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Bone Aug 2024MicroRNAs (miRNAs) regulate osteogenic differentiation processes and influence the development of osteoporosis (OP). This study aimed to investigate the potential role...
BACKGROUND
MicroRNAs (miRNAs) regulate osteogenic differentiation processes and influence the development of osteoporosis (OP). This study aimed to investigate the potential role of miR-466 l-3p in OP.
METHODS
The expression levels of miR-466 l-3p and fibroblast growth factor 23 (FGF23) were quantified in the trabeculae of the femoral neck of 40 individuals with or without OP using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The impact of miR-466 l-3p or FGF23 expression on cell proliferation and the expression levels of runt-related transcription factor 2 (RUNX2), type I collagen (Col1), osteocalcin (OCN), osterix (OSX) and dentin matrix protein 1 (DMP1) was quantified in human bone marrow mesenchymal stem cells (hBMSCs) overexpressing miR-466 l-3p. Furthermore, alkaline phosphatase (ALP) staining and alizarin red staining were performed to measure ALP activity and the levels of calcium deposition, respectively. In addition, bioinformatics analysis, luciferase reporter assays, and RNA pull-down assays were conducted to explore the molecular mechanisms underlying the effects of miR-466 l-3p and FGF23 in osteogenic differentiation of hBMSCs.
RESULTS
The expression levels of miR-466 l-3p were significantly lower in femoral neck trabeculae of patients with OP than in the control cohort, whereas FGF23 levels exhibited the opposite trend. Furthermore, miR-466 l-3p levels were upregulated and FGF23 levels were downregulated in hBMSCs during osteogenic differentiation. Moreover, the high miR-466 l-3p expression enhanced the mRNA expression of RUNX2, Col1, OCN, OSX and DMP1, as well as cell proliferation, ALP activity, and calcium deposition in hBMSCs. FGF23 was found to be a direct target of miR-466 l-3p. FGF23 overexpression downregulated the expression of osteoblast markers and inhibited the osteogenic differentiation induced by miR-466 l-3p overexpression. qRT-PCR and Western blot assays showed that miR-466 l-3p overexpression decreased the expression levels of mRNAs and proteins associated with the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway, whereas FGF23 upregulation exhibited the opposite trend.
CONCLUSION
In conclusion, these findings suggest that miR-466 l-3p enhances the osteogenic differentiation of hBMSCs by suppressing FGF23 expression, ultimately preventing OP.
Topics: Humans; Osteogenesis; Mesenchymal Stem Cells; MicroRNAs; Cell Differentiation; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Female; Male; Cell Proliferation; Middle Aged; Signal Transduction; Osteoporosis; Bone Marrow Cells; Base Sequence
PubMed: 38735373
DOI: 10.1016/j.bone.2024.117123 -
Diagnostics (Basel, Switzerland) Apr 2024The study of BMD provides only partial information on bone health in patients undergoing TSH suppression therapy due to differentiated thyroid cancer (DTC). The...
Comparison of Bone Mineral Density and Trabecular Bone Score in Patients with and without Vertebral Fractures and Differentiated Thyroid Cancer with Long-Term Serum Thyrotrophin-Suppressed Therapy.
INTRODUCTION
The study of BMD provides only partial information on bone health in patients undergoing TSH suppression therapy due to differentiated thyroid cancer (DTC). The trabecular bone score (TBS), a new parameter assessing bone microarchitecture, is proposed for studying bone in this context. This study aimed to analyze their long-term use in patients with DTC.
METHODS
Bone mineral density (BMD) was measured by dual X-ray densitometry (DXA) and TBS was assessed with iNsigth software (version 2.0, MediImaps, France) in 145 postmenopausal patients with DTC. Vertebral fractures (VFs) were identified using a semi-quantitative X-ray method.
RESULTS
The BMD at the end of this study did not differ from the initial measurement. However, the TBS decreased from 1.35 ± 0.1 to 1.27 ± 0.1 ( = 0.002). Increased levels of PTH, osteocalcin, and bone alkaline phosphatase (BAP) were observed, suggesting enhanced bone remodeling. There was an increase in the prevalence of osteoporosis and osteopenia (40.6% and 16.5% to 46.6% and 18.6%, respectively). The proportion of patients with partially degraded and totally degraded TBS increased from 31% and 15.1% to 48.9% and 24.8% by the end of this study. Among the 30 patients with VFs, there were no significant differences in age, body mass index (BMI), calcium intake, alcohol consumption, smoking, radioiodine, therapy, or thyroid parameters compared to those without VFs. The odds ratio for VFs increased with osteopenia (OR 2.63). Combining TBS with BMD did not improve discrimination.
