Hormone-Related and Drug-Induced Osteoporosis: A Cellular and Molecular Overview

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(6), P. 5814 - 5814

Published: March 18, 2023

Osteoporosis resulting from an imbalance of bone turnover between resorption and formation is a critical health issue worldwide. Estrogen deficiency following nature aging process the leading cause hormone-related osteoporosis for postmenopausal women, while glucocorticoid-induced remains most common in drug-induced osteoporosis. Other medications medical conditions related to secondary include proton pump inhibitors, hypogonadism, selective serotonin receptor chemotherapies, medroxyprogesterone acetate. This review summary cellular molecular mechanisms turnover, pathophysiology osteoporosis, their treatment. Nuclear factor-κβ ligand (RANKL) appears be uncoupling factor that enhances osteoclastogenesis. In contrast, osteoprotegerin (OPG) RANKL antagonist secreted by osteoblast lineage cells. promotes apoptosis osteoclasts inhibits osteoclastogenesis stimulating production OPG reducing osteoclast differentiation after suppression IL-1 TNF, subsequent M-CSF, RANKL, IL-6 release. It can also activate Wnt signaling pathway increase osteogenesis, upregulate BMP promote mesenchymal stem cell pre-osteoblasts osteoblasts rather than adipocytes. leads formation; therefore, greater loss. Excessive glucocorticoids PPAR-2 production, expression Dickkopf-1 (DKK1) osteoblasts, inhibit pathway, thus decreasing differentiation. They survival enhancing inhibiting expression. Appropriate estrogen supplement avoiding excessive glucocorticoid use are deemed primary treatment Additionally, current pharmacological includes bisphosphonates, teriparatide (PTH), inhibitors (such as denosumab). However, many detailed underlying seem complicated unexplored warrant further investigation.

Language: Английский

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Current knowledge of bone-derived factor osteocalcin: its role in the management and treatment of diabetes mellitus, osteoporosis, osteopetrosis and inflammatory joint diseases

Journal of Molecular Medicine, Journal Year: 2024, Volume and Issue: 102(4), P. 435 - 452

Published: Feb. 16, 2024

Abstract Osteocalcin (OC) is the most abundant non-collagenous and osteoblast-secreted protein in bone. It consists of two forms such as carboxylated OC (cOC) undercarboxylated (ucOC). While cOC promotes bone mineralization increases strength, ucOC regarded an endocrinologically active form that may have several functions multiple end organs tissues. Total (tOC) includes both these (cOC ucOC) considered a marker turnover clinical settings. Most data on limited to preclinical studies therefore not accurately reflect situation conditions. For stated reason, aim this review was only summarize current knowledge all characterize its role diabetes mellitus, osteoporosis, osteopetrosis, inflammatory joint diseases, but also provide new interpretations involvement management treatment aforementioned diseases. In context, special emphasis placed available trials. Significantly lower levels tOC could be associated with risk type 2 mellitus. On contrary, level does seem good indicator high status postmenopausal osteoarthritis rheumatoid arthritis. The associations between pharmacological drugs used treat disorders mentioned above been provided. From perspective, serve medium through which certain medications can influence glucose metabolism, body weight, adiponectin secretion, synovial inflammation.

Language: Английский

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Effects of BMSC-Derived EVs on Bone Metabolism

Pharmaceutics, Journal Year: 2022, Volume and Issue: 14(5), P. 1012 - 1012

Published: May 8, 2022

Extracellular vesicles (EVs) are small membrane that can be secreted by most cells. EVs released into the extracellular environment through exocytosis, transporting endogenous cargo (proteins, lipids, RNAs, etc.) to target cells and thereby triggering release of these biomolecules participating in various physiological pathological processes. Among them, derived from bone marrow mesenchymal stem (BMSC-EVs) have similar therapeutic effects BMSCs, including repairing damaged tissues, inhibiting macrophage polarization promoting angiogenesis. In addition, BMSC-EVs, as efficient feasible natural nanocarriers for drug delivery, advantages low immunogenicity, no ethical controversy, good stability easy storage, thus providing a promising strategy many diseases. particular, BMSC-EVs show great potential treatment metabolic This article reviews mechanism formation resorption, which provides new insights future research on strategies

