Molecular and Cellular Mechanisms of Osteoporosis

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(21), P. 15772 - 15772

Published: Oct. 30, 2023

Osteoporosis is a widespread systemic disease characterized by decrease in bone mass and an imbalance of the microarchitecture tissue. Experimental clinical studies devoted to investigating main pathogenetic mechanisms osteoporosis revealed important role estrogen deficiency, inflammation, oxidative stress, cellular senescence, epigenetic factors development resorption due osteoclastogenesis, decreased mineralization tissue formation reduced function osteoblasts caused apoptosis age-depended differentiation osteoblast precursors into adipocytes. The current review was conducted describe basic at molecular levels elucidate most promising therapeutic strategies therapy based on articles cited PubMed up September 2023.

Language: Английский

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Luteolin rescues postmenopausal osteoporosis elicited by OVX through alleviating osteoblast pyroptosis via activating PI3K-AKT signaling

Phytomedicine, Journal Year: 2024, Volume and Issue: 128, P. 155516 - 155516

Published: March 16, 2024

Recently, osteoblast pyroptosis has been proposed as a potential pathogenic mechanism underlying osteoporosis, although this remains to be confirmed. Luteolin (Lut), flavonoid phytochemical, plays critical role in the anti-osteoporosis effects of many traditional Chinese medicine prescriptions. However, its protective impact on osteoblasts postmenopausal osteoporosis (PMOP) not elucidated. This research aimed determine effect Lut ameliorating PMOP by alleviating and sustaining osteogenesis. was designed investigate novel both cell animal models. Ovariectomy-induced models were established mice with/without daily gavaged 10 or 20 mg/kg body weight Lut. The bone microstructure, metabolism oxidative stress evaluated with 0.104 Estradiol Valerate Tablets positive control. Network pharmacological analysis molecular docking employed mechanisms treatment. Subsequently, impacts PI3K/AKT axis, stress, mitochondria, assessed. In vitro, cultured (MC3T3-E1(14) cells exposed H2O2 examine signaling pathway, osteogenic differentiation, mitochondrial function, pyroptosis. Our findings demonstrated that Lut, similar control drug, effectively reduced systemic loss enhanced induced ovariectomy. indicated axis target, response nuclear membrane function being key mechanisms. Consequently, investigated. vivo data revealed deactivated following ovariectomy, restored phosphorylation proteins, thereby reactivating axis. Additionally, alleviated abnormalities intervention mitigated inhibition osteogenesis, well H2O2-induced Furthermore, attenuated ROS accumulation dysfunction. including osteogenesis restoration, anti-pyroptosis, maintenance, all reversed LY294002 (a pathway inhibitor). summary, could improve dysfunction, alleviate GSDME-mediated maintain via activating PI3K/Akt offering new therapeutic strategy for PMOP.

Language: Английский

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Crosstalk Between the Neuroendocrine System and Bone Homeostasis

Endocrine Reviews, Journal Year: 2023, Volume and Issue: 45(1), P. 95 - 124

Published: July 17, 2023

Abstract The homeostasis of bone microenvironment is the foundation health and comprises 2 concerted events: formation by osteoblasts resorption osteoclasts. In early 21st century, leptin, an adipocytes-derived hormone, was found to affect through hypothalamic relay sympathetic nervous system, involving neurotransmitters like serotonin norepinephrine. This discovery has provided a new perspective regarding synergistic effects endocrine systems on skeletal homeostasis. Since then, more studies have been conducted, gradually uncovering complex neuroendocrine regulation underlying Intriguingly, also considered as organ that can produce regulatory factors in turn exert activities. After decades exploration into mechanisms, separate bioactive extensively investigated, whereas few systematically shown global view regulation. Therefore, we summarized previously studied patterns from system bone. review will provide readers with panoramic intimate relationship between bone, compensating for current understanding homeostasis, probably developing therapeutic strategies its related disorders.

