Hypoxic Conditions Modulate Chondrogenesis through the Circadian Clock: The Role of Hypoxia-Inducible Factor-1α DOI Creative Commons

Krisztián Z. Juhász,

Tibor Hajdú, Patrik Kovács

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(6), P. 512 - 512

Published: March 14, 2024

Hypoxia-inducible factor-1 (HIF-1) is a heterodimer transcription factor composed of an alpha and beta subunit. HIF-1α master regulator cellular response to hypoxia by activating the genes that facilitate metabolic adaptation hypoxia. Since chondrocytes in mature articular cartilage reside hypoxic environment, plays important role chondrogenesis physiological lifecycle cartilage. Accumulating evidence suggests interactions between HIF pathways circadian clock. The clock emerging both developing chondrocytes. However, how rhythm established during early steps formation through what signaling it promotes healthy chondrocyte phenotype still not entirely known. This narrative review aims deliver concise analysis existing understanding dynamic interplay molecular chondrocytes, states health disease, while also incorporating creative interpretations. We explore diverse hypotheses regarding intricate among these propose relevant therapeutic strategies for disorders such as osteoarthritis.

Language: Английский

Articular cartilage repair biomaterials: strategies and applications DOI Creative Commons
Mingkai Wang, Yan Wu, Guangfeng Li

et al.

Materials Today Bio, Journal Year: 2024, Volume and Issue: 24, P. 100948 - 100948

Published: Jan. 5, 2024

Articular cartilage injury is a frequent worldwide disease, while effective treatment urgently needed. Due to lack of blood vessels and nerves, the ability self-repair limited. Despite availability various clinical treatments, unfavorable prognoses complications remain prevalent. However, advent tissue engineering regenerative medicine has generated considerable interests in using biomaterials for articular repair. Nevertheless, there remains notable scarcity comprehensive reviews that provide an in-depth exploration strategies applications. Herein, we present overview primary bioactive substances from perspective repair cartilage. The include regeneration, substitution, immunization. We comprehensively delineate influence mechanically supportive scaffolds on cellular behavior, shedding light emerging scaffold technologies, including stimuli-responsive smart scaffolds, 3D-printed bionic scaffolds. Biologically active substances, factors, stem cells, extracellular vesicles (EVs), organoids, are elucidated their roles regulating activity chondrocytes. Furthermore, composite produced industrially put into use, also explicitly presented. This review offers innovative solutions treating ailments emphasizes potential translation.

Language: Английский

Citations

58
Injectable Microgels with Hybrid Exosomes of Chondrocyte‐Targeted FGF18 Gene‐Editing and Self‐Renewable Lubrication for Osteoarthritis Therapy DOI

Manyu Chen,

Yan Lu, Yuhan Liu

et al.

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(16)

Published: Jan. 24, 2024

Abstract Abnormal silencing of fibroblast growth factor (FGF) signaling significantly contributes to joint dysplasia and osteoarthritis (OA); However, the clinical translation FGF18‐based protein drugs is hindered by their short half‐life, low delivery efficiency need for repeated articular injections. This study proposes a CRISPR/Cas9‐based approach effectively activate FGF18 gene OA chondrocytes at genome level in vivo, using chondrocyte‐affinity peptide (CAP) incorporated hybrid exosomes (CAP/FGF18‐hyEXO) loaded with an FGF18‐targeted gene‐editing tool. Furthermore, CAP/FGF18‐hyEXO are encapsulated methacrylic anhydride‐modified hyaluronic (HAMA) hydrogel microspheres via microfluidics photopolymerization create injectable microgel system (CAP/FGF18‐hyEXO@HMs) self‐renewable hydration layers provide persistent lubrication response frictional wear. Together, CAP/FGF18‐hyEXO@HMs, combined vivo editing continuous lubrication, have demonstrated capacity synergistically promote cartilage regeneration, decrease inflammation, prevent ECM degradation both vitro holding great potential translation.

Language: Английский

Citations

48
NIR-enhanced Pt single atom/g-C3N4 nanozymes as SOD/CAT mimics to rescue ATP energy crisis by regulating oxidative phosphorylation pathway for delaying osteoarthritis progression DOI Creative Commons

Jianhui Xiang,

Xin Yang,

Manli Tan

et al.

