Dataset Information

A lithium-containing biomaterial promotes chondrogenic differentiation of induced pluripotent stem cells with reducing hypertrophy.

ABSTRACT:

Background

Induced pluripotent stem cells (iPSCs) exhibit limitless pluripotent plasticity and proliferation capability to provide an abundant cell source for tissue regenerative medicine. Thus, inducing iPSCs toward a specific differentiation direction is an important scientific question. Traditionally, iPSCs have been induced to chondrocytes with the help of some small molecules within 21-36?days. To speed up the differentiation of iPSCs, we supposed to utilize bioactive ceramics to assist chondrogenic-induction process.

Methods

In this study, we applied ionic products (3.125~12.5?mg/mL) of the lithium-containing bioceramic (Li₂Ca₄Si₄O₁₃, L2C4S4) and individual Li⁺ (5.78~23.73?mg/L) in the direct chondrogenic differentiation of human iPSCs.

Results

Compared to pure chondrogenic medium and extracts of tricalcium phosphate (TCP), the extracts of L2C4S4 at a certain concentration range (3.125~12.5?mg/mL) significantly enhanced chondrogenic proteins Type II Collagen (COL II)/Aggrecan/ SRY-Box 9 (SOX9) synthesis and reduced hypertrophic protein type X collagen (COL X)/matrix metallopeptidase 13 (MMP13) production in iPSCs-derived chondrocytes within 14?days, suggesting that these newly generated chondrocytes exhibited favorable chondrocytes characteristics and maintained a low-hypertrophy state. Further studies demonstrated that the individual Li⁺ ions at the concentration range of 5.78~23.73?mg/L also accelerated the chondrogenic differentiation of iPSCs, indicating that Li⁺ ions played a pivotal role in chondrogenic differentiation process.

Conclusions

These findings indicated that lithium-containing bioceramic with bioactive specific ionic components may be used for a promising platform for inducing iPSCs toward chondrogenic differentiation and cartilage regeneration.

SUBMITTER: Hu Y

PROVIDER: S-EPMC7035784 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Publications

A lithium-containing biomaterial promotes chondrogenic differentiation of induced pluripotent stem cells with reducing hypertrophy.

Hu Yaqian Y Chen Lei L Gao Yi Y Cheng Pengzhen P Yang Liu L Wu Chengtie C Jie Qiang Q

Stem cell research & therapy 20200221 1

<h4>Background</h4>Induced pluripotent stem cells (iPSCs) exhibit limitless pluripotent plasticity and proliferation capability to provide an abundant cell source for tissue regenerative medicine. Thus, inducing iPSCs toward a specific differentiation direction is an important scientific question. Traditionally, iPSCs have been induced to chondrocytes with the help of some small molecules within 21-36 days. To speed up the differentiation of iPSCs, we supposed to utilize bioactive ceramics to as ...[more]

PMID: 32085810

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Project description:Background and objectivesOsteoarthritis (OA) is a degenerative disease that leads to the progressive destruction of articular cartilage. Current clinical therapeutic strategies are moderately effective at relieving OA-associated pain but cannot induce chondrocyte differentiation or achieve cartilage regeneration. We investigated the ability of wedelolactone, a biologically active natural product that occurs in Eclipta alba (false daisy), to promote chondrogenic differentiation.Methods and resultsReal-time reverse transcription-polymerase chain reaction, immunohistochemical staining, and immunofluorescence staining assays were used to evaluate the effects of wedelolactone on the chondrogenic differentiation of mesenchymal stem cells (MSCs). RNA sequencing, microRNA (miRNA) sequencing, and isobaric tags for relative and absolute quantitation analyses were performed to explore the mechanism by which wedelolactone promotes the chondrogenic differentiation of MSCs. We found that wedelolactone facilitates the chondrogenic differentiation of human induced pluripotent stem cell-derived MSCs and rat bone-marrow MSCs. Moreover, the forkhead box O (FOXO) signaling pathway was upregulated by wedelolactone during chondrogenic differentiation, and a FOXO1 inhibitor attenuated the effect of wedelolactone on chondrocyte differentiation. We determined that wedelolactone reduces enhancer of zeste homolog 2 (EZH2)-mediated histone H3 lysine 27 trimethylation of the promoter region of FOXO1 to upregulate its transcription. Additionally, we found that wedelolactone represses miR-1271-5p expression, and that miR-1271-5p post-transcriptionally suppresses the expression of FOXO1 that is dependent on the binding of miR-1271-5p to the FOXO1 3'-untranscribed region.ConclusionsThese results indicate that wedelolactone suppresses the activity of EZH2 to facilitate the chondrogenic differentiation of MSCs by activating the FOXO1 signaling pathway. Wedelolactone may therefore improve cartilage regeneration in diseases characterized by inflammatory tissue destruction, such as OA.

Dataset Information

A lithium-containing biomaterial promotes chondrogenic differentiation of induced pluripotent stem cells with reducing hypertrophy.

Background

Methods

Results

Conclusions

Publications

A lithium-containing biomaterial promotes chondrogenic differentiation of induced pluripotent stem cells with reducing hypertrophy.

Similar Datasets

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