Stem cell–homing hydrogel-based miR-29b-5p delivery promotes cartilage regeneration by suppressing senescence in an osteoarthritis rat model

Science Advances, Journal Year: 2022, Volume and Issue: 8(13)

Published: March 30, 2022

Osteoarthritis (OA) is a common joint disease characterized by progressive loss of cartilage and reduction in lubricating synovial fluid, which lacks effective treatments currently. Here, we propose hydrogel-based miRNA delivery strategy to rejuvenate impaired creating regenerative microenvironment mitigate chondrocyte senescence that mainly contributes breakdown during OA development. An aging-related miRNA, miR-29b-5p, was first found be markedly down-regulated cartilage, their up-regulation suppressed the expression matrix metalloproteinases senescence-associated genes (P16INK4a/P21) via ten-eleven-translocation enzyme 1 (TET1). injectable bioactive self-assembling peptide nanofiber hydrogel applied deliver agomir-29b-5p, functionalized conjugating stem cell-homing SKPPGTSS for endogenous cell recruitment simultaneously. Sustained miR-29b-5p cells subsequent differentiation into chondrocytes led successful repair rejuvenation. This enables miRNA-based therapeutic modality become viable alternative surgery treatment.

Language: Английский

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Cartilage Homeostasis and Osteoarthritis

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(11), P. 6316 - 6316

Published: June 5, 2022

Healthy limb joints are important for maintaining health and attaining longevity. Endochondral ossification (the replacement of cartilage with bone, occurring during skeletal development) is essential bone formation, especially in long-axis bones. In contrast to endochondral ossification, chondrocyte populations articular persist maintain joint tissue into adulthood. Articular cartilage, a connective consisting chondrocytes their surrounding extracellular matrices, plays an role the mechanical cushioning postnatal locomotion. Osteoarthritis (OA) pathology relates disruptions balance between anabolic catabolic signals, that is, loss homeostasis due aging or overuse cartilages. The onset OA increases age, shortening person’s healthy life expectancy. Although many people experience pain, mainstay treatment symptomatic therapy, no fundamental has yet been established. To establish regenerative preventative therapies diseases, further understanding mechanisms development, morphosis, required. this review, we describe general development pathology, followed by discussion on signals homeostasis, mainly microRNAs.

Language: Английский

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Adhesive hydrogels in osteoarthritis: from design to application

Military Medical Research, Journal Year: 2023, Volume and Issue: 10(1)

Published: Jan. 30, 2023

Osteoarthritis (OA) is the most common type of degenerative joint disease which affects 7% global population and more than 500 million people worldwide. One research frontier development hydrogels for OA treatment, operate either as functional scaffolds tissue engineering or delivery vehicles additives. Both approaches address big challenge: establishing stable integration such systems implants. Adhesive provide possible solutions to this challenge. However, few studies have described current advances in using adhesive hydrogel treatment. This review summarizes commonly used with their adhesion mechanisms components. Additionally, recognizing that a complex involving different biological mechanisms, bioactive therapeutic strategies are also presented. By presenting an interdisciplinary way, including both fields chemistry biology, will attempt comprehensive insight designing novel bioadhesive therapy.

Language: Английский

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Three‐dimensional bioprinting biphasic multicellular living scaffold facilitates osteochondral defect regeneration

Interdisciplinary materials, Journal Year: 2024, Volume and Issue: 3(5), P. 738 - 756

Published: June 2, 2024

Abstract Due to tissue lineage variances and the anisotropic physiological characteristics, regenerating complex osteochondral tissues (cartilage subchondral bone) remains a great challenge, which is primarily due distinct requirements for cartilage bone regeneration. For regeneration, significant amount of newly generated chondrocytes required while maintaining their phenotype. Conversely, regeneration necessitates inducing stem cells differentiate into osteoblasts. Additionally, construction interface crucial. In this study, we fabricated biphasic multicellular bioprinted scaffold mimicking natural employing three‐dimensional (3D) bioprinting technology. Briefly, gelatin‐methacryloyl (GelMA) loaded with articular marrow mesenchymal (ACs/BMSCs), serving as layer, preserved phenotype ACs promoted differentiation BMSCs through interaction between BMSCs, thereby facilitating GelMA/strontium‐substituted xonotlite (Sr‐CSH) regulated osteoblasts enhanced secretion matrix by in layer slow release bioactive ions from Sr‐CSH. GelMA, material, contributed reconstruction interface. Ultimately, demonstrated satisfactory simultaneous defects. promising strategy application 3D technology was proposed.

Language: Английский

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Single-Cell RNA-Seq Reveals Transcriptomic Heterogeneity and Post-Traumatic Osteoarthritis-Associated Early Molecular Changes in Mouse Articular Chondrocytes

Cells, Journal Year: 2021, Volume and Issue: 10(6), P. 1462 - 1462

Published: June 10, 2021

Articular cartilage is a connective tissue lining the surfaces of synovial joints. When severely wears down, it leads to osteoarthritis (OA), debilitating disease that affects millions people globally. The articular composed dense extracellular matrix (ECM) with sparse distribution chondrocytes varying morphology and potentially different functions. Elucidating molecular functional profiles various chondrocyte subtypes understanding interplay between these other cell types in joint will greatly expand our biology OA pathology. Although recent advances high-throughput OMICS technologies have enabled molecular-level characterization tissues organs at an unprecedented resolution, thorough profiling has not yet been undertaken, which may be part due technical difficulties isolating from ECM. In this study, we profiled healthy injured mouse knee joints single-cell resolution identified nine distinct injury-induced early changes chondrocytes. We also compared subpopulations human evaluated extent similarity mice humans. This work expands view heterogeneity rapid populations response trauma highlights potential mechanisms trigger degeneration.

