Silencing of SPARC represses heterotopic ossification via inhibition of the MAPK signaling pathway

Wang, Qianjun; Yang, Qianqian; Zhang, Ali; Kang, Zhiqiang; Wang, Yingsheng; Zhang, Zhentao

doi:10.1042/bsr20191805

Cited by 19 publications

(21 citation statements)

References 35 publications

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“…We found that while SPARC expression can be induced by TGF-β in normal lung fibroblasts, it is aberrantly expressed by IPFFs and that it acts via a paracrine mechanism to mediate RAS activation in ATII cells. SPARC has been shown by several studies to be able to regulate ERK signaling ( 35 , 36 , 37 ), although the upstream mechanism remains to be elucidated. In this study, our results demonstrated that SPARC alone is sufficient to induce EGFR activation in ATII cells, suggesting that SPARC might signal via the EGFR similar to tenascin C ( 38 , 39 , 40 ) via their epithelial growth factor–like repeats ( 41 ).…”

Section: Discussionmentioning

confidence: 99%

Bidirectional epithelial–mesenchymal crosstalk provides self-sustaining profibrotic signals in pulmonary fibrosis

Yao

Zhou

et al. 2021

Journal of Biological Chemistry

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Idiopathic pulmonary fibrosis (IPF) is the prototypic progressive fibrotic lung disease with a median survival of 2 to 4 years. Injury to and/or dysfunction of the alveolar epithelium is strongly implicated in IPF disease initiation, but the factors that determine whether fibrosis progresses rather than normal tissue repair occurs remain poorly understood. We previously demonstrated that zinc finger E-box-binding homeobox 1–mediated epithelial–mesenchymal transition in human alveolar epithelial type II (ATII) cells augments transforming growth factor-β–induced profibrogenic responses in underlying lung fibroblasts via paracrine signaling. Here, we investigated bidirectional epithelial–mesenchymal crosstalk and its potential to drive fibrosis progression. RNA-Seq of lung fibroblasts exposed to conditioned media from ATII cells undergoing RAS-induced epithelial–mesenchymal transition identified many differentially expressed genes including those involved in cell migration and extracellular matrix regulation. We confirmed that paracrine signaling between RAS-activated ATII cells and fibroblasts augmented fibroblast recruitment and demonstrated that this involved a zinc finger E-box-binding homeobox 1–tissue plasminogen activator axis. In a reciprocal fashion, paracrine signaling from transforming growth factor-β–activated lung fibroblasts or IPF fibroblasts induced RAS activation in ATII cells, at least partially through the secreted protein acidic and rich in cysteine, which may signal via the epithelial growth factor receptor via epithelial growth factor–like repeats. Together, these data identify that aberrant bidirectional epithelial–mesenchymal crosstalk in IPF drives a chronic feedback loop that maintains a wound-healing phenotype and provides self-sustaining profibrotic signals.

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Section: Discussionmentioning

confidence: 99%

Bidirectional epithelial–mesenchymal crosstalk provides self-sustaining profibrotic signals in pulmonary fibrosis

Yao

Zhou

et al. 2021

Journal of Biological Chemistry

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“…The MAPK pathway including ERK, JNK and p38 pathways, is involved in inflammatory signaling, regulation of cell proliferation and differentiation, and activation of the immune system ( Lai et al, 2020 ). The ERK1/2, JNK, and p38 pathways regulate osteoblast differentiation ( Chen et al, 2016 ), and inhibition of MAPK signaling was shown to reduce the expression levels of ALP and OCN ( Wang et al, 2019 ). JNK is a downstream effector of the proinflammatory cytokine-induced immune response in AS.…”

Section: Discussionmentioning

confidence: 99%

Anti-Osteogenic Effect of Danshensu in Ankylosing Spondylitis: An in Vitro Study Based on Integrated Network Pharmacology

Chen

Liao

et al. 2021

Front. Pharmacol.

