Current Status of the Diagnosis and Management of Osteoporosis

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(16), P. 9465 - 9465

Published: Aug. 21, 2022

Osteoporosis has been defined as the silent disease of 21st century, becoming a public health risk due to its severity, chronicity and progression affecting mainly postmenopausal women older adults. is characterized by an imbalance between bone resorption production. It diagnosed through different methods such densitometry dual X-rays. The treatment this pathology focuses on aspects. On one hand, pharmacological treatments are use anti-resorptive drugs, well emerging regenerative medicine cell therapies bioactive hydrogels. other non-pharmacological associated with lifestyle habits that should be incorporated, physical activity, diet cessation harmful high consumption alcohol or smoking. This review seeks provide overview theoretical basis in relation biology, existing for diagnosis osteoporosis, including development new strategies.

Language: Английский

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Oxidative Stress and Inflammation in Osteoporosis: Molecular Mechanisms Involved and the Relationship with microRNAs

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(4), P. 3772 - 3772

Published: Feb. 14, 2023

Osteoporosis is characterized by the alteration of bone homeostasis due to an imbalance between osteoclastic resorption and osteoblastic formation. Estrogen deficiency causes loss postmenopausal osteoporosis, pathogenesis which also involves oxidative stress, inflammatory processes, dysregulation expression microRNAs (miRNAs) that control gene at post-transcriptional levels. Oxidative increase in reactive oxygen species (ROS), proinflammatory mediators altered levels miRNAs enhance osteoclastogenesis reduce osteoblastogenesis through mechanisms involving activation MAPK transcription factors. The present review summarizes principal molecular involved role ROS cytokines on osteoporosis. Moreover, it highlights interplay among miRNA levels, state. In fact, ROS, activating transcriptional factors, can affect expression, regulate production processes. Therefore, should help identifying targets for development new therapeutic approaches osteoporotic treatment improve quality life patients.

Language: Английский

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Osteoclasts, Master Sculptors of Bone

Annual Review of Pathology Mechanisms of Disease, Journal Year: 2022, Volume and Issue: 18(1), P. 257 - 281

Published: Oct. 7, 2022

Osteoclasts are multinucleated cells with the unique ability to resorb bone matrix. Excessive production or activation of osteoclasts leads skeletal pathologies that affect a significant portion population. Although therapies effectively target have been developed, they associated sometimes severe side effects, and fuller understanding osteoclast biology may lead more specific treatments. Along those lines, rich body work has defined essential signaling pathways required for formation, function, survival. Nonetheless, recent studies cast new light on long-held views regarding origin these during development homeostasis, their life span, cellular sources factors drive activity homeostasis disease. In this review, we discuss findings in context existing highlight areas ongoing future investigation.

Language: Английский

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Neutrophil elastase: From mechanisms to therapeutic potential

Journal of Pharmaceutical Analysis, Journal Year: 2023, Volume and Issue: 13(4), P. 355 - 366

Published: Jan. 7, 2023

Neutrophil elastase (NE), a major protease in the primary granules of neutrophils, is involved microbicidal activity. NE an important factor promoting inflammation, has bactericidal effects, and shortens inflammatory process. also regulates tumor growth by metastasis microenvironment remodeling. However, plays role killing tumors under certain conditions promotes other diseases such as pulmonary ventilation dysfunction. Additionally, it complex various physiological processes mediates several diseases. Sivelestat, specific inhibitor, strong potential for clinical application, particularly treatment coronavirus disease 2019 (COVID-19). This review discusses pathophysiological associated with applications sivelestat.

Language: Английский

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Targeting strategies for bone diseases: signaling pathways and clinical studies

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: May 17, 2023

Abstract Since the proposal of Paul Ehrlich’s magic bullet concept over 100 years ago, tremendous advances have occurred in targeted therapy. From initial selective antibody, antitoxin to drug delivery that emerged past decades, more precise therapeutic efficacy is realized specific pathological sites clinical diseases. As a highly pyknotic mineralized tissue with lessened blood flow, bone characterized by complex remodeling and homeostatic regulation mechanism, which makes therapy for skeletal diseases challenging than other tissues. Bone-targeted has been considered promising approach handling such drawbacks. With deepening understanding biology, improvements some established bone-targeted drugs novel targets deliveries on horizon. In this review, we provide panoramic summary recent strategies based targeting. We highlight targeting structure biology. For agents, addition classic denosumab, romosozumab, PTH1R ligands, potential process key membrane expressions, cellular crosstalk, gene expression, all cells exploited. delivery, different matrix, marrow, are summarized comparison between ligands. Ultimately, review will summarize translation therapies perspective challenges application clinic future trends area.

