Molecular Processes in Chondrocyte Biology

Komori, Toshihisa

doi:10.3390/ijms21114161

Cited by 7 publications

(2 citation statements)

References 17 publications

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“…We also demonstrated the effect of a healthy synovial membrane (SM) on joint homeostasis in OA. We investigated the mechanism of the EV-mediated specific delivery of miR-150-3p from FLSs to chondrocytes, the primary effector cells in the synovium and cartilage that participate in joint homeostasis [ 32 , 33 ]. We also investigated the mechanism of joint homeostasis through the involvement of the Trim14/NF-κB/interferon-β (IFN-β) axis in the innate immune response.…”

Section: Introductionmentioning

confidence: 99%

Extracellular Vesicle-Mediated miR-150-3p Delivery in Joint Homeostasis: A Potential Treatment for Osteoarthritis?

Wang

Shen

Zhang

et al. 2022

Cells

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Background: The disruption of joint homeostasis is a critical event during the process of joint injury in osteoarthritis (OA). As regulatory molecules, microRNAs (miRNAs) can be released from secretory cells and delivered to recipient cells through extracellular vesicles (EVs), thereby playing an important role in regulating joint homeostasis. We hypothesized that the fibroblast-like synoviocytes (FLSs) in healthy joints could release EVs enriched in miRNAs that can maintain joint homeostasis by regulating the signal transduction pathways in the joints, whereby the articular cartilage (AC) is protected from degeneration, and OA progression is delayed. Methods: Via high-throughput sequencing and qPCR, we found that miR-150-3p was enriched in the circulating EVs in healthy rats. Next, we established an in vitro cell model in which chondrocytes were cultured with (i) FLSs transfected with miR-150-3p mimics or (ii) EVs released by FLSs (FLS–EVs) inside the healthy synovial membrane (SM). The transportation mechanism from FLSs to chondrocytes was studied using the EV inhibitor GW4869, and the FLSs were transfected with a miR-150-3p mimic or inhibitor. To assess the therapeutic effect of miR-150-3p-carrying EVs (EVs-150) in vivo, healthy FLS-derived EVs (H-FLS–EVs) were injected into the tail vein of rats with OA at various stages of the pathogenesis and evaluated for the progression of OA. Results: The chondrocytes could uptake fluorescent-labeled miR-150-3p mimics and FLS–EVs, and GW4869 suppressed this uptake. The overexpression of miR-150-3p could significantly reduce the concentrations of pro-inflammatory cytokines in the cell culture medium and the expression of the miR-150-3p target T cell receptor-interacting molecule 14 (Trim14), as well as the innate immune-related factors, including nuclear factor kappa B (NF-κB) and interferon-β (IFN-β). Similarly to the in vitro findings, the miR-150-3p level in the serum EVs was significantly upregulated among the EV-treated rats. In the AC of the OA rat model injected with H-FLS–EVs, the joint degeneration was suppressed, and Type II collagen (COLII) and aggrecan (ACAN) were significantly upregulated, whereas the innate immune-related factors Trim14, NF-κB, and IFN-β were downregulated compared with the levels in the untreated OA rats. Notably, the suppression of joint degeneration was more significant when H-FLS–EVs were administered at the early stages of OA rather than the late stages. Conclusion: H-FLS–EVs protect chondrocyte function and maintain joint homeostasis by modulating the innate immune response by suppressing the Trim14/NF-κB/IFNβ axis. These effects are achieved through the EV-mediated transport of miR-150-3p from the FLSs to the chondrocytes. Our findings show that EV-mediated miR-150-3p can be used to suppress OA, thus providing a novel therapeutic strategy. Additionally, the EV-mediated miR-150-3p transport may also serve as a potential biomarker in the diagnosis, treatment, and prognosis of OA.

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Section: Introductionmentioning

confidence: 99%

Extracellular Vesicle-Mediated miR-150-3p Delivery in Joint Homeostasis: A Potential Treatment for Osteoarthritis?

