Suppression of ornithine decarboxylase promotes osteogenic differentiation of human bone marrow‐derived mesenchymal stem cells

Tsai, Yo-Hsian; Lin, Kuan-Lian; Huang, Yuanyuan; Hsu, Yi‐Chiang; Ch, Chen; Chen, Yu‐Hsin; Sie, Min-Hua; Wang, Gwo-Jaw; Lee, Mon-Juan

doi:10.1016/j.febslet.2015.06.023

Cited by 17 publications

(20 citation statements)

References 33 publications

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“…Adipose droplets were subjected to Oil Red O staining. For osteogenic differentiation (51)(52)(53)(54), MSC cultures were expanded by treatment with osteogenic induction medium (low-sugar DMEM supplemented with 10% FBS, 100 nM dexamethasone, 0.2 mM ascorbic acid, and 10 mM b-glycerophosphate). Cells were maintained by the addition of fresh osteogenic induction medium every 2-3 d. For chondrogenic differentiation (55), cells were cultured in chondrogenic induction medium [high-glucose DMEM, 40 mg/ml proline, 100 nM dexamethasone, 50 ng/ml ascorbic acid-2-phosphate, ITS-X (insulin, transferrin, selenium, ethanolamine solution), and 10 ng/ml TGF-b3] for 21 d. Sulfated glycosaminoglycans were stained with Alcian Blue (Cyagen Biosciences, Guangzhou, China).…”

Section: Bmsc Isolation Culture Identification and Differentiationmentioning

confidence: 99%

IGFBP7 regulates the osteogenic differentiation of bone marrow‐derived mesenchymal stem cellsviaWnt/β‐catenin signaling pathway

Zhang

Chen

et al. 2018

FASEB j.

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Insulin-like growth factor-binding protein 7 (IGFBP7), a low-affinity IGF binder, may play an important role in bone metabolism. However, its function in osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (BMSCs) remains unclear. Therefore, we investigated its effects on osteogenic differentiation. Overexpression of IGFBP7 enhanced the expression of osteo-specific genes and proteins, and IGFBP7 knockdown decreased osteogenesis-specific markers. More mineral deposits and higher alkaline phosphatase activity were observed after the up-regulation of IGFBP7. Moreover, β-catenin levels were up-regulated by the overexpression of IGFBP7 or the addition of extracellular IGFBP7 protein and were reduced by the depletion of IGFBP7. The increase in osteogenic differentiation due to the overexpression of IGFBP7 was partially decreased by specific Wnt/β-catenin signaling inhibitors. Using a rat tibial osteotomy model, a sheet of IGFBP7-overexpressing BMSCs improved bone healing, as demonstrated by imaging, biomechanical, and histologic analyses. Taken together, these findings indicate that IGFBP7 regulates the osteogenic differentiation of BMSCs partly via the Wnt/β-catenin signaling pathway.-Zhang, W., Chen, E., Chen, M., Ye, C., Qi, Y., Ding, Q., Li, H., Xue, D., Gao, X., Pan, Z. IGFBP7 regulates the osteogenic differentiation of bone marrow-derived mesenchymal stem cells via Wnt/β-catenin signaling pathway.

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Section: Bmsc Isolation Culture Identification and Differentiationmentioning

confidence: 99%

IGFBP7 regulates the osteogenic differentiation of bone marrow‐derived mesenchymal stem cellsviaWnt/β‐catenin signaling pathway

Zhang

Chen

et al. 2018

FASEB j.

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“…23 Proliferation assays were performed as described below with cells in regular medium and cells with DFMO.…”

Section: Dfmo Treatmentmentioning

confidence: 99%

Ornithine Decarboxylase Is Sufficient for Prostate Tumorigenesis via Androgen Receptor Signaling

