Peptide‐Oligonucleotide Nanohybrids Designed for Precise Gene Therapy of Rheumatoid Arthritis

Advanced Materials, Journal Year: 2025, Volume and Issue: unknown

Published: March 19, 2025

Abstract Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by excessive inflammation, pathological bone resorption, and systemic osteoporosis. It lacks effective treatment due to the complex pathogenesis. Gene therapy, especially targeted oligonucleotide (ON) delivery offers new prospect for precise of RA. Nevertheless, clinical application ON therapy still faces various challenges such as rapid enzymolysis RNAse, lack tissue targeting ability, difficulty in cell membrane penetration, incapability endolysosomal escape. To address these issues, novel kind engineered peptide (PON) nanohybrids are designed fabricated, which provide advantages including good biosafety, inflammatory region‐targeted delivery, reactive oxygen species (ROS) scavenging, The PON produce promising effects suppressing responses osteoclastogenesis macrophages via multiple signaling pathways. In vivo administration not only ameliorates local joint destruction osteoporosis state, but also demonstrates prophylactic against progression RA disease. conclusion, study presents strategy broadens biomedical applications gene based on system.

Language: Английский

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Mechanotransducive surfaces for enhanced cell osteogenesis, a review

Biomaterials Advances, Journal Year: 2024, Volume and Issue: 160, P. 213861 - 213861

Published: April 15, 2024

Novel strategies employing mechano-transducing materials eliciting biological outcomes have recently emerged for controlling cellular behaviour. Targeted responses are achieved by manipulating physical, chemical, or biochemical modification of material properties. Advances in techniques such as nanopatterning, chemical modification, molecule embedding, force-tuneable materials, and artificial extracellular matrices helping understand mechanotransduction. Collectively, these manipulate sensing regulate signalling cascades including focal adhesions, YAP-TAZ transcription factors, multiple osteogenic pathways. In this minireview, we providing a summary the influence that particularly titanium-based orthopaedic on cells. We also highlight recent complementary methodological developments including, but not limited to, use metabolomics identification active biomolecules drive differentiation.

Language: Английский

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Lifting the Veil on Myeloma Bone Disease

Published: Jan. 23, 2025

Review Lifting the Veil on Myeloma Bone Disease Rui Chen 1, Liu and Huan 1,2,* 1 Cancer Research Center, School of Medicine, Xiamen University, 361102, China 2 Department Hematology, The First Affiliated Hospital University Institute * Correspondence: [email protected] Received: 13 November 2024; Revised: 29 November; Accepted: January 2025; Published: 23 2025 Abstract: Multiple myeloma (MM), a hematological malignancy originating from malignant plasma cells in bone marrow, predominantly affects elderly, its incidence is rise. It currently second most common malignancy. Osteolytic disease, severe complication detected nearly 80% patients, entire skeletal system, particularly skull, spine, pelvis, long bones limbs. This condition causes pathological fractures, pain, spinal cord compression, hypercalcemia. management damage patients presents numerous challenges, with current clinical treatments primarily relying bisphosphonates anti-RANKL monoclonal antibodies (Denosumab). review summarizes recent advancements research damage, focusing complex interactions between various other cell types that affect skeleton. also discusses challenges encountered research, highlighting potential future directions proposing therapeutic strategies.

Language: Английский

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EZH2 serves as a viable therapeutic target for myeloma-induced osteolytic bone destruction

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 31, 2025

Myelomatous bone disease is a complication characterized by lytic lesions, reduced formation, pain, and increased fracture risk. Understanding these underlying mechanisms crucial for developing effective therapeutic approaches. Here we show the role of enhancer zeste homolog 2 (EZH2) in lesions induced myeloma cells. Our research reveals that cytokines produced myeloma-associated adipocytes activate expression EZH2 Furthermore, find forms transcriptional repression complex with transcription factor AP2α. This promotes trimethylation at lysine 27 histone H3 (H3K27me3) promoter region tumor suppressor gene EMP1, resulting silencing. EMP1 silencing leads to cell proliferation concomitant secretion osteolytic contribute destruction. Importantly, inhibitors effectively treat myeloma-induced lesions. Thus, targeting represents potential strategy preventing managing disease. Osteolytic affects 80% patients multiple myeloma. Here, authors inhibition due activation results cells up-regulation osteoclastogenic promote

Language: Английский

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Biomaterials for Modulating the Immune Microenvironment in Rheumatoid Arthritis

BME Frontiers, Journal Year: 2025, Volume and Issue: 6

Published: Jan. 1, 2025

Rheumatoid arthritis (RA) is a systemic inflammatory autoimmune disease characterized by joint swelling and bone destruction. Despite an incomplete understanding of its genesis, RA tightly linked to the intricate immunological milieu, involving disruptions in molecular signaling imbalance between innate adaptive immune systems. With advancements biomaterials science, role treatment has evolved from mere drug delivery systems therapeutic microenvironment modulators, providing drug-independent strategies for RA. In this review, we will delve into RA, focusing on contributions immunity, damage-associated patterns (DAMPs), cytokines, pathways disease’s pathogenesis inflammation. We provide detailed analysis applications novel nonpharmaceutical treatment, categorized 3 key mechanisms: biofactor pathway regulation, endogenous gas adjustment, cell modulation. The composition, form, principles, efficacy these be explored. thorough discussion topics offer fresh viewpoint guide future research directions.

