Nrf2-mediated anti-inflammatory polarization of macrophages as therapeutic targets for osteoarthritis

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Авг. 12, 2022

Macrophages are the most abundant immune cells within synovial joints, and also main innate effector triggering initial inflammatory responses in pathological process of osteoarthritis (OA). The transition macrophages between pro-inflammatory anti-inflammatory phenotypes can play a key role building intra-articular microenvironment. cascade induced by TNF-α, IL-1β, IL-6 is closely related to M1 macrophages, resulting production pro-chondrolytic mediators. However, IL-10, IL1RA, CCL-18, IGF, TGF M2 leading protection cartilage promoted regeneration. inhibition NF-κB signaling pathway central OA treatment via controlling while nuclear factor erythroid 2-related 2 (Nrf2) appears not attract widespread attention field. Nrf2 transcription encoding large number antioxidant enzymes. activation have effects, which complex crosstalk with pathway. inhibit polarization promote through potential transductions including TGF-β/SMAD, TLR/NF-κB, JAK/STAT pathways, regulation or cooperation Notch, NLRP3, PI3K/Akt, MAPK signaling. And expression heme oxygenase-1 (HO-1) negative for be mechanisms promotion. Furthermore, candidates activating phenotype reviewed this work, such as itaconate fumarate derivatives, curcumin, quercetin, melatonin, mesenchymal stem cells, low-intensity pulsed ultrasound.

Язык: Английский

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Regeneration of articular cartilage defects: Therapeutic strategies and perspectives

Journal of Tissue Engineering, Год журнала: 2023, Номер 14

Опубликована: Янв. 1, 2023

Articular cartilage (AC), a bone-to-bone protective device made of up to 80% water and populated by only one cell type (i.e. chondrocyte), has limited capacity for regeneration self-repair after being damaged because its low density, alymphatic avascular nature. Resulting repair defects, such as osteoarthritis (OA), is highly challenging in clinical treatment. Fortunately, the development tissue engineering provides promising method growing cells using hydrogels or porous scaffolds. In this paper, we review therapeutic strategies AC including current treatment methods, engineering/regenerative strategies, recent advances biomaterials, present emphasize on perspectives gene regulation therapy noncoding RNAs (ncRNAs), circular RNA (circRNA) microRNA (miRNA).

Язык: Английский

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Targeting macrophage polarization as a promising therapeutic strategy for the treatment of osteoarthritis

International Immunopharmacology, Год журнала: 2023, Номер 116, С. 109790 - 109790

Опубликована: Фев. 1, 2023

Язык: Английский

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Bioactive Injectable and Self‐Healing Hydrogel Via Cell‐Free Fat Extract for Endometrial Regeneration

Small, Год журнала: 2023, Номер 19(30)

Опубликована: Апрель 10, 2023

The damaged endometrium and the formation of fibrosis are key barriers to pregnancy further lead infertility. However, how promote repair is always a challenge. Here, bioactive injectable self-healing hydrogel developed by physically combination thiolated polyethylene (PEG), Cu2+ cell-free fat extract (CEFFE, CF) for endometrial regeneration fertility. By inheriting advantages various active proteins contained in CEFFE, it could induce overall microenvironment intrauterine adhesion (IUA). In vitro, CF@Cu-PEG reduces cell apoptosis more than 50%, increases angiogenesis 92.8%. IUA mouse, injection significantly rate uterine hydrometra prevents fibrosis. Remarkably, contributes microstructure, especially number pinopodes, improves receptivity, mice from 7.14% 66.67%. summary, through CEFFE Cu-PEG, construction loaded not only inhibits IUA, but also induces self-repair cells situ fertility, providing new strategy clinical application.

