Exploring the translational potential of PLGA nanoparticles for intra-articular rapamycin delivery in osteoarthritis therapy DOI Creative Commons
Jian-Chao Ma, Tingting Luo,

Binyang Feng

et al.

Journal of Nanobiotechnology, Journal Year: 2023, Volume and Issue: 21(1)

Published: Oct. 4, 2023

Abstract Osteoarthritis (OA) is a prevalent joint disease that affects all the tissues within and currently lacks disease-modifying treatments in clinical practice. Despite potential of rapamycin for OA alleviation, its application hindered by challenge achieving therapeutic concentrations, which necessitates multiple injections per week. To address this issue, was loaded into poly(lactic-co-glycolic acid) nanoparticles (RNPs), are nontoxic, have high encapsulation efficiency exhibit sustained release properties treatment. The RNPs were found to promote chondrogenic differentiation ATDC5 cells prevent senescence caused oxidative stress primary mouse articular chondrocytes. Moreover, capable alleviate metabolism homeostatic imbalance chondrocytes both monolayer 3D cultures under inflammatory or stress. In destabilization medial meniscus (DMM) model, intra-articular injection effectively mitigated cartilage destruction, osteophyte formation, hypertrophy, synovial inflammation, pain. Our study demonstrates feasibility using as clinically translational therapy progression post-traumatic OA. Graphical abstract

Language: Английский

Applications of Hydrogels in Osteoarthritis Treatment DOI Creative Commons
Xin Gan, Xiaohui Wang, Yiwan Huang

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(4), P. 923 - 923

Published: April 22, 2024

This review critically evaluates advancements in multifunctional hydrogels, particularly focusing on their applications osteoarthritis (OA) therapy. As research evolves from traditional natural materials, there is a significant shift towards synthetic and composite known for superior mechanical properties enhanced biodegradability. spotlights novel such as injectable microneedle technology, responsive which have revolutionized OA treatment through targeted efficient therapeutic delivery. Moreover, it discusses innovative hydrogel including protein-based superlubricating potential to reduce joint friction inflammation. The integration of bioactive compounds within hydrogels augment efficacy also examined. Furthermore, the anticipates continued technological deeper understanding hydrogel-based therapies. It emphasizes provide tailored, minimally invasive treatments, thus highlighting critical role advancing dynamic field biomaterial science management.

Language: Английский

Citations

15
Logic‐Based Strategy for Spatiotemporal Release of Dual Extracellular Vesicles in Osteoarthritis Treatment DOI
Shiyu Li, Weihan Zheng, Wenfeng Deng

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(26)

Published: May 5, 2024

Abstract To effectively treat osteoarthritis (OA), the existing inflammation must be reduced before cartilage damage can repaired; this cannot achieved with a single type of extracellular vesicles (EVs). Here, hydrogel complex logic‐gates function is proposed that spatiotemporally controlled release two types EVs: interleukin 10 (IL‐10) + EVs to promote M2 polarization macrophage, and SRY‐box transcription factor 9 (SOX9) increase matrix synthesis. Following dose‐of‐action screening, dual are loaded into metalloporoteinase 13 (MMP13)‐sensitive self‐assembled peptide (KM13E) polyethylene glycol diacrylate/gelatin methacryloyl‐hydrogel microspheres (PGE), respectively. These materials mixed form “microspheres‐in‐gel” KM13E@PGE system. In vitro, abruptly released IL‐10 after 3 days slowly SOX9 for more than 30 days. vivo, increased CD206 macrophage proportion in synovial tissue decreased tumor necrosis factor‐α IL‐1β levels. The aggrecan expressions tissues significantly elevated following subsidence. This performance not using anti‐inflammatory or repair therapy alone. present study provides an injectable, integrated delivery system spatiotemporal control EVs, may inspire strategies OA treatment.

Language: Английский

Citations

15
Sakuranetin reduces inflammation and chondrocyte dysfunction in osteoarthritis by inhibiting the PI3K/AKT/NF-κB pathway DOI Open Access
Xiaofeng Deng, Yunkun Qu, Mengwei Li