Language: Английский

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Phospholipase C β4 promotes RANKL-dependent osteoclastogenesis by interacting with MKK3 and p38 MAPK

Experimental & Molecular Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 3, 2025

Phospholipase C β (PLCβ) is involved in diverse biological processes, including inflammatory responses and neurogenesis; however, its role bone cell function largely unknown. Among the PLCβ isoforms (β1-β4), we found that PLCβ4 was most highly upregulated during osteoclastogenesis. Here used global knockout osteoclast lineage-specific conditional (LysM-PLCβ4-/-) mice as subjects demonstrated a crucial regulator of receptor activator nuclear factor κB ligand (RANKL)-induced differentiation. The deletion PLCβ4, both globally lineage, resulted significant reduction formation downregulation marker genes. Notably, male LysM-PLCβ4-/- presented greater mass fewer osteoclasts vivo than their wild-type littermates, without altered osteoblast function. Mechanistically, forms complex with p38 mitogen-activated protein kinase (MAPK) MAPK 3 (MKK3) response to RANKL-induced differentiation, thereby modulating activation. An immunofluorescence assay further confirmed colocalization after RANKL exposure. Moreover, activation rescued impaired restored phosphorylation caused by deficiency. Thus, our findings reveal controls osteoclastogenesis via RANKL-dependent MKK3-p38 pathway may be potential therapeutic candidate for diseases such osteoporosis.

Language: Английский

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Periprosthetic osteolysis: Mechanisms and potential treatment strategies

Cellular Signalling, Journal Year: 2025, Volume and Issue: unknown, P. 111758 - 111758

Published: March 1, 2025

Language: Английский

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RNA interference-mediated osteoprotegerin silencing increases the receptor activator of nuclear factor-kappa B ligand/osteoprotegerin ratio and promotes osteoclastogenesis

World Journal of Stem Cells, Journal Year: 2025, Volume and Issue: 17(4)

Published: April 21, 2025

In vivo degradation of bone scaffolds is significantly influenced by osteoclast (OC) activity, which orchestrated the interplay between receptor activator nuclear factor-kappa B ligand (RANKL) and osteoprotegerin (OPG). The ratio RANKL/OPG a crucial determinant OC-mediated resorption, plays an integral role in remodeling scaffold degradation. Elevated levels RANKL relative to OPG enhance osteoclastogenesis, thereby accelerating process essential for integrating into host tissue. To elucidate effects gene silencing on osteoclastogenesis within rat marrow-derived mesenchymal stem cells (BMSCs). By investigating these effects, study aimed provide deeper insights regulatory mechanisms that influence degradation, potentially leading improved repair regeneration strategies. We employed recombinant lentiviral plasmids silence BMSCs achieve aims. efficacy was assessed using quantitative reverse transcription polymerase chain reaction western blot analysis measure expression RANKL. Tartrate-resistant acid phosphatase staining utilized evaluate formation OCs. Additionally, co-immunoprecipitation assays were conducted explore interactions proteins, further assessing biochemical pathways involved osteoclastogenesis. resulted significant increase ratio, evidenced decreased increased Enhanced observed through tartrate-resistant staining, indicated substantial rise OC response altered balance. provided concrete evidence direct interaction substantiating their pivotal roles regulating activity. findings from this underscore critical axis Silencing effectively increases promoting activity enhancing This mechanism offers promising avenue modulating processes, effective successful integration damaged sites. Future research might focus optimizing control better facilitate tissue engineering regenerative therapies.

Language: Английский

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ST1936 stimulates osteoclastogenesis and suppresses osteoclastic apoptosis through the ERK1/2 signaling pathway in bone marrow–derived macrophages

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 157, P. 114753 - 114753

Published: April 28, 2025

Language: Английский

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Role of oxytocin in bone

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

Published: Sept. 3, 2024

Oxytocin (OT) is a posterior pituitary hormone that, in addition to its role regulating childbirth and lactation, also exerts direct regulatory effects on the skeleton through peripheral OT oxytocin receptor (OTR). Bone marrow mesenchymal stem cells (BMSCs), osteoblasts (OB), osteoclasts (OC), chondrocytes, adipocytes all express OTR. upregulates RUNX2, BMP2, ALP, OCN, thereby enhancing activity of BMSCs promoting their differentiation towards OB rather than adipocytes. directly regulates OPG/RANKL inhibit adipocyte generation, increase expression SOX9 COMP, enhance chondrocyte differentiation. can secrete OT, exerting influence surrounding environment autocrine paracrine mechanisms. increases OC formation NκB/MAP kinase signaling pathway, inhibits osteoclast proliferation by triggering cytoplasmic Ca2+ release nitric oxide synthesis, has dual effect OCs. Under stimulation estrogen, synthesizes amplifying biological estrogen OT. Mediated OT/OTR forms feedforward loop with OB. Apart from interacts arginine vasopressin (AVP), prostaglandins (PGE2), leptin, adiponectin regulate bone metabolism. This review summarizes recent research regulation metabolism OTR, aiming provide insights into clinical applications further research.

Language: Английский

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