CONCLUSIONS
The TBS decreased while the BMD remained unchanged. The percentage of patients with osteoporosis and osteopenia, whether partially degraded or totally degraded, increased by the end of this study. The predominant discordance was found in partially degraded microarchitectures, with a higher proportion of osteopenic patients compared to those with normal or osteoporotic bone density. The AUC of the combination of TBS and BMD did not enhance discrimination. TBS, radioactive iodine therapy, and sedentary lifestyle emerged as the main distinguishing factors for DTC patients with VFs.
PubMed: 38732282
DOI: 10.3390/diagnostics14090868 -
Food Research International (Ottawa,... Jun 2024Biogenic nanoparticles are promising carriers to deliver essential minerals. Here, calcium-enriched polyphosphate nanoparticles (CaPNPs) with a Ca/P molar ratio > 0.5...
Biogenic nanoparticles are promising carriers to deliver essential minerals. Here, calcium-enriched polyphosphate nanoparticles (CaPNPs) with a Ca/P molar ratio > 0.5 were produced by Synechococcus sp. PCC 7002 in the growth medium containing 1.08 g/L CaCl, and had nearly spherical morphologies with a wide size distribution of 5-75 nm and strongly anionic surface properties with an average ζ-potential of -39 mV, according to dynamic light-scattering analysis, transmission and scanning electron microscopy, and energy-dispersive X-ray spectroscopy. The ex-vivo ligated mouse ileal loop assays found that calcium in CaPNPs was readily available to intestinal absorption via both ion channel-mediated and endocytic pathways, specifically invoking macropinocytic internalization, lysosomal degradation, and transcytosis. Rat oral pharmacokinetics revealed that CaPNPs had a calcium bioavailability approximately 100 % relative to that of CaCl and more than 1.6 times of that of CaCO. CaPNPs corrected the retinoic acid-induced increase in serum calcium, phosphorus, and bone-specific alkaline phosphatase, and decrease in serum osteocalcin, bone mineral content/density, and femoral geometric parameters with an efficacy equivalent to CaCl and markedly greater than CaCO. In contrast to CaCl, CaPNPs possessed desirable resistance against phytate's antagonistic action on calcium absorption in these ex vivo and in vivo studies. Overall, CaPNPs are attractive as a candidate agent for calcium supplementation, especially to populations on high-phytate diets.
Topics: Animals; Nanoparticles; Polyphosphates; Biological Availability; Mice; Phytic Acid; Calcium; Male; Microalgae; Rats; Intestinal Absorption; Rats, Sprague-Dawley
PubMed: 38729691
DOI: 10.1016/j.foodres.2024.114321 -
Frontiers in Neurology 2024Although effective antiretroviral therapy (ART) has improved the life expectancy of people with HIV (PWH), the prevalence of milder forms of HIV-associated...
BACKGROUND
Although effective antiretroviral therapy (ART) has improved the life expectancy of people with HIV (PWH), the prevalence of milder forms of HIV-associated neurocognitive disorders (HAND) persist, and it is associated with systemic and neuro-inflammatory processes that could impact other organ systems. However, the complex signaling mechanisms between the bone-kidney systems and the brain in HAND remain unknown. Extracellular vesicles (EVs) play a potential role in inter-organ communication and are involved in regulating cell activity in distant tissues. In this study, we examined whether levels of EVs from bone-and kidney-related cells associate with cognitive dysfunction and explored the relationship between kidney-bone EV axis in PWH experiencing cognitive deficits.
METHODS
EV subtypes were characterized in plasma from 61 PWH with either cognitive impairment (CI, = 53) or normal cognition (NC, = 8) based on the American Academy of Neurology criteria for HIV-associated dementia (HAD, = 11), minor cognitive motor disorder (MCMD, = 25) or asymptomatic neurocognitive impairment (ANI, = 17) by spectral flow cytometry. EVs were profiled with markers reflecting bone and kidney cell origin. A support vector machine learning-based model was employed for analyses of EV phenotypes to predict the cognitive dysfunction.
RESULTS
Plasma-EVs expressing osteocalcin, sclerostin, and nephrin were significantly higher in the cognitive impairment group compared to the normal cognition group. EVs bearing kidney cell markers correlated significantly with bone-derived EVs. A machine learning-based model, comprised of osteocalcin+, nephrin+, and CD24+ EVs predicted cognitive impairment in PWH on ART.