Язык: Английский

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Oleic and linoleic acids induce oxidative stress in chondrocytes by inhibiting autophagy‐regulated ciliogenesis

View, Год журнала: 2024, Номер 5(4)

Опубликована: Июнь 28, 2024

Abstract The lack of a cure for osteoarthritis (OA), prevalent joint disease among older individuals, remains an ongoing challenge. Obesity is common risk factor OA. Chondrocyte autophagy plays crucial role in delaying the onset Our previous studies have demonstrated significant elevation levels oleic acid (OLA) and linoleic (LA) synovial fluid (SF) patients with OA obesity compared to those alone, inhibitory effect these molecules on activation autophagy. Accumulating evidence indicates reciprocal regulatory relationship between ciliogenesis; however, whether autophagy‐mediated ciliogenesis pathogenesis unclear. In this study, we aimed determine OLA LA affect development via regulation chondrocyte ciliogenesis. We found that both inhibited process chondrocytes. Moreover, intracellular calcium reactive oxygen species (ROS) increased simultaneously. Further, explored Activation by rapamycin significantly attenuated inhibition caused LA. Importantly, downregulation AKT mTOR expression chondrocytes reversed ROS‐accumulation‐mediated inflammation induced Taken together, our results suggest induce calcium‐overload‐driven ROS accumulation ciliogenic disorders during pathogenesis. These findings demonstrate targeting protective strategy

Язык: Английский

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Clinical efficacy of cell-free fat extract and its effects on bone marrow edema in patients with early to mid-stage knee osteoarthritis: a clinical trial in comparison with hyaluronic acid

Journal of Orthopaedic Surgery and Research, Год журнала: 2025, Номер 20(1)

Опубликована: Фев. 9, 2025

Abstract Background Previous studies have shown that hyaluronic acid can delay the progression of knee osteoarthritis. Existing research has extracted a bright red fluid called cell-free fat extract from human adipose tissue, which may play an important role in delaying By comparing with intra-articular injection acid, this study aimed to evaluate effects CEFFE on both clinical efficacy and reduction bone marrow edema patients early mid-stage Methods A total 48 KOA (Kellgren-Lawrence grade II-III) symptoms were randomly divided into group (24 cases) HA cases). The received five injections (2 ml, 1 time/week), ml/10 mg, time/week). All underwent assessments using rating scales, including VAS, WOMAC Lysholm Knee Score. These conducted at pre-treatment 3-week, 6-week, 3-month, 6-month follow-up timepoints post-treatment. was evaluated after treatment. changes subchondral before 6 months treatment assessed by grading BME MRI affected knees. Results 52 knees 46 included final analysis. Comparison VAS score, score between two groups revealed differences 3 weeks post-treatment not statistically significant ( P > 0.05). For weeks, months, post-treatment, lower than < higher Compared pre-treatment, scores all time points At significantly better showed reduced different degrees groups, being more pronounced Conclusion This demonstrated joint could enhance durability tissue-specific cells (especially chondrocytes) improve cellular metabolic processes, preventing continued Both found However, effective achieving these outcomes.

Язык: Английский

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Advances of Biological Therapies in Premature Ovarian Insufficiency

Advances in Clinical Medicine, Год журнала: 2025, Номер 15(04), С. 2325 - 2333

Опубликована: Янв. 1, 2025

Язык: Английский

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Cell-free fat extract restores hair loss: a novel therapeutic strategy for androgenetic alopecia

Stem Cell Research & Therapy, Год журнала: 2023, Номер 14(1)

