Topographical cues of direct metal laser sintering titanium surfaces facilitate osteogenic differentiation of bone marrow mesenchymal stem cells through epigenetic regulation

Zheng, Gen; Guan, Binbin; Hu, Penghui; Qi, Xu; Wang, Pingting; Kong, Yu; Liu, Zihao; Gao, Ping; Li, Rui; Zhang, Xu; Wu, Xudong; Sui, Lei

doi:10.1111/cpr.12460

Cited by 25 publications

(28 citation statements)

References 55 publications

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“…In these cases, selective localization of Ash1l may coordinately modify local H3K4 methylation kinetics in the region of gene promoters. Including Ash1l, the overall 11 kinds of H3K4 methyltransferases [50] may coordinately promote H3K4me3 enrichment at osteogenic genes in tune during osteogenic differentiation [51]. It is reported that Ash1l and Mll1 cooperate to methylate H3K4 at actively transcribed region [15,52].…”

Section: Discussionmentioning

confidence: 99%

Epigenetic Control of Mesenchymal Stem Cell Fate Decision via Histone Methyltransferase Ash1l

Yin

Wang

et al. 2018

Stem Cells

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Previous research indicates that knocking out absent, small, or homeotic-like (Ash1l) in mice, a histone 3 lysine 4 (H3K4) trimethyltransferase, can result in arthritis with more severe cartilage and bone destruction. Research has documented the essential role of Ash1l in stem cell fate decision such as hematopoietic stem cells and the progenitors of keratinocytes. Following up on those insights, our research seeks to document the function of Ash1l in skeletal formation, specifically whether it controls the fate decision of mesenchymal progenitor cells. Our findings indicate that in osteoporotic bones, Ash1l was significantly decreased, indicating a positive correlation between bone mass and the expression of Ash1l. Silencing of Ash1l that had been markedly upregulated in differentiated C3H10T1/2 (C3) cells hampered osteogenesis and chondrogenesis but promoted adipogenesis. Consistently, overexpression of an Ash1l SET domain-containing fragment 3 rather than Ash1lΔN promoted osteogenic and chondrogenic differentiation of C3 cells and simultaneously inhibited adipogenic differentiation. This indicates that the role of Ash1l in regulating the differentiation of C3 cells is linked to its histone methyltransferase activity. Subcutaneous ex vivo transplantation experiments confirmed the role of Ash1l in the promotion of osteogenesis. Further experiments proved that Ash1l can epigenetically affect the expression of essential osteogenic and chondrogenic transcription factors. It exerts this impact via modifications in the enrichment of H3K4me3 on their promoter regions. Considering the promotional action of Ash1l on bone, it could potentially prompt new therapeutic strategy to promote osteogenesis. STEM CELLS 2019; 37:115-127 SIGNIFICANCE STATEMENTThe authors' research first discovered that Ash1l can epigenetically affect the expression of essential osteogenic and chondrogenic transcription factors via modifications in the enrichment of H3K4me3 on their promoter regions. These findings helped to further understand the role of Ash1l in the epigenetic regulation of C3H10T1/2 MSCs differentiation, which also makes it potential therapeutic target of bone diseases. Considering the promotional action of Ash1l on bone, it could potentially prompt new therapeutic strategy to promote osteogenesis.

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Section: Discussionmentioning

confidence: 99%

Epigenetic Control of Mesenchymal Stem Cell Fate Decision via Histone Methyltransferase Ash1l

Yin

Wang

et al. 2018

Stem Cells

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“…To mimic this environment, it is also of great significance to manufacture intraosseous implants with hierarchical micro-nano surface topography (Shah et al, 2018;Cui et al, 2019;Zhang et al, 2019). In our previous work, we fabricated titanium surfaces with hierarchical microprotrusionnanonotch topography using direct metal laser sintering technique together with acid etching treatment, which could promote osteogenic differentiation of stem cells (Zheng et al, 2018). To enable further performance improvements, hierarchical microgroove-nanopore topography was fabricated by selective laser melting (SLM) technique combined with alkali heat treatment (AHT) because of higher fabricating efficiency and less consumption of raw materials.…”

Section: Introductionmentioning

confidence: 99%

Hierarchical Micro-Nano Topography Promotes Cell Adhesion and Osteogenic Differentiation via Integrin α2-PI3K-AKT Signaling Axis

Zheng

Tian

Gao

et al. 2020

Front. Bioeng. Biotechnol.