CONCLUSION
Our study reveals that neurocognitive impairment in PWH is associated with increased levels of plasma EVs enriched with the bone markers osteocalcin and sclerostin and the kidney marker nephrin, suggesting that these EV subtypes may be novel candidate biomarkers for disease-spanning neurocognitive dysfunction. Moreover, the relationship between bone-derived EVs with kidney-derived EVs may suggest their role in mediating inter-organ crosstalk in the pathogenesis of HIV-associated cognitive impairment.
PubMed: 38725641
DOI: 10.3389/fneur.2024.1383227 -
Journal of Periodontal & Implant Science Apr 2024The aim of this study was to evaluate the effects of Frondoside A (FA) on the osteogenic differentiation of human periodontal ligament (PDL) cells.
PURPOSE
The aim of this study was to evaluate the effects of Frondoside A (FA) on the osteogenic differentiation of human periodontal ligament (PDL) cells.
METHODS
Human PDL cells were cultured in osteogenic medium and treated with FA at concentrations of 0, 0.05, and 0.2 µM for 14 days. The expression levels of genes associated with osteogenic differentiation were assessed using quantitative real-time polymerase chain reaction analysis. Subsequently, RNA sequencing was performed to identify enriched gene sets following FA treatment. Alkaline phosphatase (ALP) activity was measured to confirm the osteogenic potential of FA.
RESULTS
Treatment with 0.2 µM FA significantly increased the expression levels of runt-related transcription factor 2 (), , and osteocalcin () at day 3, while also significantly elevating the expression of dentin sialophosphoprotein (), , , , and osterix () at day 14 (<0.017). Hallmark gene sets enriched during FA treatment were associated with the KRAS (normalized enrichment score [NES]=2.02, =0.000), interferon alpha (IFN-α) (NES=1.88, =0.001), IFN-γ (NES=1.85, <0.001), hypoxia (NES=1.79, =0.001), and p53 (NES=1.77, =0.001) signaling pathways. Additionally, treatment with 0.2 µM FA significantly intensified ALP staining at day 14 (<0.05).
CONCLUSIONS
Within the limitations of this study, FA treatment influenced periodontal regeneration by promoting the osteogenic differentiation of human PDL cells.
PubMed: 38725429
DOI: 10.5051/jpis.2303840192 -
Acta Biochimica Polonica 2024The study aimed to determine the osteointegration markers after dental implantation and evaluate their predictive value. The study was performed on 60 practically...
The study aimed to determine the osteointegration markers after dental implantation and evaluate their predictive value. The study was performed on 60 practically healthy persons who needed teeth rehabilitation using dental implants. The conical-shaped implants (CI) and hexagonal implants (HI) were used. The content of Osteopontin (OPN), Osteocalcin (OC), Alkaline Phosphatase (ALP), Osteoprotegerin (OPG), and nitric oxide (NO) was determined in patients' gingival crevicular fluid (GCF) and peri-implant sulcular fluid (PISF), collected 1, 3, and 6 months after implantation. During the 3-6 months of observation level of OPN increased in patients with CIs (<50 years > 50 years) and HIs (<50 years) (CI: <50 years F = 36.457, < 0.001; >50 years F = 30.104, < 0.001; HI < 50 years F = 2.246, < 0.001), ALP increased in patients with CIs (<50 years: F = 19.58, < 0.001; >50 years: F = 12.01; = 0.001) and HIs (<50 years) (F = 18.51, < 0.001), OC increased in patients <50 years (CI: F = 33.72, < 0.001; HI: F = 55.57, < 0.001), but in patients >50 years - on the 3 days month (CI: F = 18.82, < 0.001; HI: F = 26.26, < 0.001), but sharply decreased at the end of sixth month. OPG increased during 1-3 months of the observation in patients <50 years (CI: F = 4.63, = 0.037; HI: F = 2.8927, = 0.046), but at the end of the sixth month returned to the initial level; NO content in PISF increased in patients with CI (>50 years) during 1-6 months of the observation (F = 27.657, < 0.001). During the post-implantation period, age-related differences in osteointegration were observed. Patients <50 years old had relatively high levels of OPN, ALP, OC, and OPG in PISF, resulting in less alveolar bone destruction around dental implants and more intensive osteointegration. These indicators may be used as biological markers for monitoring implant healing. The process of osseointegration was more intense in CIs due to their comparatively high mechanical loading.
Topics: Humans; Middle Aged; Biomarkers; Female; Male; Osteoprotegerin; Gingival Crevicular Fluid; Alkaline Phosphatase; Osseointegration; Osteocalcin; Adult; Osteopontin; Prognosis; Dental Implants; Nitric Oxide; Dental Implantation; Time Factors
PubMed: 38721304
DOI: 10.3389/abp.2024.12433 -
International Journal of Biological... Jun 2024Femoral head necrosis is a debilitating disorder that typically caused by impaired blood supply to the hip joint. In this study, a novel injectable hydrogel based on...
