces. B, Biointerfaces Aug 2024Amniotic membrane (AM) is an attractive source for bone tissue engineering because of its low immunogenicity, contains biomolecules and proteins, and osteogenic...
Amniotic membrane (AM) is an attractive source for bone tissue engineering because of its low immunogenicity, contains biomolecules and proteins, and osteogenic differentiation properties. Hydroxyapatite is widely used as bone scaffolds due to its biocompatibility and bioactivity properties. The aim of this study is to design and fabricate scaffold based on hydroxyapatite-coated decellularized amniotic membrane (DAM-HA) for bone tissue engineering purpose. So human amniotic membranes were collected from healthy donors and decellularized (DAM). Then a hydroxyapatite-coating was created by immersion in 10X SBF, under variable parameters of pH and incubation time. Hydroxyapatite-coating was characterized and the optimal sample was selected. Human adipose-derived mesenchymal stem cell behaviors were assessed on control, amniotic membrane, and coated amniotic membrane. The results of the SEM, MTT assay, and Live-Dead staining showed that DAM and DAM-HA support cell adhesion, viability and proliferation. Osteogenic differentiation was evaluated by assessment of alkaline phosphatase activity and expression of osteogenic markers. Maximum gene expression values compared to control occurred in 14 days for alkalin phosphatase, while the highest values for osteocalcin and osteopontin in 21 days. These gene expression values in DAM and DAM-HA for alkalin phosphatase is 6.41 and 8.47, for osteocalcin is 3.95 and 5.94 and for osteopontin is 5.59 and 9.9 respectively. The results of this study indicated DAM supports the survival and growth of stem cells. Also, addition of hydroxyapatite component to DAM promotes osteogenic differentiation while maintaining viability. Therefore, hydroxyapatite-coated decellularized amniotic membrane can be a promising choice for bone tissue engineering applications.
Topics: Humans; Durapatite; Osteogenesis; Amnion; Cell Differentiation; Cell Proliferation; Tissue Engineering; Adipose Tissue; Mesenchymal Stem Cells; Cell Survival; Cell Adhesion; Cells, Cultured; Tissue Scaffolds; Stem Cells; Alkaline Phosphatase
PubMed: 38810465
DOI: 10.1016/j.colsurfb.2024.113974