Опубликована: Авг. 23, 2023

Androgenetic alopecia (AGA) is one of the most common hair loss diseases worldwide. However, current treatments including medicine, surgery, and stem cells are limited for various reasons. Cell-free fat extract (CEFFE), contains cell factors, may have potential abilities in treating AGA. This study aims to evaluate safety, effectiveness underlying mechanism CEFFE AGA.Sex hormone evaluation, immunogenicity assay genotoxicity were conducted CEFFE. In vivo study, male C57BL/6 mice injected subcutaneously with dihydrotestosterone (DHT) treated different concentration 18 days (five groups n = 12 each group: Control, Model, CEFFELow, CEFFEMiddle, CEFFEHigh). Anagen entry rate coverage percentage analyzed through continuously taken gross photographs. The angiogenesis proliferation follicle evaluated by hematoxylin-eosin, anti-CD31, anti-Ki67 staining. vitro dermal papilla (DPCs) incubated concentrations CEFFE, DHT, or + followed CCK-8 flow cytometry cycle apoptosis. intracellular DHT level assessed enzyme-linked immunosorbent assay. expression 5α-reductase type II, 3α-hydroxysteroid dehydrogenase androgen receptor reverse transcription-quantitative polymerase chain reaction (RT-qPCR) or/and western blot.In CEFFE-treated mice, an increase anagen was observed. number CD31-positive capillaries Ki67-positive increased, suggesting that promoted DPCs, modulated arrest, inhibited apoptosis caused reduced downregulated AR.CEFFE a novel effective treatment option AGA producing increased density growth rate. proposed mechanisms DHT/AR pathway regulation regional ability.

Язык: Английский

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Recombinant human annexin A5 accelerates diabetic wounds healing by regulating skin inflammation

Regenerative Therapy, Год журнала: 2024, Номер 27, С. 342 - 353

Опубликована: Апрель 17, 2024

One of the key obstacles to healing diabetic wound is persistence active inflammation. We previously demonstrated potential cell-free fat extract (CEFFE) promote wounds, and annexin A5 (A5) a crucial anti-inflammatory protein within CEFFE. This study aimed evaluate therapeutic in wounds. was loaded into GelMA hydrogels applied skin wounds mice vivo. The with treatment GelMA-A5 were observed for 14 days evaluated by histological analysis. Accessment inflammation regulation conducted through anti-CD68 staining, anti-CD86 anti-CD206 qRT-PCR tissue. In presence A5, macrophages stimulated lipopolysaccharide (LPS) vitro, detected qRT-PCR, flow cytometry, immunocytofluorescence staining. Besides, epithelial cells co-cultured epithelialization CCK-8 assay cell migration assay. could regulate inflammations promoting transition from M1 M2 phenotype. vitro experiments that exerted significant effect on reducing pro-inflammatory factors inhibiting polarization M0 toward significantly promoted cells. Annexin has impact macrophage promotion epithelialization.

Язык: Английский

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Pro-vasculogenic Fibers by PDA-Mediated Surface Functionalization Using Cell-Free Fat Extract (CEFFE)

Biomacromolecules, Год журнала: 2024, Номер 25(3), С. 1550 - 1562

Опубликована: Фев. 27, 2024

Formation of adequate vascular network within engineered three-dimensional (3D) tissue substitutes postimplantation remains a major challenge for the success biomaterials-based regeneration. To better mimic in vivo angiogenic and vasculogenic processes, nowadays increasing attention is given to strategy functionalizing biomaterial scaffolds with multiple bioactive agents. Aimed at engineering electrospun biomimicking fibers pro-vasculogenic capability, this study was proposed functionalize polycaprolactone/gelatin (PCL/GT) by cell-free fat extract (CEFFE or FE), newly emerging natural "cocktail" cytokines growth factors extracted from human adipose tissue. This achieved having PCL/GT fiber surface coated polydopamine (PDA) followed PDA-mediated immobilization FE generate FE-PDA@PCL/GT. It found that PDA-coated fibrous mat exhibited high FE-loading efficiency (∼90%) enabled be released highly sustained manner. The FE-PDA@PCL/GT possess improved cytocompatibility, as evidenced enhanced cellular proliferation, migration, RNA protein expressions (e.g., CD31, vWF, VE-cadherin) umbilical vein endothelial cells (huvECs) used. Most importantly, were enormously stimulate tube formation vitro, microvascular development ovo chick chorioallantoic membrane (CAM) assay, vascularization 3D construct rat subcutaneous embedding model. highlights potential currently versatile platform vascularized constructs functional

Язык: Английский

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