Inflammation and Bone Metabolism in Rheumatoid Arthritis: Molecular Mechanisms of Joint Destruction and Pharmacological Treatments

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(5), P. 2871 - 2871

Published: March 6, 2022

Rheumatoid arthritis (RA) is an inflammatory disease characterized by a variety of symptoms and pathologies often presenting with polyarthritis. The primary symptom in the initial stage joint swelling due to synovitis. With progression, cartilage bone are affected cause deformities. Advanced osteoarticular destruction deformation can irreversible physical disabilities. Physical disabilities not only deteriorate patients’ quality life but also have substantial medical economic effects on society. Therefore, prevention progression important task. Recent studies progressively improved our understanding molecular mechanism which synovitis caused immune disorders results activation osteoclasts; activated osteoclasts turn para-articular osteoporosis. In this paper, we review mechanisms metabolism under physiological RA conditions, describe therapeutic intervention against bone.

Language: Английский

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SIRT2 regulates extracellular vesicle-mediated liver–bone communication

Nature Metabolism, Journal Year: 2023, Volume and Issue: 5(5), P. 821 - 841

Published: May 15, 2023

Abstract The interplay between liver and bone metabolism remains largely uncharacterized. Here, we uncover a mechanism of liver-bone crosstalk regulated by hepatocyte SIRT2. We demonstrate that SIRT2 expression is increased in aged mice elderly humans. Liver-specific deficiency inhibits osteoclastogenesis alleviates loss mouse models osteoporosis. identify leucine-rich α-2-glycoprotein 1 (LRG1) as functional cargo hepatocyte-derived small extracellular vesicles (sEVs). In SIRT2-deficient hepatocytes, LRG1 levels sEVs are upregulated, leading to transfer bone-marrow-derived monocytes (BMDMs), turn, inhibition osteoclast differentiation via reduced nuclear translocation NF-κB p65. Treatment with carrying high human BMDMs osteoporosis, resulting attenuated mice. Furthermore, the plasma level positively correlated mineral density Thus, drugs targeting hepatocyte-osteoclast communication may constitute promising therapeutic strategy for primary

Language: Английский

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Biocompatibility pathways and mechanisms for bioactive materials: The bioactivity zone

Bioactive Materials, Journal Year: 2021, Volume and Issue: 10, P. 306 - 322

Published: Aug. 26, 2021

This essay analyzes the scientific evidence that forms basis of bioactive materials, covering fundamental understanding bioactivity phenomena and correlation with mechanisms biocompatibility biomaterials. is a detailed assessment performance in areas such as bone-induction, cell adhesion, immunomodulation, thrombogenicity antimicrobial behavior. Bioactivity modulation biological activity by characteristics interfacial region incorporates material surface immediate local host tissue. Although term 'bioactive material' widely used has well understood general meaning, it would be useful now to concentrate on this region, considered 'the zone'. are either due topographical/micromechanical characteristics, or biologically active species presented zone. Examples effects osteoblast - osteoclast balance, nanotopographical regulation bactericidal nanostructures. Regulation include their influence, especially metal ions, signaling pathways bone formation, role adhesion molecules peptides attachment, macrophage polarization immunoregulatory peptides. While much experimental data exists demonstrate potential phenomena, there considerable barriers effective clinical translation. shows solid existence associated some types biomaterials, when modified manner designed specifically induce activity.

Language: Английский

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Insights into oxidative stress in bone tissue and novel challenges for biomaterials

Materials Science and Engineering C, Journal Year: 2021, Volume and Issue: 130, P. 112433 - 112433

Published: Sept. 16, 2021

Language: Английский

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Bone Scaffolds: An Incorporation of Biomaterials, Cells, and Biofactors

ACS Biomaterials Science & Engineering, Journal Year: 2021, Volume and Issue: 7(12), P. 5397 - 5431

Published: Nov. 19, 2021

Large injuries to bones are still one of the most challenging musculoskeletal problems. Tissue engineering can combine stem cells, scaffold biomaterials, and biofactors aid in resolving this complication. Therefore, review aims provide information on recent advances made utilize potential biomaterials for making bone scaffolds assisted cell therapy use tissue engineering. The requirements different types used reviewed. Furthermore, importance cells (growth factors extracellular vesicles) regeneration their key findings discussed. Lastly, some main obstacles future trends highlighted.

Language: Английский

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Topography-mediated immunomodulation in osseointegration; Ally or Enemy

Biomaterials, Journal Year: 2022, Volume and Issue: 291, P. 121903 - 121903

Published: Nov. 9, 2022

Language: Английский

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Breast Cancer with Bone Metastasis: Molecular Insights and Clinical Management

Cells, Journal Year: 2021, Volume and Issue: 10(6), P. 1377 - 1377

Published: June 2, 2021

Despite the remarkable advances in diagnosis and treatment of breast cancer patients, presence or development metastasis remains an incurable condition. Bone is one most frequent sites distant dissemination negatively impacts on patient’s survival overall frailty. The interplay between tumor cells bone microenvironment induces destruction progression. To date, clinical management metastatic encompasses anti-tumor systemic therapies along with bone-targeting agents, aimed at slowing resorption to reduce risk skeletal-related events. However, their effect patients’ controversial. Unraveling biology that governs neoplastic tissue would provide means for new therapeutic agents. This article outlines state-of-the art characterization targeting cancer, focusing major translational studies this clinically relevant topic.

