Exploration of the Key Pathways and Genes Involved in Osteoarthritis Genesis: Evidence from Multiple Platforms and Real-World Validation DOI Creative Commons
Hao Lv,

Jingkun Wang,

Yang Wan

и другие.

Journal of Inflammation Research, Год журнала: 2024, Номер Volume 17, С. 10223 - 10237

Опубликована: Дек. 1, 2024

Background: Osteoarthritis (OA), a degenerative and chronic joint disease, is essential for identifying novel biomarkers the clinical diagnosis of OA. Methods: We collected 35 OA patients 32 healthy controls from four cohorts 8 real-world samples our institute. The activation status 7530 signalling pathways was calculated via gene set enrichment analysis (GSEA) algorithm. Ten machine learning algorithms 101 algorithm combinations were further applied to recognize most diagnostic genes. KDELR3 chosen validation immunohistochemical staining determine its value in samples. Results: Sixteen pathways, namely, cellular respiration chain, protein transport, lysosomal endocytosis activated patients. A total types considered model, 58 successfully output. two-step model glmBoost plus RF had highest average AUC 0.95 composed LY86, SORL1, KDELR3, CSK, PTGS1, PTGS2. Preferable consistency mole real conditions observed all (GSE55235: Kappa=1.000, P < 0.001; GSE55457: Kappa=0.700, GSE82107: Kappa=0.643, =0.004; GSE1919: 0.001). expressed at higher levels than other genes, with help immunohistochemistry (IHC), we confirmed that presented high synovial tissues. infiltration immunocytes, macrophages, natural killer T cells might be involved effector memory CD4 (R pearson = 0.58, 0.001) 0.53, Conclusion: constructed validated six-gene learning, emerged as biomarker Keywords: osteoarthritis, tissue, staining,

Язык: Английский

Recent development of mitochondrial metabolism and dysfunction in osteoarthritis DOI Creative Commons
Pengchao Guo, Ahmad Alhaskawi, Safwat Adel Abdo Moqbel

и другие.

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Фев. 13, 2025

Osteoarthritis is a degenerative joint disorder characterized by cartilage degradation, synovial inflammation, and altered subchondral bone structure. Recent insights have identified mitochondrial dysfunction as pivotal factor in OA pathogenesis, contributing to chondrocyte apoptosis, oxidative stress, extracellular matrix degradation. Disruptions dynamics, including impaired biogenesis, mitophagy, metabolic shifts from phosphorylation glycolysis, exacerbate damage promoting the production of reactive oxygen species matrix-degrading enzymes such ADAMTS MMPs. This review explores molecular mechanisms underlying OA, emphasizing its role homeostasis inflammation. Furthermore, it highlights emerging therapeutic strategies targeting pathways, antioxidants, mitophagy enhancers, modulators, potential interventions mitigate disease progression, which offer promising avenues for advancing personalized disease-modifying treatments OA.

Язык: Английский

Процитировано

1
Bioengineered Mesenchymal Stem/Stromal Cells in Anti-Cancer Therapy: Current Trends and Future Prospects DOI Creative Commons

Jesús I. Gil-Chinchilla,

A. Zapata, José M. Moraleda

и другие.

Biomolecules, Год журнала: 2024, Номер 14(7), С. 734 - 734

Опубликована: Июнь 21, 2024

Mesenchymal stem/stromal cells (MSCs) are one of the most widely used cell types in advanced therapies due to their therapeutic potential regulation tissue repair and homeostasis, immune modulation. However, use cancer therapy is controversial: they can inhibit proliferation, but also potentially promote tumour growth by supporting angiogenesis, modulation milieu increasing stem invasiveness. This opposite behaviour highlights need for careful nuanced MSCs treatment. To optimize anti-cancer effects, diverse strategies have bioengineered enhance targeting properties or deliver drugs. In this review, we highlight uses therapy, particularly as carriers targeted treatments natural tumour-homing capabilities. We discuss MSC-derived extracellular vesicles improve efficiency drug molecule delivery cells. Ongoing clinical trials evaluating these setting stage future advances MSC-based It critical identify broad potent applications solid agent position them effective therapeutics evolving field therapy.