Femoral head necrosis is a debilitating disorder that typically caused by impaired blood supply to the hip joint. In this study, a novel injectable hydrogel based on Oxidized Carboxymethyl Cellulose (OCMC)-Carboxymethyl Chitosan (CMCS) polymers containing an angiogenesis stimulator peptide (QK) with a non-toxic crosslinking interaction (Schiff based reaction) was synthesized to enhance angiogenesis following femoral head necrosis in an animal model. The physicochemical features of fabricated injectable hydrogel were analyzed by FTIR, swelling and degradation rate, rheometry, and peptide release. Also, the safety and efficacy were evaluated following an in vitro hydrogel injection study and an avascular necrosis (AVN) animal model. According to the results, the hydrogel exhibited an appropriate swelling ratio and water uptake (>90 %, 24 h) as well as a suitable degradation rate over 21 days accompanied by a continuous peptide release. Also, data showed that hydrogels containing QK peptide boosted the proliferation, differentiation, angiogenesis, and osteogenic potential of both Bone Marrow mesenchymal Stem Cells (BM-MSCs) and human umbilical vein endothelial cells (HUVECs) (****p < 0.0001 and ***p < 0.001, respectively). Furthermore, molecular and histological evaluations significantly demonstrated the overexpression of Runx2, Osteocalcin, Collagen I, VEGF and CD34 genes (**p < 0.01 and ***p < 0.001, respectively), and also femoral head necrosis was effectively prohibited, and more blood vessels were detected in defect area by OCMC-CMCS hydrogel containing QK peptide (bone trabeculae >9000, ***p < 0.001). In conclusion, the findings demonstrate that OCMC-CMCS-QK injectable hydrogel could be considered as an impressive therapeutic construct for femoral head AVN healing.
Topics: Chitosan; Hydrogels; Carboxymethylcellulose Sodium; Animals; Humans; Femur Head Necrosis; Human Umbilical Vein Endothelial Cells; Peptides; Osteogenesis; Mesenchymal Stem Cells; Cell Proliferation; Wound Healing; Injections; Neovascularization, Physiologic; Cell Differentiation; Male; Rabbits; Disease Models, Animal
PubMed: 38718991
DOI: 10.1016/j.ijbiomac.2024.132127 -
Orthopaedic Surgery Jun 2024The micro-nano structure of 3D-printed porous titanium (Ti) alloy with excellent performance in avoiding stress shielding and promoting bone tissue differentiation...
OBJECTIVES
The micro-nano structure of 3D-printed porous titanium (Ti) alloy with excellent performance in avoiding stress shielding and promoting bone tissue differentiation provides a new opportunity for the development of bone implants, but it necessitates higher requirements for bone tissue differentiation and the antibacterial properties of bone implants in clinical practice.
METHODS
This study investigated the preparation, antimicrobial properties, and osteogenesis-promoting ability of the 3D printed porous Ti alloy anodic oxidized Ag-carrying (Ag@3D-TiO) scaffolds. The 3D printed porous Ti alloy (3D-Ti), anodized 3D printed porous Ti alloy (3D-TiO), and Ag@3D-TiO scaffolds were synthesized using electron beam melting. The antimicrobial properties of the scaffolds were examined using antibacterial tests and their cytocompatibility was assessed using a cell proliferation assay and acridine orange/ethidium bromide (AO/EB) staining. In vitro cellular assays were used to investigate the effects of the scaffold microstructural features on cell activity, proliferation, and osteogenesis-related genes and proteins. In vivo animal experiments were used to evaluate the anti-inflammatory and osteogenesis-promoting abilities of the scaffolds.
RESULTS
The Ag@3D-TiO scaffolds exhibited sustained anti-microbial activity over time, enhanced cell proliferation, facilitated osteogenic differentiation, and increased extracellular matrix mineralization. In addition, alkaline phosphatase (ALP), collagen type I (COL-I), and osteocalcin (OCN)-related genes and proteins were upregulated. In vivo animal implantation experiments, the anti-inflammatory effect of the Ag@3D-TiO scaffolds were observed using histology, and a large amount of fibrous connective tissue was present around it; the Ag@3D-TiO scaffolds were more bio-compatible with the surrounding tissues compared with 3D-Ti and 3D-TiO; a large amount of uniformly distributed neoplastic bone tissue existed in their pores, and the chronic systemic toxicity test showed that the 3D-Ti, 3D-TiO, and Ag@3D-TiO scaffolds are biologically safe.