Language: Английский

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Acid Neutralization and Immune Regulation by Calcium–Aluminum-Layered Double Hydroxide for Osteoporosis Reversion

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(20), P. 8987 - 8999

Published: May 12, 2022

Osteoporosis is a kind of global chronic bone disease characterized by progressive loss mass and quality reduction, leading to largely increased risk fragility. In clinics, the current treatment osteoporosis relies on inhibition damage osteoclasts but ignores function immune cells in progress osteoporosis, much compromised therapeutic efficacy. this work, highly effective osteoporosis–immunotherapeutic modality established for based acid neutralization synergy with microenvironment regulation specially designed nanocatalytic medicine, calcein functionalized calcium–aluminum-layered double hydroxide (CALC) nanosheets. Briefly, mildly alkaline CALC nanosheets could neutralize acidic accompanying acidity-responsive LDH degradation. Subsequently, calcium phosphate nanoparticles (CAPs) are generated reaction between released Ca2+ from degradation endogenous phosphates, resulting M2 phenotype anti-inflammatory differentiation macrophages through c-Maf transcriptional factor pathway following activity enhancements regulatory T (Treg) deactivation helper 17 (TH17). Both vitro vivo results show an excellent efficacy featuring significant BV/TV (%) enhancement femurs 6.2 10.7, demonstrating high feasibility concept combined regulation. Such inorganic nanomaterial-based strategy provides novel, efficient, biosafe intractable treatment, which will benefit patients suffering osteoporosis.

Language: Английский

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STAT3-mediated osteogenesis and osteoclastogenesis in osteoporosis

Cell Communication and Signaling, Journal Year: 2022, Volume and Issue: 20(1)

Published: July 25, 2022

Abstract Osteoporosis is a common skeletal disease with marked bone loss, deterioration of the microstructure and fragility. An abnormal remodelling cycle relatively increased resorption crucial pathophysiological mechanism. Bone predominantly controlled by osteoblasts osteoclasts, which are specialized cell types that regulated variety osteogenic osteoclastic factors, including cytokines expressed within microenvironment under local or systemic inflammatory conditions. Signal transducer activator transcription 3 (STAT3) plays prominent role in communication between kinases binding downstream gene promotors involved wide range biological pathological processes. Emerging evidence suggests STAT3 its network participate development osteoporosis, this factor may be potent target for osteoporosis treatment. This review focuses on molecular mechanism signalling pathway osteogenesis, osteoclastogenesis particularly bone-related regulate osteoblastic differentiation marrow stromal cells macrophages initiating signalling. also examines cellular interactions among immune cells, haematopoietic osteoblastic/osteoclastic cells.

Language: Английский

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Mechanistic advances in osteoporosis and anti‐osteoporosis therapies

MedComm, Journal Year: 2023, Volume and Issue: 4(3)

Published: May 11, 2023

Osteoporosis is a type of bone loss disease characterized by reduction in mass and microarchitectural deterioration tissue. With the intensification global aging, this now regarded as one major public health problems that often leads to unbearable pain, risk fractures, even death, causing an enormous burden at both human socioeconomic layers. Classic anti-osteoporosis pharmacological options include anti-resorptive anabolic agents, whose ability improve mineral density resist fracture being gradually confirmed. However, long-term or high-frequency use these drugs may bring some side effects adverse reactions. Therefore, increasing number studies are devoted finding new pathogenesis potential therapeutic targets osteoporosis, it great importance comprehensively recognize osteoporosis develop viable efficient approaches. In study, we systematically reviewed literatures clinical evidences mechanistically clinically demonstrate state-of-art advances osteoporosis. This work will endow readers with mechanistical knowledge furthermore present most updated therapies.