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 171, P. 116194 - 116194

Published: Jan. 22, 2024

Osteoarthritis (OA) is a prevalent degenerative disease that impairs limb function, and its pathogenesis closely related to inflammation. Sakuranetin (SK) cherry flavonoid phytoalexin with potent anti-inflammatory, anti-oxidant, ant-ifungal properties. In recent studies, phytoalexin-related medicines have shown promise in the treatment of OA. However, effects SK on chondrocyte inflammation chondrogenesis process remained unexplored, as functions OA treatment. This study sought confirm therapeutic rat model reveal potential mechanisms for protecting chondrocytes. The relevant were analyzed by network pharmacology analysis. Chondrocytes subjected IL-1β intervention simulate an inflammatory environment received Then, anabolism, catabolism, markers detected western blot, qPCR, elisa, immunofluorescence. Chondrogenic ability was evaluated micromass 3D culture assays. rats treated destabilization medial meniscus (DMM) surgery establish intra-articular injections subsequently. Histological staining, immunohistochemistry, micro-CT performed analyze structural morphological changes cartilage subchondral bone. chondrocytes, reduced chondrogenic ability, promoted exacerbated triggering PI3K/AKT/NF-κB pathway, whereas partially rescued these negative effects. vivo, effectively alleviated degeneration bone, thereby delaying progression summary, alleviates promotes inhibiting improving progression.

Language: Английский

Citations

12
Senolytic therapeutics: An emerging treatment modality for osteoarthritis DOI
Md. Meraj Ansari, Mrinmoy Ghosh, Dong‐Sun Lee

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 96, P. 102275 - 102275

Published: March 15, 2024

Language: Английский

Citations

12
Mesenchymal Stem Cell-Derived Exosomes as a Treatment Option for Osteoarthritis DOI Open Access

Anupama Vadhan,

Tanvi Gupta, Wen‐Li Hsu

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(17), P. 9149 - 9149

Published: Aug. 23, 2024

Osteoarthritis (OA) is a leading cause of pain and disability worldwide in elderly people. There critical need to develop novel therapeutic strategies that can effectively manage improve the quality life for older Mesenchymal stem cells (MSCs) have emerged as promising cell-based therapy age-related disorders due their multilineage differentiation strong paracrine effects. Notably, MSC-derived exosomes (MSC-Exos) gained significant attention because they recapitulate MSCs into benefits without causing any associated risks compared with direct cell transplantation. These help transport bioactive molecules such proteins, lipids, nucleic acids, which influence various cellular processes related tissue repair, regeneration, immune regulation. In this review, we provided an overview MSC-Exos considerable treatment option osteoarthritis. This review will go over underlying mechanisms by may alleviate pathological hallmarks OA, cartilage degradation, synovial inflammation, subchondral bone changes. Furthermore, summarized current preclinical evidence highlighted results from vitro vivo studies, well progress clinical trials using treat OA.

Language: Английский

Citations

11
Pain Management Strategies in Osteoarthritis DOI Creative Commons
Luca Farinelli, Michele Riccio, Antonio Gigante

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(4), P. 805 - 805

Published: April 4, 2024

Pain is the major symptom of osteoarthritis (OA) and an important factor in strategies to manage this disease. However, current standard care does not provide satisfactory pain relief for many patients. The pathophysiology OA complex, its presentation as a clinical syndrome associated with pathologies multiple joint tissues. Treatment options are generally classified pharmacologic, nonpharmacologic, surgical, complementary and/or alternative, typically used combination achieve optimal results. goals treatment alleviation symptoms improvement functional status. Several studies exploring various directions management, including tissue regeneration techniques, personalized medicine, targeted drug therapies. aim present narrative review extensively describe all treatments available practice, further describing most innovative Advancements understanding molecular genetic aspects may lead more effective tailored approaches future.

Language: Английский

Citations

9
Integrated analysis of bioinformatics, mendelian randomization, and experimental validation reveals novel diagnostic and therapeutic targets for osteoarthritis: progesterone as a potential therapeutic agent DOI Creative Commons

Ziyu Weng,

Chenzhong Wang,

Bo Liu

et al.

Journal of Orthopaedic Surgery and Research, Journal Year: 2025, Volume and Issue: 20(1)