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Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by abnormal bone metabolism, with few effective treatments available. Danshensu [3-(3,4-dihydroxy-phenyl) lactic acid) is a bioactive compound from traditional Chinese medicine with a variety of pharmacologic effects. In the present study, we investigated the pharmacologic effect and molecular mechanism of Danshensu in AS. Potential targets of Danshensu were identified in four drugs-genes databases; and potential pharmacologic target genes in AS were identified in three diseases-genes databases. Differentially expressed genes related to AS were obtained from the Gene Expression Omnibus database. Overlapping targets of Danshensu and AS were determined and a disease–active ingredient–target interaction network was constructed with Cytoscape software. Enrichment analyses of the common targets were performed using Bioconductor. To test the validity of the constructed network, an in vitro model was established by treating osteoblasts from newborn rats with low concentrations of tumor necrosis factor (TNF)-α. Then, the in vitro model and AS fibroblasts were treated with Danshensu (1–10 μM). Osteogenesis was evaluated by alkaline phosphatase staining and activity assay, alizarin red staining, quantitative PCR, and western blotting. We identified 2944 AS-related genes and 406 Danshensu targets, including 47 that were common to both datasets. The main signaling pathways associated with the targets were the c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) pathways. A low concentration of TNF-α (0.01 ng/ml) promoted the differentiation of osteoblasts; this was inhibited by Danshensu, which had the same effect on AS fibroblasts but had the opposite effect on normal osteoblasts. Danshensu also decreased the phosphorylation of JNK and ERK in AS fibroblasts. There results provide evidence that Danshensu exerts an anti-osteogenic effect via suppression of JNK and ERK signaling, highlighting its therapeutic potential for the treatment of AS.

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“…OPN and BSP are symbols of the advanced stage of osteogenic differentiation, and indicate the differentiation and maturation of bone 44‐50 . Osteonectin (ON) can promote the viability, differentiation and matrix mineralization ofosteoblasts 51‐54 . As non‐collagenous extracellular matrix proteins, they play vital role in osteoblast differentiation and bone formation.…”

Section: Discussionmentioning

confidence: 99%

Different grinding speeds affect induced regeneration capacity of human treated dentin matrix

Yang

Song

et al. 2021

J Biomed Mater Res

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Human-treated dentin matrix (hTDM) is a biomaterial scaffold, which can induce implant cells to differentiate into odontoblasts and then form neo-dentin. However, hTDM with long storage or prepared by high-speed handpiece would not to form neo-dentin. In this research, we developed two fresh hTDM with different grinding speeds, which were low-speed hTDM (LTDM) with maximum speed of 500 rpm and high-speed hTDM (HTDM) with a speed of 3,80,000 rpm. Here, we aim to understand whether there were induced regeneration capacity differences between LTDM and HTDM. Scanning electron microscope showed that DFCs grew well on both materials, but the morphology of DFCs and the extracellular matrix was different.Especially, the secreted extracellular matrixes on the inner surface of LTDM were regular morphology and ordered arrangement around the dentin tubules. The transcription-quantitative polymerase chain reaction (qRT-PCR), western blot and immunofluorescence assay showed that the dentin markers DSPP and DMP-1 were about 2Â greater in DFCs induced by LTDM than by HTDM, and osteogenic marker BSP was about 2Â greater in DFCs induced by HTDM than by LTDM. Histological examinations of the harvested grafts observed the formation of neo-tissue were different, and there were neo-dentin formed on the inner surface of LTDM and neocementum formed on the outer surface of HTDM. In summary, it found that the induction abilities of LTDM and HTDM are different, and the dentin matrix is directional. This study lays a necessary foundation for searching the key factors of dentin regeneration in future.high-speed human-treated dentin matrix, induced regeneration capacity, low-speed humantreated dentin matrix, odontogenic differentiation, osteogenic differentiation | INTRODUCTIONBiological scaffolds are currently the most popular scaffold in tissue engineering. [1][2][3] The specific three-dimensional structure, the distinctive extracellular matrix and the most active proteins retained in the Min Li and Sen Yang have contributed equally to this study.

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Silencing of SPARC represses heterotopic ossification via inhibition of the MAPK signaling pathway

Cited by 19 publications

References 35 publications

Bidirectional epithelial–mesenchymal crosstalk provides self-sustaining profibrotic signals in pulmonary fibrosis

Bidirectional epithelial–mesenchymal crosstalk provides self-sustaining profibrotic signals in pulmonary fibrosis

Anti-Osteogenic Effect of Danshensu in Ankylosing Spondylitis: An in Vitro Study Based on Integrated Network Pharmacology

Different grinding speeds affect induced regeneration capacity of human treated dentin matrix

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