Language: Английский

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Exogenous melatonin ameliorates steroid-induced osteonecrosis of the femoral head by modulating ferroptosis through GDF15-mediated signaling

Stem Cell Research & Therapy, Journal Year: 2023, Volume and Issue: 14(1)

Published: July 3, 2023

Abstract Background Ferroptosis is an iron-related form of programmed cell death. Accumulating evidence has identified the pathogenic role ferroptosis in multiple orthopedic disorders. However, relationship between and SONFH still unclear. In addition, despite being a common disease orthopedics, there no effective treatment for SONFH. Therefore, clarifying mechanism investigating pharmacologic inhibitors from approved clinical drugs strategy translation. Melatonin (MT), endocrine hormone that become popular dietary supplement because its excellent antioxidation, was supplemented external source to treat glucocorticoid-induced damage this study. Methods Methylprednisolone, commonly used glucocorticoid clinic, selected simulate injury current observed through detection ferroptosis-associated genes, lipid peroxidation mitochondrial function. Bioinformatics analysis performed explore melatonin receptor antagonist shGDF15 were applied block therapeutic effect MT further confirm mechanism. Finally, experiments rat model detect effects MT. Results alleviated bone loss rats by maintaining BMSC activity suppression ferroptosis. The results are verified MT2 can bioinformatic subsequent confirmed growth differentiation factor 15 (GDF15), stress response cytokine, downregulated process On contrary, increased expression GDF15 marrow mesenchymal stem cells. Lastly, rescue with plays key melatonin. Conclusions We proposed attenuated inhibiting regulation GDF15, supplementation exogenous might be promising method Graphical

Language: Английский

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Unraveling the molecular and immunological landscape: Exploring signaling pathways in osteoporosis

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 177, P. 116954 - 116954

Published: June 20, 2024

Osteoporosis, characterized by compromised bone density and microarchitecture, represents a significant global health challenge, particularly in aging populations. This comprehensive review delves into the intricate signaling pathways implicated pathogenesis of osteoporosis, providing valuable insights pivotal role signal transduction maintaining homeostasis. The exploration encompasses cellular such as Wnt, Notch, JAK/STAT, NF-κB, TGF-β, all which play crucial roles remodeling. dysregulation these is contributing factor to necessitating profound understanding their complexities unveil molecular mechanisms underlying loss. highlights pathological significance disrupted emphasizing how deviations impact functionality osteoblasts osteoclasts, ultimately resulting heightened resorption formation. A nuanced analysis crosstalk between provided underscore relevance pathophysiology osteoporosis. Furthermore, study addresses some most long non-coding RNAs (lncRNAs) associated with adding an additional layer academic depth immune system involvement various types Finally, we propose that SKP1 can serve potential biomarker

Language: Английский

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Role of oxidative stress in the concurrent development of osteoporosis and tendinopathy: Emerging challenges and prospects for treatment modalities

Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(13)

Published: July 1, 2024

Both osteoporosis and tendinopathy are widely prevalent disorders, encountered in diverse medical contexts. Whilst each condition has distinct pathophysiological characteristics, they share several risk factors underlying causes. Notably, oxidative stress emerges as a crucial intersecting factor, playing pivotal role the onset progression of both diseases. This imbalance arises from dysregulation generating neutralising reactive oxygen species (ROS), leading to an abnormal environment. Elevated levels ROS can induce multiple cellular disruptions, such cytotoxicity, apoptosis activation reduced cell function, contributing tissue deterioration weakening structural integrity bones tendons. Antioxidants substances that prevent or slow down oxidation process, including Vitamin C, melatonin, resveratrol, anthocyanins so on, demonstrating potential treating these overlapping disorders. comprehensive review aims elucidate complex within interlinked pathways comorbid conditions. By integrating contemporary research empirical findings, our objective is outline new conceptual models innovative treatment strategies for effectively managing underscores importance further in-depth validate efficacy antioxidants traditional Chinese medicine plans, well explore targeted interventions focused on promising areas future advancements.

Language: Английский

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Melatonin as a chronobiotic/cytoprotective agent in bone. Doses involved

Journal of Pineal Research, Journal Year: 2023, Volume and Issue: 76(1)

Published: Dec. 11, 2023

Abstract Because the chronobiotic and cytoprotective molecule melatonin diminishes with age, its involvement in postmenopausal senescence pathology has been considered since long. One relevant target site aging individuals is bone where effects mediated by MT1 MT2 receptors are demonstrable. Precursors of cells located marrow exposed to high quantities possibility arises that acts a compound via an autacoid effect. Proteins incorporated into matrix, like procollagen type I c‐peptide, augment after exposure. Melatonin augments osteoprotegerin, osteoblastic protein inhibits differentiation osteoclasts. Osteoclasts for as they degrade partly generating free radicals. Osteoclast activity resorption impaired radical scavenger properties melatonin. The administration doses (less than 10 mg daily) commonly used clinical studies on effect bone. However, human equivalent allometrically derived from animal 1–1.5 mg/kg/day range 75 kg adult, dose rarely clinically. In view absence toxicity phase 1 pharmacological up 100 normal volunteers, further investigation needed determine whether have higher therapeutic efficacy preventing loss.