Bioactive Materials, Journal Year: 2024, Volume and Issue: 36, P. 1 - 13

Published: Feb. 21, 2024

Osteoarthritis (OA) progresses due to the excessive generation of reactive oxygen and nitrogen species (ROS/RNS) abnormal ATP energy metabolism related oxidative phosphorylation pathway in mitochondria. Highly active single-atom nanozymes (SAzymes) can help regulate redox balance have shown their potential treatment inflammatory diseases. In this study, we innovatively utilised ligand-mediated strategies chelate Pt

Language: Английский

Citations

29
Electroactive Biomaterials Regulate the Electrophysiological Microenvironment to Promote Bone and Cartilage Tissue Regeneration DOI
Li Chen,

Jianye Yang,

Zhengwei Cai

et al.

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: 34(23)

Published: Jan. 7, 2024

Abstract The incidence of large bone and articular cartilage defects caused by traumatic injury is increasing worldwide; the tissue regeneration process for these injuries lengthy due to limited self‐healing ability. Endogenous bioelectrical phenomenon has been well recognized play an important role in homeostasis regeneration. Studies have reported that electrical stimulation (ES) can effectively regulate various biological processes holds promise as external intervention enhance synthesis extracellular matrix, thereby accelerating Hence, electroactive biomaterials considered a biomimetic approach ensure functional recovery integrating physiological signals, including electrical, biochemical, mechanical signals. This review will discuss endogenous bioelectricity tissue, effects ES on cellular behaviors. Then, recent advances materials their applications are systematically overviewed, with focus advantages disadvantages repair performances modulation cell fate. Finally, significance mimicking electrophysiological microenvironment target emphasized future development challenges strategies proposed.

Language: Английский

Citations

24
Recent advancements in cartilage tissue engineering innovation and translation DOI
Rachel C. Nordberg, Benjamin J. Bielajew, Takumi Takahashi

et al.

Nature Reviews Rheumatology, Journal Year: 2024, Volume and Issue: 20(6), P. 323 - 346

Published: May 13, 2024

Language: Английский

Citations

23
Bifunctional TRPV1 Targeted Magnetothermal Switch to Attenuate Osteoarthritis Progression DOI Creative Commons

Zhongyang Lv,

Peng Wang, Weitong Li

et al.

Research, Journal Year: 2024, Volume and Issue: 7

Published: Jan. 1, 2024

Transient receptor potential vanilloid family member 1 (TRPV1) has been revealed as a therapeutic target of osteoarthritis (OA), the most common deteriorating whole joint disease, by impeding macrophagic inflammation and chondrocytes ferroptosis. However, clinical application for capsaicin TRPV1 agonist is largely limited its chronic toxicity. To address this issue, we developed bifunctional controllable magnetothermal switch targeting alleviation OA progression coupling magnetic nanoparticles (MNPs) to monoclonal antibodies (MNPs-TRPV1). Under alternating field (AMF) stimulation, MNPs-TRPV1 locally dissipated heat, which was sufficient trigger opening activation TRPV1, effectively impeded chondrocyte This modulation simultaneously attenuated synovitis cartilage degeneration in mice incurred destabilization medial meniscus surgery, indicating delayed progression. Furthermore, with AMF exposure remarkably reduced knee pain sensitivity, alleviated crippled gait, improved spontaneous ambulatory activity performance model. Overall, work provides pathogenesis-based precise therapy temporally spatially manner.

Language: Английский

Citations

18
Clinical-grade extracellular vesicles derived from umbilical cord mesenchymal stromal cells: preclinical development and first-in-human intra-articular validation as therapeutics for knee osteoarthritis DOI Creative Commons
Aliosha I. Figueroa‐Valdés, Patricia Luz‐Crawford, Yeimi Herrera-Luna

et al.

Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 13, 2025

Osteoarthritis (OA) is a joint disease characterized by articular cartilage degradation. Persistent low-grade inflammation defines OA pathogenesis, with crucial involvement of pro-inflammatory M1-like macrophages. While mesenchymal stromal cells (MSC) and their small extracellular vesicles (sEV) hold promise for treatment, achieving consistent clinical-grade sEV products remains significant challenge. This study aims to develop fully characterized, reproducible, batches derived from umbilical cord (UC)-MSC the treatment while assessing its efficacy safety. Initially, standardized, research-grade manufacturing protocol was established ensure production. UC-MSC-sEV characterization under non-cGMP conditions showed miRNA protein profiles, suggesting potential standardized manufacturing. In vitro studies evaluated efficacy, safety, potency sEV; animal confirmed effectiveness vitro, polarized macrophages an anti-inflammatory M2b-like phenotype, through STAT1 modulation, indicating create environment in affected joints. silico sEV's immunosuppressive signature proteome analysis. mouse model, injected intra-articularly (IA) induced hyaline regeneration, validated histological μCT analyses. The unique detection signals within knee over time highlights safety profile confirming retention joint. product development involved refining, standardizing, validating processes compliance GMP standards. initial assessment via IA administration first-in-human no adverse effects after 12 month follow-up period. These results support progress this sEV-based therapy early-phase clinical trial, details which are presented discussed work. provides data on using as local OA, highlighting regenerative properties preclinical proof-of-principle application.

Language: Английский

Citations

4
Harnessing the potential of hyaluronic acid methacrylate (HAMA) hydrogel for clinical applications in orthopaedic diseases DOI Creative Commons
Junliang Lu, Zongzhan Gao, Wei He

et al.

Journal of Orthopaedic Translation, Journal Year: 2025, Volume and Issue: 50, P. 111 - 128

Published: Jan. 1, 2025

The treatment of orthopaedic diseases, such as fractures and osteoarthritis, remains a significant challenge due to the complex requirements for mechanical strength tissue repair. Hydrogels based on hyaluronic acid methacrylate (HAMA) show promise engineering materials these conditions. Hyaluronic (HA) is natural component extracellular matrix, known its good compatibility. HAMA-based hydrogels can be adjusted through crosslinking by combining them with other materials. This review provides an overview recent research applications in diseases. First, we summarize techniques preparation characterization HAMA hydrogels. Next, offer detailed use treating conditions cartilage injuries, bone defects, meniscus injuries. Additionally, discuss diseases related orthopaedics. Finally, point out challenges propose future directions clinical translation strong translational potential orthopaedics their biocompatibility, adjustable properties, regenerative capabilities. With ongoing research, are well-positioned applications, particularly repair, osteoarthritis treatment.

Language: Английский

Citations

3
Understanding interleukin 11 as a disease gene and therapeutic target DOI Creative Commons
Stuart A. Cook

Biochemical Journal, Journal Year: 2023, Volume and Issue: 480(23), P. 1987 - 2008

Published: Dec. 6, 2023

Interleukin 11 (IL11) is an elusive member of the IL6 family cytokines. While initially thought to be a haematopoietic and cytoprotective factor, more recent data show instead that IL11 redundant for haematopoiesis toxic. In this review, reasons led original misunderstandings biology, which are now understandable, explained with particular attention on use recombinant human in mice humans. Following tissue injury, as part evolutionary ancient homeostatic response, secreted from damaged mammalian cells signal via JAK/STAT3, ERK/P90RSK, LKB1/mTOR GSK3β/SNAI1 autocrine paracrine. This activates program mesenchymal transition epithelial, stromal, endothelial cause inflammation, fibrosis, stalled endogenous repair, leading organ failure. The role signalling cell- organ-specific pathobiology described, large unknowns about biology discussed promise targeting therapeutic approach reviewed.

Language: Английский

Citations

26
Harnessing Nanomedicine for Cartilage Repair: Design Considerations and Recent Advances in Biomaterials DOI
Huiqun Zhou, Zhen Zhang, Yulei Mu

et al.

ACS Nano, Journal Year: 2024, Volume and Issue: 18(16), P. 10667 - 10687

Published: April 9, 2024

Cartilage injuries are escalating worldwide, particularly in aging society. Given its limited self-healing ability, the repair and regeneration of damaged articular cartilage remain formidable challenges. To address this issue, nanomaterials leveraged to achieve desirable outcomes by enhancing mechanical properties, optimizing drug loading bioavailability, enabling site-specific targeted delivery, orchestrating cell activities at nanoscale. This review presents a comprehensive survey recent research nanomedicine for repair, with primary focus on biomaterial design considerations advances. The commences an introductory overview intricate microenvironment further delves into key parameters crucial treating damage, including microstructure, surface charge, active targeting. focal point lies advances nano delivery systems nanotechnology-enabled 3D matrices repair. We discuss compositions properties these elucidate how materials impact cartilage. underscores pivotal role nanotechnology improving efficacy biomaterials utilized treatment damage.

Language: Английский

Citations

14