Language: Английский

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The hypertrophic chondrocyte: To be or not to be.

PubMed, Journal Year: 2021, Volume and Issue: 36(10), P. 1021 - 1036

Published: Oct. 1, 2021

Hypertrophic chondrocytes are the master regulators of endochondral ossification; however, their ultimate cell fates cells remain largely elusive due to transient nature. Historically, hypertrophic have been considered as terminal state growth plate chondrocytes, which destined meet inevitable demise at primary spongiosa. Chondrocyte hypertrophy is accompanied by increased organelle synthesis and rapid intracellular water uptake, serve major drivers longitudinal bone growth. This process delicately regulated signaling pathways target genes, including hormone (GH), insulin factor-1 (IGF-1), indian hedgehog (Ihh), parathyroid hormone-related protein (PTHrP), morphogenetic proteins (BMPs), sex determining region Y-box 9 (Sox9), runt-related transcription factors (Runx) fibroblast factor receptors (FGFRs). orchestrate ossification regulating osteogenic-angiogenic osteogenic-osteoclastic coupling through production vascular endothelial (VEGF), receptor activator nuclear kappa-B ligand (RANKL) matrix metallopeptidases-9/13 (MMP-9/13). also indirectly regulate resorption cartilaginous extracellular matrix, controlling formation a special subtype osteoclasts termed "chondroclasts". Notably, may possess innate potential for plasticity, reentering cycle differentiating into osteoblasts other types mesenchymal in marrow space. We be able harness this unique plasticity therapeutic purposes, variety skeletal abnormalities injuries. In review, we discuss morphological molecular properties carry out important functions during regeneration.

Language: Английский

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Interleukin-6 signaling mediates cartilage degradation and pain in posttraumatic osteoarthritis in a sex-specific manner

Science Signaling, Journal Year: 2022, Volume and Issue: 15(744)

Published: July 26, 2022

Osteoarthritis (OA) and posttraumatic OA (PTOA) are caused by an imbalance in catabolic anabolic processes articular cartilage proinflammatory changes throughout the joint, leading to joint degeneration pain. We examined whether interleukin-6 (IL-6) signaling contributed degradation pain PTOA. Genetic ablation of Il6 male mice decreased PTOA-associated catabolism, innervation knee nociceptive without improving subchondral bone sclerosis or chondrocyte apoptosis. These effects were not observed female Il6-/- mice. Compared with wild-type mice, activation IL-6 downstream mediators STAT3 ERK was reduced knees dorsal root ganglia (DRG) after injury. Janus kinases (JAKs) critical for STAT catabolism DRG tissue explants. Whereas important mediated neurite outgrowth neurons. data demonstrate that mediates both associated PTOA a sex-specific manner identify tissue-specific contributions effectors signaling, which potential therapeutic targets disease-modifying drugs.

Language: Английский

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Thermosensitive Hydrogel Loaded with Primary Chondrocyte-Derived Exosomes Promotes Cartilage Repair by Regulating Macrophage Polarization in Osteoarthritis

Tissue Engineering and Regenerative Medicine, Journal Year: 2022, Volume and Issue: 19(3), P. 629 - 642

Published: April 18, 2022

Language: Английский

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Hypertrophic chondrocytes serve as a reservoir for marrow-associated skeletal stem and progenitor cells, osteoblasts, and adipocytes during skeletal development

eLife, Journal Year: 2022, Volume and Issue: 11

Published: Feb. 18, 2022

Hypertrophic chondrocytes give rise to osteoblasts during skeletal development; however, the process by which these non-mitotic cells make this transition is not well understood. Prior studies have also suggested that stem and progenitor (SSPCs) localize surrounding periosteum serve as a major source of marrow-associated SSPCs, osteoblasts, osteocytes, adipocytes development. To further understand cell hypertrophic contribute or other marrow associated cells, we utilized inducible constitutive chondrocyte lineage tracing reporter mouse models (

Language: Английский

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Cartilage Lacuna‐Inspired Microcarriers Drive Hyaline Neocartilage Regeneration

Advanced Materials, Journal Year: 2023, Volume and Issue: 35(30)

Published: March 6, 2023

Abstract Cartilage equivalents from hydrogels containing chondrocytes exhibit excellent potential in hyaline cartilage regeneration, yet current approaches have limited success at reconstituting the architecture to culture nondifferentiated vitro. In this study, specially designed lacunar hyaluronic acid microcarriers (LHAMCs) with mechanotransductive conditions that rapidly form stable (HA) N ‐hydroxy succinimide ester (NHS‐ester) are reported. Specifically, carboxyl‐functionalized HA is linked collagen type I via amide‐crosslinking, and gas foaming produced by ammonium bicarbonate forms concave surface of microcarriers. The temporal 3D on LHAMCs uniquely remodels extracellular matrix induce cartilaginous microtissue regeneration prevents an anaerobic‐to‐aerobic metabolism transition response geometric constraints. Furthermore, inhibiting canonical Wnt pathway, prevent β ‐catenin translocation nucleus, repressing chondrocyte dedifferentiation. Additionally, subcutaneous implantation model indicates display favorable cytocompatibility drive robust chondrocyte‐derived neocartilage formation. These findings reveal a novel strategy for regulating study paves way better understanding geometrical insight clues into mechanotransduction interaction cell fate, opening new avenues advancing tissue engineering.

Language: Английский

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