Language: Английский

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Dual disease co-expression analysis reveals potential roles of estrogen-related genes in postmenopausal osteoporosis and Parkinson’s disease

Frontiers in Genetics, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 7, 2025

The deficiency of estrogen correlates with a range diseases, notably Postmenopausal osteoporosis (PMO) and Parkinson's disease (PD). There is possibility that PMO PD may share underlying molecular mechanisms are pivotal in their development progression. objective this study was to identify critical genes potential associated by examining co-expressed linked PD. Initially, pertinent data concerning were obtained from the GWAS database, followed conducting Bayesian colocalization analysis. Subsequently, dataset (GSE35956) (GSE20164) identified cross-referenced estrogen-related (ERGs). Differentially expressed (DEGs) among PMO, PD, ERGs subjected an array bioinformatics analyses, including Kyoto Encyclopedia Genes Genomes (KEGG) Gene Ontology (GO) enrichment addition protein-protein interaction (PPI) network also involved constructing TF-gene interactions, TF-microRNA coregulatory networks, interactions hub validation through quantitative reverse transcription polymerase chain reaction (qRT-PCR). analysis uncovered shared genetic variants between osteoporosis, posterior probability (PPH4) measured at 0.967. Notably, rs3796661 recognized as variant. A total 11 classified DEGs across ERGs. Five principal KEGG pathways identified, which include p53 signaling pathway, TGF-beta cell cycle, FoxO cellular senescence. Additionally, three genes-WT1, CCNB1, SMAD7-were selected PPI utilizing Cytoscape software. These genes, possess significant diagnostic value for further validated using GEO datasets. Interactions factors well microRNAs established. Ultimately, expression trends confirmed qRT-PCR validation. This anticipated offer innovative approaches identifying biomarkers important therapeutic targets both

Language: Английский

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Melatonin induces RAW264.7 cell apoptosis via the BMAL1/ROS/MAPK-p38 pathway to improve postmenopausal osteoporosis

Bone and Joint Research, Journal Year: 2023, Volume and Issue: 12(11), P. 677 - 690

Published: Nov. 1, 2023

Currently, the effect of drug treatment for osteoporosis is relatively poor, and side effects are numerous serious. Melatonin a potential to improve bone mass in postmenopausal women. Unfortunately, mechanism by which melatonin improves metabolism remains unclear. The aim this study was further investigate osteoporosis.The on mitochondrial apoptosis protein, bmal1 gene, related pathway proteins RAW264.7 (mouse mononuclear macrophage leukaemia cells) were analyzed western blot. Cell Counting Kit-8 used evaluate cell viability. Flow cytometry cells membrane potential. A reactive oxygen species (ROS) detection kit level ROS osteoclast precursors. We bmal1-small interfering RNAs (siRNAs) downregulate Bmal1 gene. established mouse model verified mice via micro-CT. lentiviral activation particles establish an vitro overexpression gene.Melatonin promoted increased expression BMAL1 inhibit phosphorylation mitogen-activated protein kinase (MAPK)-p38. Silencing gene weakened above melatonin. After that, we dehydrocorydaline (DHC) enhance MAPK-p38, reducing levels promoting also blocked. Then, constructed administered results showed that loss ovariectomized mice. Finally, these suggest can regulate activity change MAPK-p38 signalling pathway.Our confirmed promotes through BMAL1/ROS/MAPK-p38, revealed therapeutic osteoporosis. This finding enriches as target pathogenesis

Language: Английский

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Association of dietary carbohydrate and fiber ratio with postmenopausal bone mineral density and prevalence of osteoporosis: A cross-sectional study

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(2), P. e0297332 - e0297332

Published: Feb. 14, 2024

Background This study aimed to investigate the associations of carbohydrate dietary fiber ratio with bone mineral density (BMD) and prevalence osteoporosis in postmenopausal women. Methods cross-sectional retrieved data 2829 women from National Health Nutrition Examination Survey (NHANES) database. Weighted univariable logistic regression models were used correlations carbohydrate, fiber, or osteoporosis. Results Higher intake was correlated decreased odds [odds ratio(OR) = 0.96, 95% confidence interval (CI): 0.93 0.99]. The elevated as increase (OR 1.80, 95%CI: 1.10 2.96). Carbohydrate >17.09 related increased 1.63, 1.04 2.56). Compared ≤11.59 group, associated total femur BMD (β -0.015, -0.028 -0.001) neck -0.020, -0.033 -0.006) -0.001). Conclusion In women, a high carbohydrate/fiber is an risk lower hip less higher BMD.

Language: Английский

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