Язык: Английский

Процитировано

4
Betaine enhances SCAPs chondrogenic differentiation and promotes cartilage repair in TMJOA through WDR81 DOI Creative Commons
Meiyue Wang, Zhaoming Wu, Xiaoyu Zheng

и другие.

Stem Cell Research & Therapy, Год журнала: 2025, Номер 16(1)

Опубликована: Фев. 7, 2025

The cartilage tissue regeneration mediated with mesenchymal stem cells (MSCs) is considered as a viable strategy for temporomandibular joint osteoarthritis (TMJOA). Betaine has been confirmed to modulate the multidirectional differentiation of MSCs, while its effect on chondrogenic Stem Cells from Apical Papilla (SCAPs) unknown. Here, we explored effects and underlying mechanisms betaine SCAPs. was added SCAPs induction. potential assessed using Alcian Blue staining, Sirius Red staining main markers. In vivo were evaluated by rat TMJOA model. RNA-sequencing biological analyses performed select target genes processes involved. mechanism acts further explored. Betain-treated demonstrated stronger in vitro promoted repair vivo. enhanced expression WDR81 during chondrogenesis. overexpression SCAPs, depletion inhibited differentiation. addition, both treatment reduced intracellular reactive oxygen species levels increased mitochondrial membrane promotes provided an effective candidate treatment. may serve drug through mitophagy.

Язык: Английский

Процитировано

0
mRNA therapy: A new frontier in regenerative medicine DOI Creative Commons
Danna Xue, Yue Zhang,

Anran Shen

и другие.

Deleted Journal, Год журнала: 2025, Номер unknown

Опубликована: Фев. 27, 2025

Abstract Tissue regeneration has raised intensive attention due to its great significance in overcoming various diseases resulting from different injuries. Since the COVID‐19 pandemic, mRNA therapeutics have emerged as innovative strategies prevention and treatment of their unique advantages. Compared traditional regenerative strategies, therapy offers rapid translation into proteins with low production cost high modifiability. Herein, we discuss progress key processes therapy, focusing on therapeutic modification delivery carriers. The preclinical clinical studies for cardiac, lung, liver, kidney, locomotor system, skin lesions neurological disorders were summarized comprehensively. Developing reduce immunogenicity off‐target effects, well optimization system may accelerate pace translation.

Язык: Английский

Процитировано

0
Cathepsin K Inhibitors as Potential Drugs for the Treatment of Osteoarthritis DOI Open Access

Leyre Brizuela,

René Buchet, Carole Bougault

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(7), С. 2896 - 2896

Опубликована: Март 22, 2025

Links between cathepsin K and the pathophysiology of osteoarthritis (OA) can be established, not least because overabundance in serum OA patients upregulation degraded cartilage animal models OA. Chondrocytes, chondroclasts, or osteoclasts contribute to accumulated at diseased osteochondral junction. After a general presentation physiology, as well its degradation processes, we describe function effect on via type II collagen cleavage. An overview most promising inhibitors is then presented, together with their vitro effects. Although intensive research initially focused bone resorption, there growing interest potential these drugs prevent degradation. In this review, summarize pre-clinical clinical trials that support use treatment To date, no molecules are commercially available, although few have undergone trials, but believe development could broaden therapeutic arsenal for

Язык: Английский

Процитировано

0
The bone microenvironment: new insights into the role of stem cells and cell communication in bone regeneration DOI Creative Commons
Luca Dalle Carbonare, Mattia Cominacini, Elisabetta Trabetti

и другие.

Stem Cell Research & Therapy, Год журнала: 2025, Номер 16(1)

Опубликована: Апрель 12, 2025

Mesenchymal stem cells (MSCs) play a crucial role in bone formation and remodeling. Intrinsic genetic factors extrinsic environmental cues regulate their differentiation into osteoblasts. Within the microenvironment, complex network of biochemical biomechanical signals orchestrates homeostasis regeneration. In addition, crosstalk among MSCs, immune cells, neighboring cells-mediated by extracellular vesicles non-coding RNAs (such as circular micro RNAs) -profoundly influences osteogenic Recent studies have explored specific signaling pathways that contribute to effective regeneration, highlighting potential manipulating microenvironment enhance MSC functionality. The integration advanced biomaterials, gene editing techniques, controlled delivery systems is paving way for more targeted efficient regenerative therapies. Furthermore, artificial intelligence could improve tissue engineering, optimize biomaterial design, enable personalized treatment strategies. This review explores latest advancements emphasizing intricate interplay molecules. By providing comprehensive overview these mechanisms clinical implications, we aim shed light on future research directions this rapidly evolving field.

