Comparative Analysis of Osteoarthritis Therapeutics: A Justification for Harnessing Retrospective Strategies via an Inverted Pyramid Model Approach DOI Creative Commons

Quinn T. Ehlen,

Jacob Jahn, R. Rizk

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(11), P. 2469 - 2469

Published: Oct. 28, 2024

In this review, we seek to explore two distinct approaches the clinical management of OA: a prospective approach, addressing primarily one’s genetic predisposition OA and generating early intervention options, retrospective aimed at halting or reversing progression post-symptom onset. The remains challenging, largely due limited availability preventative treatments failure existing therapies modify reverse underlying pathophysiology. approach involves identification markers associated with utilizes in vitro vivo models characterize disease mechanism. Further, focuses on identifying predispositions unique molecular subtypes develop individualized treatment plans based patient genotypes. While current literature investigating strategy has been notable, faces substantial challenges, such as extensive time burdens utilization testing that may not be economically feasible. Additionally, there is questionable justification for investigations, given OA’s relatively low mortality rates burden when contrasted diseases like specific forms cancer, which rely heavily approach. Alternatively, following symptom onset aims utilize novel therapeutics slow inflammatory cascade typically seen progression. These treatments, Hippo pathway inhibitors, have shown initial promise alleviating symptomology by modulating cellular processes preserve articular cartilage. comparison likely more cost-effective, widely applicable, does necessitate thorough invasive screening. However, must still weighed against typical natural history progression, frequently results total knee arthroplasty unacceptable outcomes 15–20% patients. From comparative analysis these approaches, review argues strategy, ideally lower economic greater accessibility, offers reasonable effective solution context management. Using similar other chronic diseases, suggest an “Inverted Pyramid” model algorithm, structured research development regimen prioritizes first, subsequent refinement resistance therapies. We argue reduce need while improving accessibility.

Language: Английский

Advances in cell therapy for orthopedic diseases: bridging immune modulation and regeneration DOI Creative Commons
Jing Wang,

Shenghao Xu,

Bo Chen

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 10, 2025

Orthopedic diseases pose significant challenges to public health due their high prevalence, debilitating effects, and limited treatment options. Additionally, orthopedic tumors, such as osteosarcoma, chondrosarcoma, Ewing sarcoma, further complicate the landscape. Current therapies, including pharmacological treatments joint replacement, address symptoms but fail promote true tissue regeneration. Cell-based which have shown successful clinical results in cancers other diseases, emerged a promising solution repair damaged tissues restore function tumors. This review discusses advances potential application of cell therapy for with particular focus on osteoarthritis, bone fractures, cartilage degeneration, We explore mesenchymal stromal cells (MSCs), chondrocyte transplantation, engineered immune induced pluripotent stem enhance regeneration by modulating response addressing inflammation. Ultimately, integration cutting-edge therapy, modulation, molecular targeting strategies could revolutionize providing hope patients seeking long-term solutions conditions.

Language: Английский

Citations

1
Extracellular Vesicles: A Novel Diagnostic Tool and Potential Therapeutic Approach for Equine Osteoarthritis DOI Creative Commons
Mohamed I. Elashry,

Julia Speer,

V. Le Saux

et al.

Current Issues in Molecular Biology, Journal Year: 2024, Volume and Issue: 46(11), P. 13078 - 13104

Published: Nov. 17, 2024

Osteoarthritis (OA) is a chronic progressive degenerative joint disease that affects significant portion of the equine population and humans worldwide. Current treatment options for OA are limited incompletely curative. Horses provide an excellent large-animal model studying human OA. Recent advances in field regenerative medicine have led to exploration extracellular vesicles (EVs)-cargoes microRNA, proteins, lipids, nucleic acids-to evaluate their diagnostic value terms progression severity, as well potential cell-free therapeutic approach EVs transmit molecular signals influence various biological processes, including inflammatory response, apoptosis, proliferation, cell communication. In present review, we summarize recent isolation identification EVs, use biologically active components biomarkers, distribution gap junction protein connexin 43. Moreover, highlight role mesenchymal stem cell-derived tool musculoskeletal disorders. This review aims comprehensive overview current understanding pathogenesis, diagnosis, strategies particular, roles biomarkers synovial fluid, chondrocytes, plasma early detection discussed.

Language: Английский

Citations

3
The Interaction Between Microbiota and Stem Cells on Progression of Osteoarthritis and Engineered Stem Cell for Enhancing Osteoarthritis Treatment DOI Creative Commons
Sidan Wang,

Haotian Fu,

Zheng Xu

et al.

International Journal of Nanomedicine, Journal Year: 2025, Volume and Issue: Volume 20, P. 3219 - 3234

Published: March 1, 2025

Osteoarthritis (OA) is characterized by the degeneration of articular cartilage caused several factors which novel most trends include microbiota. Specific microbiota and role in development OA less clear. The presumed to influence occurrence progression mainly via immune modulation. In recent years, bone marrow mesenchymal stem cells (MSCs) have shown great potential for treatment OA, however, therapeutic efficiency has been seriously affected harsh microenvironment joint cavity. At present, many strategies used enhance function MSCs, among them, engineering are a promising method. Therefore, this review focuses on latest research how affects cell repair, use engineered MSCs OA. addition, can exosomes as strategy treating Our provides comprehensive perspective therapy

Language: Английский

Citations

0
Exosomes derived from MSCs exposed to hypoxic and inflammatory environments slow intervertebral disc degeneration by alleviating the senescence of nucleus pulposus cells through epigenetic modifications DOI
Yongzhao Zhao, Longting Chen, Shuai Jiang

et al.

