miR-140-5p protects cartilage progenitor/stem cells from fate changes in knee osteoarthritis

Chen, Yang; Hua, Huang; Zhong, Wen; Li, Lan; Lu, Yanrong; Si, Haibo

doi:10.1016/j.intimp.2022.109576

Cited by 5 publications

(4 citation statements)

References 62 publications

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“…Many reports have shown that miRNAs carried by Exos secreted by stem cells can alleviate the progression of OA. [18,22,23] In clinical therapy, ADSCs are superior to other cells because of their lower immune rejection potential, abundant sources, safety and low cost. [8,9] In this study, we found that there were some differences in ECM synthesis and degradation between IPFP-and ScAT-derived Exos in the treatment of OA.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have demonstrated that miRNAs play a key role in mediating the effects of the main risk factors for OA through the control of target genes and are critical in the pathological process of OA. [22][23][24][25] Clinically, the IPFP is often routinely removed and disposed of as surgical waste during arthroscopy or open knee surgery, and most of it comes from elderly patients (who usually also have chronic diseases) with knee arthroplasty. [18,26] Therefore, it has higher expression of in ammatory genes, releases more in ammatory factors, and contains more immune cells than ScAT.…”

Section: Introductionmentioning

confidence: 99%

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Sustained released of microRNA-99b-3p abundant exosomes derived from adipose stem cell encapsulated with hydrogel microparticles (HMPs) for long-term osteoarthritis treatment

Yin¹,

Pan

Shi

et al. 2023

Preprint

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Adipose derived stem cells (ADSCs) have the potential to attenuate osteoarthritis (OA); however, complications such as immune rejection and tumour formation limit their application. Exosomes (Exos)-mediated acellular therapy is promising in alleviating OA. This study aims to confirm whether ADSC-exos derived from infrapatellar fat pad (IPFP, ExosIPFP) are more suitable for ameliorating OA than ADSC-exos derived from subcutaneous fat (ScAT, ExoScAT) in vitro and in DMM models. Then, we investigated the regulatory mechanism by which the two kinds of Exos inhibit extracellular matrix (ECM) degradation in OA. ADSCs were successfully isolated and Exos were then obtained. ExosIPFP exhibited better attenuated effects on osteoarthritic chondrocytes in vitro and in vivo than ExoScAT. Small RNA sequencing was performed and the results shown that miR-99b-3p was upregulated in ExosIPFP. In vitro experiments confirmed that ADAMTS4 is a direct downstream target of miR-99b-3p. Over-expression miR-99b-3p in ExosScAT (ExosScAT-99b-3p) indicated that miR-99b-3p serves a positive role for OA treatment by inhibiting ADAMTS4 expression both in vitro and in vivo. In addition, hydrogel microparticles (HMPs) system was prepared by microfluidic technology, and confirmed the beneficial results for long-term therapeutic by continuous release of Exos. Take together, these results suggest that the therapeutic effects of ADSC-Exos may vary according to differential expression of miRNAs. Exosomal miR-99b-3p may act as a promising therapeutic strategy for OA, in addition, the injectable HMPs act as a sustained local drug release system, therefore representing great potential for treating OA and other diseases.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Sustained released of microRNA-99b-3p abundant exosomes derived from adipose stem cell encapsulated with hydrogel microparticles (HMPs) for long-term osteoarthritis treatment

Yin¹,

Pan

Shi

et al. 2023

Preprint

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show abstract

“…Moreover, Exos contain many functional miRNAs, and miRNAs have the ability to modulate the expression of multiple genes implicated in various kinds of physiological functions and disease processes, such as OA. Previous studies have demonstrated that miRNAs play a key role in mediating the effects of the main risk factors for OA through the control of target genes and are critical in the pathological process of OA [ [23] , [24] , [25] , [26] ].…”

Section: Introductionmentioning

confidence: 99%

Injectable hyperbranched PEG crosslinked hyaluronan hydrogel microparticles containing mir-99a-3p modified subcutaneous ADSCs-derived exosomes was beneficial for long-term treatment of osteoarthritis

Yin,

Qin,

Pan

et al. 2023

Materials Today Bio

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“…miR-140 is one of the most important miRNAs in cartilage. Expression of miR-140 was reduced in cartilage progenitors/stem cells derived from OA cartilage, whereas miR-140 mimics alleviated OA-like changes in these stem cells [ 20 ]. Treatment of chondrocytes with exosomes overexpressing miR-140 resulted in increased secretion of extracellular matrix components, such as collagen and aggrecan, and in addition, intra-articular injection of these exosomes resulted in increased cartilage regeneration in an OA rat model [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA Signatures in Cartilage Ageing and Osteoarthritis

et al. 2023

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Osteoarthritis is the most common degenerative joint disorder. MicroRNAs are gene expression regulators that act post-transcriptionally to control tissue homeostasis. Microarray analysis was undertaken in osteoarthritic intact, lesioned and young intact cartilage. Principal component analysis showed that young intact cartilage samples were clustered together; osteoarthritic samples had a wider distribution; and osteoarthritic intact samples were separated into two subgroups, osteoarthritic-Intact-1 and osteoarthritic-Intact-2. We identified 318 differentially expressed microRNAs between young intact and osteoarthritic lesioned cartilage, 477 between young intact and osteoarthritic-Intact-1 cartilage and 332 between young intact and osteoarthritic-Intact-2 cartilage samples. For a selected list of differentially expressed microRNAs, results were verified in additional cartilage samples using qPCR. Of the validated DE microRNAs, four—miR-107, miR-143-3p, miR-361-5p and miR-379-5p—were selected for further experiments in human primary chondrocytes treated with IL-1β. Expression of these microRNAs decreased in human primary chondrocytes treated with IL-1β. For miR-107 and miR-143-3p, gain- and loss-of-function approaches were undertaken and associated target genes and molecular pathways were investigated using qPCR and mass spectrometry proteomics. Analyses showed that WNT4 and IHH, predicted targets of miR-107, had increased expression in osteoarthritic cartilage compared to young intact cartilage and in primary chondrocytes treated with miR-107 inhibitor, and decreased expression in primary chondrocytes treated with miR-107 mimic, suggesting a role of miR-107 in chondrocyte survival and proliferation. In addition, we identified an association between miR-143-3p and EIF2 signalling and cell survival. Our work supports the role of miR-107 and miR-143-3p in important chondrocyte mechanisms regulating proliferation, hypertrophy and protein translation.

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miR-140-5p protects cartilage progenitor/stem cells from fate changes in knee osteoarthritis

Cited by 5 publications

References 62 publications

Sustained released of microRNA-99b-3p abundant exosomes derived from adipose stem cell encapsulated with hydrogel microparticles (HMPs) for long-term osteoarthritis treatment

Sustained released of microRNA-99b-3p abundant exosomes derived from adipose stem cell encapsulated with hydrogel microparticles (HMPs) for long-term osteoarthritis treatment

Injectable hyperbranched PEG crosslinked hyaluronan hydrogel microparticles containing mir-99a-3p modified subcutaneous ADSCs-derived exosomes was beneficial for long-term treatment of osteoarthritis

MicroRNA Signatures in Cartilage Ageing and Osteoarthritis

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