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Surface topography dictates important aspects of cell biological behaviors. In our study, hierarchical micro-nano topography (SLM-AHT) with micro-scale grooves and nano-scale pores was fabricated and compared with smooth topography (S) and irregular micro-scale topography (SLA) surfaces to investigate mechanism involved in cell-surface interactions. Integrin α2 had a higher expression level on SLM-AHT surface compared with S and SLA surfaces, and the expression levels of osteogenic markers icluding Runx2, Col1a1, and Ocn were concomitantly upregulated on SLM-AHT surface. Moreover, formation of mature focal adhesions were significantly enhanced in SLM-AHT group. Noticablely, silencing integrin α2 could wipe out the difference of osteogenic gene expression among surfaces with different topography, indicating a crucial role of integrin α2 in topography induced osteogenic differentiation. In addition, PI3K-AKT signaling was proved to be regulated by integrin α2 and consequently participate in this process. Taken together, our findings illustrated that integrin α2-PI3K-AKT signaling axis plays a key role in hierarchical micro-nano topography promoting cell adhesion and osteogenic differentiation.

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“…The component and hierarchical structure are the key issues need to be simulated when constructing the biomimetic material (Wegst et al, 2015;Wingender et al, 2016;Ling et al, 2018;Zheng et al, 2018). ACP was a critical component and abundant in woven bone besides collagen and nHA.…”

Section: Discussionmentioning

confidence: 99%

The Injectable Woven Bone-Like Hydrogel to Perform Alveolar Ridge Preservation With Adapted Remodeling Performance After Tooth Extraction

Xie

Liao

et al. 2020

Front. Bioeng. Biotechnol.

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Grafting bone substitute is paramount to prevent the alveolar ridge resorption after tooth extraction and facilitate the subsequent implant treatment. An ideal bone substitute should acquire the excellent osteogenic property, more importantly, possess the suitable remodeling rate in balance with bone formation and desirable clinical manageability. However, none of bone substitute is simultaneously characterized by these features, and currently, the limited remodeling property leads to the excessive waiting time before implantation. Enlightened by woven bone, the transitional tissue that is able to induce osteogenesis during bone healing could be easily remodeled within a short period and depend on the favorable injectability of hydrogel, an injectable woven bone-like hydrogel (IWBLH) was constructed in this study to address the above problems. To mimic the component and hierarchical structure of woven bone, amorphous calcium phosphate (ACP) and mineralized collagen fibril were synthesized and compounded with alginate to form IWBLHs with various ratio. Screened by physiochemical characterization and in vitro biological assays, an optimal IWBLH was selected and further explored in rat model of tooth extraction. Compared with the most widely used bone substitute, we showed that IWBLH could be easily handled to fully fill the tooth socket, perform a comparable function to prevent the alveolar bone resorption, and completely remodeled within 4 weeks. This IWBLH stands as a promising candidate for alveolar ridge preservation (ARP) in future.

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Topographical cues of direct metal laser sintering titanium surfaces facilitate osteogenic differentiation of bone marrow mesenchymal stem cells through epigenetic regulation

Cited by 25 publications

References 55 publications

Epigenetic Control of Mesenchymal Stem Cell Fate Decision via Histone Methyltransferase Ash1l

Epigenetic Control of Mesenchymal Stem Cell Fate Decision via Histone Methyltransferase Ash1l

Hierarchical Micro-Nano Topography Promotes Cell Adhesion and Osteogenic Differentiation via Integrin α2-PI3K-AKT Signaling Axis

The Injectable Woven Bone-Like Hydrogel to Perform Alveolar Ridge Preservation With Adapted Remodeling Performance After Tooth Extraction

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