Bioactive Materials, Journal Year: 2025, Volume and Issue: 49, P. 515 - 530

Published: March 20, 2025

Language: Английский

Citations

0
Supermolecular poly-N-acryloyl glycinamide/polyglutamic acid/Fe3+ hydrogel incorporated with bioactive small extracellular vesicles promote diabetic wound healing by suppressing ferroptosis DOI
Wei Liu, Kangcheng Zhao, Feng Chen

et al.

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: unknown, P. 142313 - 142313

Published: March 1, 2025

Language: Английский

Citations

0
Mesenchymal stromal/stem cell-derived exosomes as a potential therapeutic approach to osteoarthritis combined with type 2 diabetes mellitus DOI Creative Commons

Siyi Xie,

Meiling Liu,

Ya‐Jie Kong

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: March 27, 2025

Osteoarthritis (OA) and type 2 diabetes mellitus (T2DM) often coexist due to shared risk factors high prevalence, but effective treatment methods are currently lacking. Mesenchymal stromal/stem cell-derived exosomes (MSC-Exos) have regenerative properties that can repair cartilage damage, lower blood sugar levels, improve pancreatic β cell function, showing great potential in tissue repair. This review primarily explores the application of MSC-Exos OA T2DM, mechanisms MSC-Exos, therapeutic strategies engineered exosomes. Although MSC-Exo therapy shows promising potential, further research is needed validate its safety feasibility.

Language: Английский

Citations

0
LRP1 Mediates Endocytosis Activity and Is a Potential Therapeutic Target in Osteoarthritis DOI Creative Commons
Yuangang Wu, Kaibo Sun, Mingyang Li

et al.

Orthopaedic Surgery, Journal Year: 2025, Volume and Issue: unknown

Published: April 2, 2025

Osteoarthritis (OA) is a degenerative disease characterized by cartilage abrasion and pain, affecting millions globally. However, current treatments focus on symptom management rather than modifying development. Recent studies have indicated that low-density lipoprotein receptor-related protein 1 (LRP1) associated with maintaining homeostasis through its involvement in endocytosis signaling pathways. LRP1 facilitates the removal of extracellular matrix (ECM)-degrading enzymes, including disintegrin metalloproteinase thrombospondin motifs (ADAMTSs) metalloproteinases (MMPs), thereby protecting against excessive breakdown. OA shows increased shedding LRP1, leading to reduced endocytic capacity elevated levels these contributing accelerated ECM also involved key pathways, such as Wnt/β-catenin, transforming growth factor-beta (TGF-β), nuclear factor-kappa B (NF-κB), which regulate processes like chondrocyte proliferation, apoptosis, differentiation, autophagy. Dysregulation combined impaired LRP1-mediated endocytosis, fosters catabolic environment osteoarthritic cartilage. Emerging therapies targeting gene interventions, exosome-based therapies, small-molecule modulators, show potential restoring function, reducing degradation, promoting joint repair. This review emphasizes significance development explores therapeutic target for creating disease-modifying strategies maintain integrity enhance patient well-being.

Language: Английский

Citations

0
High-yield BMSCs-derived exosomes by the 3D culture system to enhance the skin wound repair DOI Creative Commons
Jie Wu, Siqi Li, Hao Wang

et al.

Regenerative Biomaterials, Journal Year: 2025, Volume and Issue: 12

Published: Jan. 1, 2025

Wound defects pose a substantial challenge in clinical practice, often resulting prolonged healing times and an elevated risk of infection. Insufficient vascularization is critical factor that adversely affects wound healing. Exosomes obtained from bone mesenchymal stem cells (BMSC-exos) have demonstrated significant promise accelerating tissue repair by promoting angiogenesis. However, their limited yield suboptimal biological functions impede widespread application enhancing Prior research has indicated 3D cultures can boost exosome secretion when compared to conventional 2D cultures. the currently prevalent culture methods necessitate expensive equipment or cumbersome procedures. This study investigates cost-effective user-friendly system developed using gelatin methacrylate (GelMA). Our findings indicate 5% concentration GelMA provides optimal environment for BMSCs. Furthermore, we observed significantly delays senescence BMSCs, thereby creating favorable conditions sustained production exosomes. Additionally, cultivation potential enhance angiogenic capabilities. In vivo experiments further confirmed BMSC-exos exhibit enhanced capabilities promote These results suggest GelMA-based offer novel strategy both industrial

Language: Английский

Citations

0
Therapeutic potential of stem cell-derived exosomes for bone tissue regeneration around prostheses DOI Creative Commons
Q Li, Feng‐Juan Lyu, Zhantao Deng

et al.

Journal of Orthopaedic Translation, Journal Year: 2025, Volume and Issue: 52, P. 85 - 96

Published: April 11, 2025

Language: Английский

Citations

0
Exosomes Extracted from Human Umbilical Cord MSCs Contribute to Osteoarthritic Cartilage and Chondrocytes Repair Through Enhancing Autophagy While Suppressing the Wnt/β-Catenin Pathway DOI
Sharon Qin, Aijie Zhang, Lian Duan

et al.

Tissue Engineering and Regenerative Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: April 15, 2025

Language: Английский

Citations

0