Shukla–Dave

Castillo-Martín

Chen

et al. 2016

The American Journal of Pathology

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Increased polyamine synthesis is known to play an important role in prostate cancer. We aimed to explore its functional significance in prostate tumor initiation and its link to androgen receptor (AR) signaling. For this purpose, we generated a new cell line derived from normal epithelial prostate cells (RWPE-1) with overexpression of ornithine decarboxylase (ODC) and used it for in vitro and in vivo experiments. We then comprehensively analyzed the expression of the main metabolic enzymes of the polyamine pathway and spermine abundance in 120 well-characterized cases of human prostate cancer and high-grade prostate intraepithelial neoplasia (HGPIN). Herein, we show that the ODCoverexpressing prostate cells underwent malignant transformation, revealing that ODC is sufficient for de novo tumor initiation in 94% of injected mice. This oncogenic capacity was acquired through alteration of critical signaling networks, including AR, EIF2, and mTOR/MAPK. RNA silencing experiments revealed the link between AR signaling and polyamine metabolism. Human prostate cancers consistently demonstrated up-regulation of the main polyamine enzymes analyzed (ODC, polyamine oxidase, and spermine synthase) and reduction of spermine. This phenotype was also dominant in HGPIN, rendering it a new biomarker of malignant transformation. In summary, we report that ODC plays a key role in prostate tumorigenesis and that the polyamine pathway is altered as early as HGPIN. (Am J Pathol 2016, 186: 3131e3145; http://dx

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“…Ornithine decarboxylase (ODC) and polyamine biosynthesis are important in the proliferation of stem cells (Tsai et al, 2015). The role of ODC regarding differentiation has not been fully explored but is considered to be diverse.…”

Section: Metabolism Of Mscs Msc Function Is Linked To Metabolismmentioning

confidence: 99%

“…The role of ODC regarding differentiation has not been fully explored but is considered to be diverse. Through the study of inhibition of ODC's irreversible inhibitor, α-difluoromethylornithine, Tsai et al (2015) hypothesized that inhibition of ODC and the accompanying depletion of exogenous polyamines might be correlated with the osteogenic induction of BM-hMSCs, and demonstrated (in BM-hMSCs) that decreases in the expression of PPAR-γ and ODC along with an accompanying reduction in polyamines, are responsible for enhanced osteogenesis.…”

Section: Metabolism Of Mscs Msc Function Is Linked To Metabolismmentioning

confidence: 99%

Current Status and Future Prospects of Genome-Scale Metabolic Modeling to Optimize the Use of Mesenchymal Stem Cells in Regenerative Medicine

Sigmarsdóttir

McGarrity

Rolfsson

et al. 2020

Front. Bioeng. Biotechnol.

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Mesenchymal stem cells are a promising source for externally grown tissue replacements and patient-specific immunomodulatory treatments. This promise has not yet been fulfilled in part due to production scaling issues and the need to maintain the correct phenotype after re-implantation. One aspect of extracorporeal growth that may be manipulated to optimize cell growth and differentiation is metabolism. The metabolism of MSCs changes during and in response to differentiation and immunomodulatory changes. MSC metabolism may be linked to functional differences but how this occurs and influences MSC function remains unclear. Understanding how MSC metabolism relates to cell function is however important as metabolite availability and environmental circumstances in the body may affect the success of implantation. Genome-scale constraint based metabolic modeling can be used as a tool to fill gaps in knowledge of MSC metabolism, acting as a framework to integrate and understand various data types (e.g., genomic, transcriptomic and metabolomic). These approaches have long been used to optimize the growth and productivity of bacterial production systems and are being increasingly used to provide insights into human health research. Production of tissue for implantation using MSCs requires both optimized production of cell mass and the understanding of the patient and phenotype specific metabolic situation. This review considers the current knowledge of MSC metabolism and how it may be optimized along with the current and future uses of genome scale constraint based metabolic modeling to further this aim.

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Suppression of ornithine decarboxylase promotes osteogenic differentiation of human bone marrow‐derived mesenchymal stem cells

Cited by 17 publications

References 33 publications

IGFBP7 regulates the osteogenic differentiation of bone marrow‐derived mesenchymal stem cellsviaWnt/β‐catenin signaling pathway

IGFBP7 regulates the osteogenic differentiation of bone marrow‐derived mesenchymal stem cellsviaWnt/β‐catenin signaling pathway

Ornithine Decarboxylase Is Sufficient for Prostate Tumorigenesis via Androgen Receptor Signaling

Current Status and Future Prospects of Genome-Scale Metabolic Modeling to Optimize the Use of Mesenchymal Stem Cells in Regenerative Medicine

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