Language: Английский

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New mechanistic understanding of osteoclast differentiation and bone resorption mediated by P2X7 receptors and PI3K-Akt-GSK3β signaling

Cellular & Molecular Biology Letters, Journal Year: 2024, Volume and Issue: 29(1)

Published: July 8, 2024

Abstract Objective Osteoporosis is a global health issue characterized by decreased bone mass and microstructural degradation, leading to an increased risk of fractures. This study aims explore the molecular mechanism which P2X7 receptors influence osteoclast formation resorption through PI3K-Akt-GSK3β signaling pathway. Methods An osteoporosis mouse model was generated ovariectomy (OVX) in normal C57BL/6 f/f ; LysM-cre mice. Osteoclasts were isolated for transcriptomic analysis, differentially expressed genes selected functional enrichment analysis. Metabolite analysis performed using liquid chromatography-tandem spectrometry (LC–MS/MS), multivariate statistical pattern recognition used identify differential lipid metabolism markers their distribution. Bioinformatics analyses conducted Encyclopedia Genes Genomes database MetaboAnalyst assess potential biomarkers create metabolic pathway map. Osteoclast precursor cells vitro cell experiments, evaluating viability proliferation Cell Counting Kit 8 (CCK-8) assay. induced differentiate into osteoclasts macrophage colony-stimulating factor (M-CSF) receptor activator nuclear kappa-beta ligand (RANKL), tartrate-resistant acid phosphatase (TRAP) staining compare differentiation morphology, size, quantity between different groups. Western blot expression markers, fusion gene ability osteoclasts. Immunofluorescence employed examine spatial distribution skeletons, protein, nuclei, while pit assay evaluate ability. Finally, vivo animal including micro computed tomography (micro-CT), hematoxylin eosin (HE) staining, TRAP immunohistochemistry, observe tissue differentiation, phosphorylation level Results Transcriptomic metabolomic data collectively reveal that can impact pathogenesis Subsequent experiments showed Sh-P2X7 + Recilisib group exhibited proliferative activity (1.15 versus 0.59), higher absorbance levels (0.68 0.34), significant increase area (13.94 3.50). Expression differentiation-related proteins MMP-9, CK, NFATc1 markedly elevated (MMP-9: 1.72 0.96; CK: 2.54 0.95; NFATc1: 3.05 0.95), along with fluorescent intensity F-actin rings. In contrast, OE-P2X7 LY294002 (0.64 1.29), reduced (0.34 0.82), decrease (5.01 14.96), accompanied weakened 1.14 1.79; 1.26 2.75; 1.17 2.90) intensity. Furthermore, demonstrated compared wild type (WT) Sham group, mice WT OVX significantly CTX NTX serum (CTX: 587.17 129.33; NTX: 386.00 98.83), notable calcium deposition (19.67 53.83), reduction density, trabecular separation, lowered mineral density (BMD). When KO recilisib substantial 503.50 209.83; 339.83 127.00), further (29.67 45.33), as well BMD. Conclusion positively regulate activating

Language: Английский

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Osteoporosis treatment: current drugs and future developments

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: Aug. 12, 2024

Osteoporosis is a common systemic metabolic disease characterized by decrease in bone density and mass, destruction of tissue microstructure, increased fragility leading to fracture susceptibility. Pharmacological treatment osteoporosis the focus current research, anti-osteoporosis drugs usually play role inhibiting resorption, promoting formation, having dual role. However, most have disadvantages single target high toxic side effects. There are many types traditional Chinese medicines (TCM), from wide range sources mostly plants. Herbal plants unique advantages regulating relationship between immune system, acupuncture therapy has significant therapeutic effects combination with medicine for osteoporosis. The cells specific molecular mechanisms TCM preventing treating not been fully elucidated. At present, there lack comprehensive understanding pathological mechanism disease. Therefore, better signaling pathways key molecules involved pathogenesis crucial design targets drug development. In this paper, we review development status currently clinical application under provide relevant basis reference prevention osteoporosis, aim pharmacological research new

Language: Английский

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