CONCLUSION
The goal of this study was to create a scaffold that exhibits antimicrobial properties and can aid bone growth, making it highly suitable for use in bone tissue engineering.
Topics: Titanium; Osteogenesis; Tissue Scaffolds; Silver; Animals; Printing, Three-Dimensional; Mice; Cell Proliferation; Cell Differentiation; Anti-Bacterial Agents; Porosity
PubMed: 38706035
DOI: 10.1111/os.14081 -
Journal For Immunotherapy of Cancer May 2024Skeletal morbidity in patients with cancer has a major impact on the quality of life, and preserving bone health while improving outcomes is an important goal of modern...
BACKGROUND
Skeletal morbidity in patients with cancer has a major impact on the quality of life, and preserving bone health while improving outcomes is an important goal of modern antitumor treatment strategies. Despite their widespread use in early disease stages, the effects of immune checkpoint inhibitors (ICIs) on the skeleton are still poorly defined. Here, we initiated a comprehensive investigation of the impact of ICIs on bone health by longitudinal assessment of bone turnover markers in patients with cancer and by validation in a novel bioengineered 3D model of bone remodeling.
METHODS
An exploratory longitudinal study was conducted to assess erum markers of bone resorption (C-terminal telopeptide, CTX) and formation (procollagen type I N-terminal propeptide, PINP, and osteocalcin, OCN) before each ICI application (programmed cell death 1 (PD1) inhibitor or programmed death-ligand 1 (PD-L1) inhibitor) for 6 months or until disease progression in patients with advanced cancer and no evidence of bone metastases. To validate the in vivo results, we evaluated osteoclast (OC) and osteoblast (OB) differentiation on treatment with ICIs. In addition, their effect on bone remodeling was assessed by immunohistochemistry, confocal microscopy, and proteomics analysis in a dynamic 3D bone model.
RESULTS
During the first month of treatment, CTX levels decreased sharply but transiently. In contrast, we observed a delayed increase of serum levels of PINP and OCN after 4 months of therapy. In vitro, ICIs impaired the maturation of preosteoclasts by inhibiting STAT3/NFATc1 signaling but not JNK, ERK, and AKT while lacking any direct effect on osteogenesis. However, using our bioengineered 3D bone model, which enables the simultaneous differentiation of OB and OC precursor cells, we confirmed the uncoupling of the OC/OB activity on exposure to ICIs by demonstrating impaired OC maturation along with increased OB differentiation.
CONCLUSION
Our study indicates that the inhibition of the PD1/PD-L1 signaling axis interferes with bone turnover and may exert a protective effect on bone by indirectly promoting osteogenesis.
Topics: Humans; Bone Remodeling; Male; Female; Prospective Studies; Immune Checkpoint Inhibitors; Middle Aged; Programmed Cell Death 1 Receptor; B7-H1 Antigen; Aged; Longitudinal Studies; Neoplasms; Adult
PubMed: 38702145
DOI: 10.1136/jitc-2023-008669 -
Iranian Journal of Public Health Jan 2024Leptin has a great effect on bone through direct or indirect involvement in bone remodeling. Considering the ambiguities that exist regarding the effect of leptin on... (Review)
Review
BACKGROUND
Leptin has a great effect on bone through direct or indirect involvement in bone remodeling. Considering the ambiguities that exist regarding the effect of leptin on bone and bone-related diseases including osteoporosis, in this study, we aimed to conduct a systematic review of various studies on the effect of leptin on osteoporosis, which may find an answer to the existing ambiguities.
METHODS
The search was performed to review studies on the effects of leptin on osteoporosis by using several databases including Scopus, PubMed, Web of Science, and Google Scholar. Electronic searches were conducted on 5 Jan 2023. There was no limit on the publication date of the articles. The risk of bias for the animal study was assessed with the CAMARADES checklist, and the study quality assessment was also assessed based on the guidelines for in vivo experiments (ARRIVE). In this study, the risk of bias (quality) of human studies was assessed using the quality assessment checklists by NHLBI.
RESULTS
Overall, 34 articles were included for data extraction and quality assessment. Overall, 27 human studies and seven animal studies were included in the article. The results of most of the studies conducted in this study showed that leptin has a physiological role in maintaining bone mass and better bone quality and reduces bone marrow adipogenesis and increases bone mineral density (BMD). As plasma leptin levels increased, BMD values or bone formation biomarkers increased.
CONCLUSION
Leptin has an inhibitory role against bone resorption and increasing osteoprotegerin (OPG) levels, which, as a result, maintains bone density and reduces osteoclast activity, and has a positive relationship with increasing osteocalcin.
PubMed: 38694865
DOI: 10.18502/ijph.v53i1.14686