Wang

Shen

Zhang

et al. 2022

Cells

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“…The fluid nourishes chondrocytes from synovium and subchondral bone ( Figure 1D ) ( Armiento et al, 2018 ; Messina et al, 2019 ). With the stagnation of the premature stage, chondrocytes intervene in the perpetual balance of articular cartilage vitally ( Komori, 2020 ). Chondrocytes synthesize and secrete collagen, polysaccharides, and their derivatives to construct ECM.…”

Section: Structure Of Articular Cartilage and Synoviummentioning

confidence: 99%

Development of Nanomaterials to Target Articular Cartilage for Osteoarthritis Therapy

Rao

Shi

2022

Front. Mol. Biosci.

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Osteoarthritis (OA) is an obstinate, degradative, and complicated disease that has drawn much attention worldwide. Characterized by its stubborn symptoms and various sequela, OA causes much financial burden on both patients and the health system. What’s more, conventional systematic therapy is not effective enough and causes multiple side effects. There’s much evidence that nanoparticles have unique properties such as high penetration, biostability, and large specific surface area. Thus, it is urgent to exploit novel medications for OA. Nanomaterials have been sufficiently studied, exploiting diverse nano-drug delivery systems (DDSs) and targeted nano therapeutical molecules. The nanomaterials are primarily intra-articular injected under the advantages of high topical concentration and low dosage. After administration, the DDS and targeted nano therapeutical molecules can specifically react with the components, including cartilage and synovium of a joint in OA, furthermore attenuate the chondrocyte apoptosis, matrix degradation, and macrophage recruitment. Thus, arthritis would be alleviated. The DDSs could load with conventional anti-inflammatory drugs, antibodies, RNA, and so on, targeting chondrocytes, synovium, or extracellular matrix (ECM) and releasing the molecules sequentially. The targeted nano therapeutical molecules could directly get to the targeted tissue, alleviating the inflammation and promoting tissue healing. This review will comprehensively collect and evaluate the targeted nanomaterials to articular cartilage in OA.

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Hierarchical Composite Scaffold with Deferoxamine Delivery System to Promote Bone Regeneration via Optimizing Angiogenesis

Wang,

Zha,

Chen

et al. 2024

Adv Healthcare Materials

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A bone defect refers to the loss of bone tissue caused by trauma or lesions. Bone defects result in high morbidity and deformity rates worldwide. Autologous bone grafting has been widely applied in clinics as the gold standard of treatment; however, it has limitations. Hence, bone tissue engineering (BTE) has been proposed and developed as a novel therapeutic strategy for treating bone defects. Rapid and effective vascularization is essential for bone regeneration. In this study, a hierarchical composite scaffold with deferoxamine (DFO) delivery system, DFO@GMs‐pDA/PCL‐HNTs (DGPN), was developed, focusing on vascularized bone regeneration. The hierarchical structure of DGPN imitates the microstructure of natural bone and interacts with the local extracellular matrix (ECM), facilitating cell adhesion and proliferation. The addition of 1 wt% of halloysite nanotubes (HNTs) improved the material properties. Hydrophilic and functional groups conferred by polydopamine (pDA) modifications strengthened the scaffold bioactivity. Gelatin microspheres (GMs) protected the pharmacological activity of DFO, achieving local application and sustained release for seven days. DFO effectively promoted angiogenesis by activating the signaling pathway of hypoxia inducible factor‐1 α (HIF‐1 α). In addition, DFO synergized with HNTs to promote osteogenic differentiation and matrix mineralization. These results indicated that DGPN promoted bone regeneration and accelerated cranial defect healing.This article is protected by copyright. All rights reserved

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Molecular Processes in Chondrocyte Biology

Abstract: Chondrocyte biology is a hot topic, because osteoarthritis (OA) is a serious problem in an aging society, but there are no fundamental therapeutic drugs [...]

Cited by 7 publications

References 17 publications

Extracellular Vesicle-Mediated miR-150-3p Delivery in Joint Homeostasis: A Potential Treatment for Osteoarthritis?

Extracellular Vesicle-Mediated miR-150-3p Delivery in Joint Homeostasis: A Potential Treatment for Osteoarthritis?

Development of Nanomaterials to Target Articular Cartilage for Osteoarthritis Therapy

Hierarchical Composite Scaffold with Deferoxamine Delivery System to Promote Bone Regeneration via Optimizing Angiogenesis

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