Sildenafil Promotes Osteogenic Differentiation of Human Mesenchymal Stem Cells and Inhibits Bone Loss by Affecting the TGF-β Signaling Pathway

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Янв. 23, 2025

Background Osteoporosis, a common bone disorder, is primarily managed pharmacologically. However, existing medications are associated with non-trivial side-effects. Sildenafil, which already finds many clinical applications, promotes angiogenesis and cellular differentiation. Osteoporotic patients often exhibit reduced intraosseous vasculature impaired differentiation; sildenafil may thus usefully treat osteoporosis. Methods Here, the effects of on osteogenic differentiation human mesenchymal stem cells (hMSCs) were explored, as molecular mechanisms in play. We treated hMSCs varying concentrations measured cell proliferation in vitro. used mouse model subcutaneous ectopic osteogenesis to assess sildenafil's effect hMSC vivo. also explored loss tail-suspended (TS) ovariectomized (OVX) mice. Mechanistically, we employed RNA-sequencing define potentially relevant pathways. Results Low significantly enhanced optimal concentration be 10 mg/L. Sildenafil mitigated osteoporosis OVX TS probably promoted by acting transforming growth factor-β (TGF-β) signaling pathway. Conclusions In conclusion, low inhibited loss. Our findings offer new insights into physiological material.

Язык: Английский

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The association between lipid accumulation product and osteoporosis in American adults: analysis from NHANES dataset

Frontiers in Medicine, Год журнала: 2025, Номер 12

Опубликована: Март 19, 2025

Background The Lipid Accumulation Product (LAP), a novel indicator of fat accumulation, reflects the distribution and metabolic status body fat. This study aims to evaluate relationship between adult Americans’ prevalence osteoporosis LAP. Methods used data from NHANES cycles 2007–2010, 2013–2014, 2017–2018, including 4,200 adults aged 50 above. LAP was calculated using waist circumference triglyceride levels, whereas identified information dual-energy X-ray absorptiometry (DXA) assessments bone mineral density (BMD). Restricted cubic spline (RCS) analysis evaluated osteoporosis. Additionally, subgroup analyses were conducted assess impact demographic characteristics health on Results shown be significantly inversely correlated in study. In unadjusted model, Log showed significant negative connection (OR = 0.62, 95% CI 0.52–0.74). Osteoporosis decreased by 45% fully adjusted model for every unit rise 0.54, 0.44–0.66). RCS revealed nonlinear association ( P -non-linear 0.0025), showing an L-shaped correlation. Subgroup studies that, regardless age, sex, ethnicity, or condition, there constant Conclusion According this study, is substantial America easy-to-use practical indication that may very helpful prevention early detection.

Язык: Английский

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Sildenafil promotes osteogenic differentiation of human mesenchymal stem cells and inhibits bone loss by affecting the TGF-β signaling pathway

Stem Cell Research & Therapy, Год журнала: 2025, Номер 16(1)

Опубликована: Апрель 23, 2025

Osteoporosis, a common bone disorder, is primarily managed pharmacologically. However, existing medications are associated with non-trivial side-effects. Sildenafil, which already finds many clinical applications, promotes angiogenesis and cellular differentiation. Osteoporotic patients often exhibit reduced intraosseous vasculature impaired differentiation; sildenafil may thus usefully treat osteoporosis. Here, the effects of on osteogenic differentiation human mesenchymal stem cells (hMSCs) were explored, as molecular mechanisms in play. We treated hMSCs varying concentrations measured cell proliferation vitro. used mouse model subcutaneous ectopic osteogenesis to assess sildenafil's effect hMSC vivo. also explored loss tail-suspended (TS) ovariectomized (OVX) mice. Mechanistically, we employed RNA-sequencing define potentially relevant pathways. The appropriate significantly enhanced optimal concentration be 10 mg/L. Sildenafil mitigated osteoporosis OVX TS probably promoted by acting transforming growth factor-β (TGF-β) signaling pathway. In conclusion, inhibited loss. Our findings offer new insights into physiological medicine.

Язык: Английский

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Jaw osteoporosis: Challenges to oral health and emerging perspectives of treatment

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 177, С. 116995 - 116995

Опубликована: Июнь 24, 2024

Osteoporosis is a prevalent bone metabolic disease that poses significant challenge to global human health. Jaw osteoporosis, characterized by microstructural damage of the jaw resulting from various factors, one common manifestations this condition. Recent studies have demonstrated osteoporosis has multifaceted effects on oral health and can negatively impact conditions such as periodontitis, implantation, orthodontic treatment, wound healing. However, there are still some limitations in conventional treatment osteoporosis. For instance, while bisphosphonates enhance quality, they may also lead osteonecrosis jaw, which potential safety hazard diagnosis treatment. In recent years, considerable attention been focused improving pathological condition Treatment strategies gut microbial regulation, extracellular vesicles, molecular targeted therapy, herbal medicine, mechanical stimulation expected efficacy minimize adverse reactions. Therefore, understanding these exploring novel treatments for provide new insights maintenance This article reviews describes associated with current methods. It discusses emerging perspectives offering comprehensive overview challenges future directions managing

Язык: Английский

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Mesenchymal stem cells and their extracellular vesicles in bone and joint diseases: targeting the NLRP3 inflammasome

Human Cell, Год журнала: 2024, Номер 37(5), С. 1276 - 1289

Опубликована: Июль 10, 2024

Язык: Английский

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Isolation and characterization of bone mesenchymal cell small extracellular vesicles using a novel mouse model