Language: Английский

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Mechanisms of bone remodeling and therapeutic strategies in chronic apical periodontitis

Frontiers in Cellular and Infection Microbiology, Journal Year: 2022, Volume and Issue: 12

Published: July 22, 2022

Chronic periapical periodontitis (CAP) is a typical oral disease in which periodontal inflammation caused by an odontogenic infection eventually leads to bone loss. Uncontrolled infections often lead extensive loss around the root tip, ultimately tooth The main clinical issue treatment of repair jawbone defects, and control first priority. However, cavity open environment, distribution microorganisms through mouth defects inevitable. subversion host cell metabolism initiates disease. presence stimulates series immune responses, turn healing. Given above background, we intended examine paradoxes connections between jaw defect anticipation new ideas for repair. To this end, reviewed microbial factors, human signaling pathways, cells, cytokines involved development CAP, as well concentrated growth factor (CGF) stem cells repair, with aim understanding impact factors on inform etiology management CAP.

Language: Английский

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Advances in the roles of ATF4 in osteoporosis

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 169, P. 115864 - 115864

Published: Nov. 9, 2023

Osteoporosis (OP) is characterized by reduced bone mass, decreased strength, and enhanced fragility fracture risk. Activating transcription factor 4 (ATF4) plays a role in cell differentiation, proliferation, apoptosis, redox balance, amino acid uptake, glycolipid metabolism. ATF4 induces the differentiation of marrow mesenchymal stem cells (BM-MSCs) into osteoblasts, increases osteoblast activity, inhibits osteoclast formation, promoting formation remodeling. In addition, mediates energy metabolism osteoblasts promotes angiogenesis. also involved mediation adipogenesis. can selectively accumulate osteoblasts. directly interact with RUNT-related 2 (RUNX2) up-regulate expression osteocalcin (OCN) osterix (Osx). Several upstream factors, such as Wnt/β-catenin BMP2/Smad signaling pathways, have been ATF4-mediated differentiation. osteoclastogenesis mediating receptor activator nuclear κ-B (NF-κB) ligand (RANKL) signaling. agents, parathyroid (PTH), melatonin, natural compounds, reported to regulate mediate this review, we comprehensively discuss biological activities maintaining homeostasis inhibiting OP development. has become therapeutic target for treatment.

Language: Английский

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The Involvement of microRNAs in Bone Remodeling Signaling Pathways and Their Role in the Development of Osteoporosis

Biology, Journal Year: 2024, Volume and Issue: 13(7), P. 505 - 505

Published: July 7, 2024

Bone remodeling, crucial for maintaining the balance between bone resorption and formation, relies on coordinated activity of osteoclasts osteoblasts. During osteoclastogenesis, hematopoietic stem cells (HSCs) differentiate into osteoclast lineage through signaling pathways OPG/RANK/RANKL. On other hand, during osteoblastogenesis, mesenchymal (MSCs) osteoblast activation TGF-β/BMP/Wnt. Recent studies have shown that remodeling is regulated by post-transcriptional mechanisms including microRNAs (miRNAs). miRNAs are small, single-stranded, noncoding RNAs approximately 22 nucleotides in length. can regulate virtually all cellular processes binding to miRNA-response elements (MRE) at 3’ untranslated region (3′UTR) target mRNA. involved controlling gene expression osteogenic differentiation regulation key cascades formation resorption. Alterations miRNA could favor development disorders, osteoporosis. This review provides a general description their significance osteoporosis development.

Language: Английский

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M2 macrophages-derived exosomes regulate osteoclast differentiation by the CSF2/TNF-α axis

BMC Oral Health, Journal Year: 2024, Volume and Issue: 24(1)

Published: Jan. 18, 2024

Abstract Background Osteoclast-mediated bone resorption cause loss in several diseases. Exosomes have been reported to regulate osteoclast differentiation. M2-polarized macrophages exhibit anti-inflammatory activity. This study aimed explore the effect of exosomes from M2 polarized (M2-exos) on osteoclastogenesis and molecular mechanisms. Methods M2-exos were isolated IL-4-induced Raw264.7 cells (M2 macrophages) used treat osteoclasts (RANKL-induced cells). Osteoclast differentiation was visualized using tartrate resistant acid phosphatase staining. Quantitative real-time PCR (qPCR) conducted measure levels osteoclastogenesis-related genes. The underlying mechanisms evaluated qPCR western blotting. Results suppressed induced by RANKL. Additionally, CSF2 highly expressed macrophages, knockdown further enhanced effects Moreover, positively regulated TNF-α signaling, which inhibition promoted M2-exo-treated osteoclasts. Conclusion inhibited RANKL-induced downregulating expression through inactivating suggesting potential application disease therapy.