Published: Jan. 23, 2025

Osteoarthritis (OA), characterized by progressive degeneration of cartilage and reactive proliferation subchondral bone, stands as a prevalent condition in orthopedic clinics. However, the precise mechanisms underlying OA pathogenesis remain inadequately explored. In this study, Random Forest (RF), Least Absolute Shrinkage Selection Operator (LASSO), Support Vector Machine-Recursive Feature Elimination (SVM-RFE) machine learning techniques were employed to identify hub genes. Based on these genes, an Artificial Neural Network (ANN) diagnostic model was constructed. The Drug Signatures Database (DSigDB) utilized screen small-molecule drugs targeting molecular docking analyses dynamics simulations explore validate binding interactions between proteins drugs. Expression changes genes under inflammatory conditions validated through vitro experiments, including RT-qPCR Western blotting, therapeutic effects identified drug chondrocytes further verified vitro. Lastly, Mendelian randomization analysis conducted examine causal association progesterone levels various phenotypes. we three genes: interleukin 1 receptor-associated kinase 3 (IRAK3), integrin subunit beta-like (ITGBL1), Ras homolog family member U (RHOU). An constructed based demonstrated excellent performance both training validation phases. Screening with key proteins. Molecular using AutoDock Vina revealed that exhibited energies ≤ -7 kcal/mol each proteins, indicating strong affinity. Furthermore, stability strength interactions. blotting confirmed downregulation IL-1β-treated chondrocytes. also potential Finally, established significant multiple our IRAK3, ITGBL1, RHOU novel targets for OA. Progesterone preliminarily Further research is crucial elucidate specific involved.

Language: Английский

Citations

1
Blockage of Osteopontin‐Integrin β3 Signaling in Infrapatellar Fat Pad Attenuates Osteoarthritis in Mice DOI Creative Commons
Bingyang Dai, Yuwei Zhu, Xu Li

et al.

Advanced Science, Journal Year: 2023, Volume and Issue: 10(22)

Published: May 23, 2023

Abstract The knowledge of osteoarthritis (OA) has nowadays been extended from a focalized cartilage disorder to multifactorial disease. Although recent investigations have reported that infrapatellar fat pad (IPFP) can trigger inflammation in the knee joint, mechanisms behind role IPFP on OA progression remain be defined. Here, dysregulated osteopontin (OPN) and integrin β 3 signaling are found specimens both human mice. It is further demonstrated IPFP‐derived OPN participates progression, including activated matrix metallopeptidase 9 chondrocyte hypertrophy fibrosis. Motivated by these findings, an injectable nanogel fabricated provide sustained release siRNA Cd61 ( RGD− Nanogel/siRNA ) targets integrins. Nanogel possesses excellent biocompatibility desired targeting abilities vitro vivo. Local injection robustly alleviates degeneration, suppresses advancement tidemark, reduces subchondral trabecular bone mass Taken together, this study provides avenue for developing therapy mitigate via blocking OPN‐integrin IPFP.

Language: Английский

Citations

21
“Bone-SASP” in Skeletal Aging DOI Creative Commons

Ching‐Lien Fang,

Bin Liu, Mei Wan

et al.

Calcified Tissue International, Journal Year: 2023, Volume and Issue: 113(1), P. 68 - 82

Published: May 31, 2023

Abstract Senescence is a complex cell state characterized by stable cycle arrest and unique secretory pattern known as the senescence-associated phenotype (SASP). The SASP factors, which are heterogeneous tissue specific, normally include chemokines, cytokines, growth adhesion molecules, lipid components that can lead to multiple age-associated disorders eliciting local systemic consequences. skeleton highly dynamic organ changes constantly in shape composition. Senescent cells bone marrow produce diverse factors induce alterations of through paracrine effects. Herein, we refer cell-associated “bone-SASP.” In this review, describe current knowledge cellular senescence SASP, focusing on role senescent mediating pathologies during natural aging premature syndromes. We also summarize bone-SASP glucocorticoids-induced damage. addition, discuss development osteoarthritis, highlighting mechanisms drives subchondral metabolic syndrome-associated osteoarthritis.

Language: Английский

Citations

20
Role of Wnt signaling pathway in joint development and cartilage degeneration DOI Creative Commons

Xinyan Li,

Yuanyuan Han,

Guimiao Li

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 11

Published: June 8, 2023

Osteoarthritis (OA) is a prevalent musculoskeletal disease that affects approximately 500 million people worldwide. Unfortunately, there currently no effective treatment available to stop or delay the degenerative progression of joint disease. Wnt signaling pathways play fundamental roles in regulation growth, development, and homeostasis articular cartilage. This review aims summarize role development during embryonic stages cartilage maintenance throughout adult life. Specifically, we focus on aberrant mechanical loading inflammation as major players OA progression. Excessive load activates pathway chondrocytes, resulting chondrocyte apoptosis, matrix destruction other osteoarthritis-related changes. Additionally, discuss emerging Wnt-related modulators present an overview treatments targeting signaling. Ultimately, this provides valuable insights towards discovering new drugs gene therapies for diagnosing treating osteoarthritis diseases.

Language: Английский

Citations

20