Journal of Bone and Mineral Research, Год журнала: 2024, Номер 39(11), С. 1633 - 1643

Опубликована: Авг. 22, 2024

Abstract Extracellular vesicles (EVs) are key mediators of cell–cell communication and involved in transferring specific biomolecular cargo to recipient cells regulate their physiological functions. A major challenge the understanding EV function vivo is difficulty ascertaining origin particles. The recent development “Snorkel-tag,” which includes EV-membrane-targeted CD81 fused a series extra-vesicular protein tags, can be used mark EVs originating from source for subsequent isolation characterization. We developed an mouse model, termed “CAGS-Snorkel,” expresses Snorkel-tag under control Cre-lox system, crossed this with either Prx1-Cre (mesenchymal progenitors) or Ocn-Cre (osteoblasts/osteocytes) isolated Snorkel-tagged bone marrow plasma using magnetic bead affinity column. miRNA-sequencing was performed on EVs, although similar profiles were observed, few miRNAs metabolism (miR-106b-5p, miRs-19b-3p, miRs-219a-5p) enriched Ocn-derived relative Prx1-derived subpopulations. To characterize effects these small cell target, cultured stromal treated Prx1 Ocn mRNA-sequencing performed. Pathways ossification, development, extracellular matrix interactions regulated by both subpopulations, whereas pathways including advanced glycation end-products signaling uniquely subpopulation, underlying important biological subpopulations within microenvironment. These data demonstrate that CAGS-Snorkel model useful tool characterizing biology tissue-specific EVs. Moreover, while mesenchymal populations share common secretory profile, we uncover differences based stage osteoblastic differentiation may have consequences.

Язык: Английский

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Biology of Exfoliation of Plasma Membrane-Derived Vesicles and the Radiation Response: Historical Background, Applications in Biodosimetry and Cell-Free Therapeutics, and Quantal Mechanisms for Their Release and Function with Implications for Space Travel

Radiation Research, Год журнала: 2024, Номер 202(2)

Опубликована: Июль 10, 2024

This historical review of extracellular vesicles in the setting exposure to ionizing radiation (IR) traces our understanding how were initially examined and reported literature late 1970s (for secreted exosomes) early 1980s plasma membrane-derived, exfoliated vesicles) where we are now may be headed next decade. An emphasis is placed on biophysical properties vesicles, energy consumption role vesiculation as an essential component membrane turnover. The impact intercellular signal trafficking by vesicle surface intra-vesicular lipids, proteins, nucleic acids metabolites reviewed context biomarkers for estimating individual dose after radiation, pathogenesis disease development cell-free therapeutics. Since express both growth stimulatory inhibitory molecules, a hypothesis proposed consider superposition shared space entanglement molecules sources that external human cells. Implications this approach travel deep briefly discussed clinical disorders have been observed travel.

Язык: Английский

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Clinical challenges and considerations in pharmacotherapy of osteoporosis due to menopause

Expert Opinion on Pharmacotherapy, Год журнала: 2024, Номер 25(10), С. 1359 - 1372

Опубликована: Июль 2, 2024

Introduction Osteoporosis is a chronic systemic skeletal disorder characterized by compromised bone strength and an increased risk of fracture, with high prevalence worldwide. It associated negative quality life morbidity mortality. Postmenopausal women are more prone to develop osteoporosis, many them will suffer at least one fragility fracture along their lifetime.

Язык: Английский

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Retrotransposon SINEs in Age-Related Diseases: Mechanisms and Therapeutic Implications

Ageing Research Reviews, Год журнала: 2024, Номер 101, С. 102539 - 102539

Опубликована: Окт. 11, 2024

Язык: Английский

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MicroRNA expression profiling and potential biomarker exploration in BMSCs of osteoporosis patients based on high-throughput sequencing technology

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Окт. 31, 2024

Background Bone marrow mesenchymal stem cells (BMSCs) are core and their differentiation orientation directly manipulates the ongoing of osteoporosis (OP). MicroRNAs (miRNAs) momentously characterized molecular in BMSCs. However, leading pattern trait miRNAs OP remain vague mysterious. Full-scale research BMSCs-existed miRNA expression between normal conditions patients experiencing is only way for us to pinpoint effect miRNA, making rationally effectively utilize miRNA. Objective This review chiefly lies exploring, selecting, verifying, confirming biomarker by dissecting patterns, which offer diagnosis reference, monitor value, customized feature therapy developing related preparation, emerging prognosis indicators. Methods We gathered miRNA-seq datasets from human BMSCs detect Herein, we searched distinguished microRNA levels BMSCs, sifted distinctively existing microRNAs, sought preferentially expressed had knowledge target points biomarkers, boosted our awareness role development pharmaceutical preparation aimed at it. Results These manifested aberrant variation matched control cases, they mainly draw upon Wnt/β-catenin, MAPK, Notch pathways perform signal delivery, mediating osteogenesis, adipogenesis, balance these two kinds differentiated conversion, proliferation, migration, apoptosis, stemness, senescence biological chondrocytes osteoclasts. In addition, treatment based on in vitro trials combination with animal models defined application miRNA-linked therapy. Conclusion paper accorded proof as screening tools, confirmation guidance, means, prediction indicators OP, paved road clinical practice, pushed personalized remedies that break through regular remedies.

Язык: Английский

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