Language: Английский

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Unravelling the Complex Relationship between Diet and Nephrolithiasis: The Role of Nutrigenomics and Nutrigenetics

Nutrients, Journal Year: 2022, Volume and Issue: 14(23), P. 4961 - 4961

Published: Nov. 23, 2022

Nephrolithiasis is an increasingly prevalent condition, especially in high income countries, and associated with morbidity. Extraordinary progress genetics made the identification of genetic forms nephrolithiasis possible. These diseases are usually rare do not account for most common that result several factors such as environment, dietary habits, predisposing genes. This knowledge has shaped what we classify nephrolithiasis, a condition now recognized systemic. How to extent all these interact one another end kidney stone formation, growth, recurrence completely understood. Two new research fields have recently been trying give some answers: nutrigenomics nutrigenetics. aim understanding intricate diet/genome interface influences gene expression regulation mainly through epigenetic mechanisms results specific medical conditions cancer, metabolic syndrome, cardiovascular diseases. Epigenetics seems play crucial role could represent link between environmental factors, constantly exposed to, risk nephrolithiasis. In this systematic review, summarize available evidence proven or hypothesized related

Language: Английский

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Roles of Gut Microbiome in Bone Homeostasis and Its Relationship with Bone-Related Diseases

Biology, Journal Year: 2022, Volume and Issue: 11(10), P. 1402 - 1402

Published: Sept. 26, 2022

The extended microbial genome—the gut microbiome (GM)—plays a significant role in host health and disease. It is able to influence number of physiological functions. During dysbiosis, GM associated with the development various chronic diseases impaired bone quality. In general, important for homeostasis can affect it via several mechanisms. This review describes roles through influencing immune endocrine functions, short-chain fatty acids production, calcium absorption gut–brain axis. relationship between composition bone-related diseases, specifically osteoporosis, osteoarthritis, rheumatoid arthritis, diabetes mellitus, obesity cancer, also highlighted summarized. manipulation may become future adjuvant therapy prevention many diseases. Therefore, beneficial effects probiotic improve status individuals aforementioned are provided, but further studies needed clearly confirm its effectiveness. Recent evidence suggests that responsible direct indirect on drug efficacy. Accordingly, alterations interactions related treatment mentioned as well.

Language: Английский

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Human Mesenchymal Stem Cells and Innovative Scaffolds for Bone Tissue Engineering Applications

Tissue Engineering Part B Reviews, Journal Year: 2023, Volume and Issue: 29(5), P. 514 - 531

Published: May 22, 2023

Stem cell-based therapy is a significant topic in regenerative medicine, with predominant role being played by human mesenchymal stem cells (hMSCs). The hMSCs have been shown to be suitable medicine for the treatment of bone tissue. In last few years, average lifespan our population has gradually increased. need biocompatible materials, which exhibit high performances, such as efficiency regeneration, highlighted aging. Current studies emphasize benefit using biomimetic biomaterials, also known scaffolds, grafts speed up repair at fracture site. For healing injured and techniques utilizing combination these together bioactive substances, drawn great interest. Cell therapy, based on use hMSCs, alongside materials damaged bone, obtained promising results. this work, several aspects cell biology, tissue engineering, biomaterials applied healing/regrowth will considered. addition, fields recent progress clinical applications are discussed. restoration large defects both challenging issue socioeconomic problem global scale. Different therapeutic approaches proposed (hMSCs), considering their paracrine effect potential differentiation into osteoblasts. However, different limitations still overcome opportunity repair, including hMSC administration methods. To identify delivery system, new strategies innovative biomaterials. This review provides an update literature hMSC/scaffold management fractures.

Language: Английский

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