Язык: Английский

Процитировано

0
Therapeutic effect of three-dimensional hanging drop cultured human umbilical cord mesenchymal stem cells on osteoarthritis in rabbits DOI Creative Commons
Qiang Fu, Mei Han, Xiaoyu Dai

и другие.

Stem Cell Research & Therapy, Год журнала: 2024, Номер 15(1)

Опубликована: Сен. 18, 2024

Язык: Английский

Процитировано

2
Efficacy and safety of culture-expanded mesenchymal stromal cell therapy in the treatment of 4 types of inflammatory arthritis: a systematic review and meta-analysis of 36 randomized controlled trials DOI

Liuting Zeng,

Kailin Yang,

Ganpeng Yu

и другие.

Seminars in Arthritis and Rheumatism, Год журнала: 2024, Номер 68, С. 152498 - 152498

Опубликована: Июнь 29, 2024

Язык: Английский

Процитировано

1
Roles of Microenvironment on Mesenchymal Stem Cells Therapy for Osteoarthritis DOI Creative Commons
Haiyan Zhang,

Chaoying Jin,

Jiaqing Hua

и другие.

Journal of Inflammation Research, Год журнала: 2024, Номер Volume 17, С. 7069 - 7079

Опубликована: Окт. 1, 2024

Osteoarthritis (OA) induced microenvironmental alterations are a common and unavoidable phenomenon that greatly exacerbate the pathologic process of OA. Imbalances in synthesis degradation cartilage extracellular matrix (ECM) have been reported to be associated with an adverse microenvironment. Stem cell therapy is promising treatment for OA, mesenchymal stem cells (MSCs) main sources this therapy. With multispectral differentiation immunomodulation, MSCs can effectively regulate microenvironment articular cartilage, ameliorate inflammation, promote regeneration damaged ultimately alleviate OA symptoms. However, efficacy influenced by cavity microenvironments. This article reviews five microenvironments cavity, including inflammatory microenvironment, senescence hypoxic high glucose lipid environment, focus on positive negative effects fate MSCs. In regard, we emphasize mechanisms current use treatment, as well its limitations challenges.

Язык: Английский

Процитировано

1
Electrical Stimulation of Mesenchymal Stem Cells as a Tool for Proliferation and Differentiation in Cartilage Tissue Engineering: A Scaffold-Based Approach DOI Creative Commons

Nicolas Lehmenkötter,

Johannes Greven,

Frank Hildebrand

и другие.

Bioengineering, Год журнала: 2024, Номер 11(6), С. 527 - 527

Опубликована: Май 22, 2024

Electrical stimulation (ES) is a widely discussed topic in the field of cartilage tissue engineering due to its ability induce chondrogenic differentiation (CD) and proliferation. It shows promise as potential therapy for osteoarthritis (OA). In this study, we stimulated mesenchymal stem cells (MSCs) incorporated into collagen hydrogel (CH) scaffolds, consisting approximately 500,000 each, 1 h per day using 2.5 Vpp (119 mV/mm) 8 Hz sinusoidal signal. We compared cell count, morphology, CD on days 4, 7, 10. The results indicate proliferation, with an increase ranging from 1.86 9.5-fold, particularly 7. Additionally, signs were observed. had higher volume, while scaffolds showed shrinkage. ES groups, up-regulation type 2 aggrecan was found. contrast, SOX9 up-regulated control group, MMP13 strong up-regulation, indicating stress. addition lower stress levels, groups also more spheroidic shape. Overall, scaffold-based has achieve multiple outcomes. However, finding appropriate pattern crucial achieving successful chondrogenesis.

Язык: Английский

Процитировано

0