Language: Английский

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Impact of the host response and osteoblast lineage cells on periodontal disease

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Oct. 11, 2022

Periodontitis involves the loss of connective tissue attachment and alveolar bone. Single cell RNA-seq experiments have provided new insight into how resident cells infiltrating immune function in response to bacterial challenge periodontal tissues. Periodontal disease is induced by a combined innate adaptive dysbiosis that initiated including epithelial fibroblasts, which recruit cells. Chemokines cytokines stimulate recruitment osteoclast precursors osteoclastogenesis TNF, IL-1β, IL-6, IL-17, RANKL other factors. Inflammation also suppresses coupled bone formation limit repair osteolytic lesions. Bone lining cells, osteocytes ligament play key role both processes. The contains exhibit similarities tendon osteoblast-lineage mesenchymal stem consisting osteoprogenitors osteoblasts are influenced through MCSF RANKL, directly induce osteoclastogenesis. Following resorption, factors released from resorbed matrix osteoclasts osteal macrophages osteoblast surface. Osteoblast differentiation regulated multiple signaling pathways Wnt, Notch, FGF, IGF-1, BMP, Hedgehog pathways. Diabetes, cigarette smoking aging enhance pathologic processes increase resorption inhibit accelerate loss. Other pathologies such as rheumatoid arthritis, post-menopausal osteoporosis unloading/disuse affect lineage participate lesions promoting inhibiting formation. Thus, periodontitis activation an inflammatory large number osseous

Language: Английский

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The Role Of BMPs in the Regulation of Osteoclasts Resorption and Bone Remodeling: From Experimental Models to Clinical Applications

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: April 26, 2022

In response to mechanical forces and the aging process, bone in adult skeleton is continuously remodeled by a process which old damaged removed bone-resorbing osteoclasts subsequently replaced new bone-forming cells, osteoblasts. During this essential of remodeling, osteoclastic resorption tightly coupled osteoblastic formation. Bone-resorbing multinuclear giant osteoclasts, derive from monocyte/macrophage hematopoietic lineage their differentiation driven distinct signaling molecules transcription factors. Critical factors for are Macrophage Colony Stimulating Factor (M-CSF) Receptor Activator Nuclear Factor-κB Ligand (RANKL). Besides activity, secrete coupling promote recruitment osteoblast precursors surface, regulating thus whole remodeling. Bone morphogenetic proteins (BMPs), family multi-functional growth involved numerous molecular pathways, have significant role osteoblast-osteoclast communication significantly impact It well known that BMPs help maintain healthy stimulating mineralization, survival. Recently, increasing evidence indicates not only anabolic part remodeling but also influence catabolism. The deletion BMP receptor type 1A (BMPRIA) increased formation, suggesting BMPR1A regulates osteoblasts reducing bone-formation activity during dual effect on mineralization highlights homeostasis they appear be pathological processes inflammatory disorders affecting bones joints. Certain (BMP2 -7) were approved clinical use; however, rather than formation observed applications, osteoclast activation subsequent osteolysis. Here, we summarize current knowledge its resorption, osteoblast–osteoclast coupling. Furthermore, discussion application recombinant therapy based recent preclinical studies.

Language: Английский

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Osteometabolism: Metabolic Alterations in Bone Pathologies

Cells, Journal Year: 2022, Volume and Issue: 11(23), P. 3943 - 3943

Published: Dec. 6, 2022

Renewing interest in the study of intermediate metabolism and cellular bioenergetics is brought on by global increase prevalence metabolic illnesses. Understanding mechanisms that integrate energy entire organism has significantly improved with application contemporary biochemical tools for quantifying fuel substrate cutting-edge mouse genetic procedures. Several unexpected findings genetically altered mice have prompted research into direction skeletal cells. These point to possibility novel endocrine connections through which bone cells can convey their status other control centers. expanded function skeleton system turn inspired new lines aimed at characterizing needs bioenergetic characteristics these Bone-forming osteoblast bone-resorbing osteoclast require a constant large supply substrates such as glucose, fatty acids, glutamine, etc., differentiation functional activity. According latest research, important developmental signaling pathways are connected programs, may accommodate variations requirements during life cycle. The present review article provides unique perspective past along governing utilization bioenergetics. In addition, we discussed therapeutic inventions currently being utilized treatment management bone-related diseases osteoporosis, rheumatoid arthritis (RA), osteogenesis imperfecta (OIM), modulating energetics We further emphasized role GUT-associated metabolites (GAMs) short-chain acids (SCFAs), medium-chain (MCFAs), indole derivates, bile regulating plausible maintaining health. Emphasis importantly placed highlighting knowledge gaps this field biology, i.e., "Osteometabolism" (proposed our group) need be explored characterize physiological importance cell context human health related diseases.

Language: Английский

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