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Mouse bone marrow mesenchymal stem cells with distinct p53 statuses display differential characteristics.

ABSTRACT: Mesenchymal stem cells (MSCs) affect diverse aspects of tumor progression, such as angiogenesis, tumor growth and metastasis. Bone marrow MSCs (BM?MSCs) are fibroblast?like cells with multipotent differentiation ability, that localize to areas of tissue damage, including wounds and solid tumors. The tumor suppressor gene, p53, is functionally involved in cell cycle control, apoptosis and genomic stability, and is mutated and inactivated in most human cancers. The present study aimed to investigate the role of p53 in the biology of BM?MSCs. In the present study, p53 wild?type (p53+/+), knockdown (p53+/?) and knockout (p53?/?) mouse BM?MSCs (mBM?MSCs) were observed to be similar in appearance and in the expression of cell surface biomarkers, but expressed differential p53 protein levels. The p53+/? and p53?/? mBM?MSCs demonstrated an increased proliferation rate compared with mBM?MSCs derived from p53+/+ mice. mBM?MSCs from all three groups, representing distinct p53 statuses, were unable to form tumors over a 3?month period in vivo. The adipogenic and osteogenic differentiation of mBM?MSCs was increased in the absence of p53. The colony formation and migratory abilities of p53+/? and p53?/? mBM?MSCs were markedly enhanced, and the expression levels of stem cell?associated proteins were significantly increased compared with p53+/+. The expression levels of microRNA (miR)?3152 and miR?337 were significantly increased in p53+/? and p53?/? mBM?MSCs, whereas the expression levels of miR?221, miR?155, miR?1288 and miR?4669 were significantly decreased. The expression levels of tumor necrosis factor?? and interferon???inducible protein?10 were significantly upregulated in the supernatant of p53+/? and p53?/? mBM?MSCs. Ubiquitin protein ligase E3 component n?recognin 2, RING?finger protein 31 and matrix metalloproteinase 19 were highly expressed in p53+/? and p53?/? mBM?MSCs. The results of the present study indicated that p53 may serve an important role in the biology of mBM?MSCs, and may provide novel insights into the role of cells with different p53 statuses in cancer progression.

SUBMITTER: Wang B

PROVIDER: S-EPMC7115213 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Mouse bone marrow mesenchymal stem cells with distinct p53 statuses display differential characteristics.

Wang Bo B Wang Lingxia L Mao Jiahui J Wen Huiyan H Xu Longjiang L Ren Yang Y Du Hong H Yang Huan H

Molecular medicine reports 20200312 5

Mesenchymal stem cells (MSCs) affect diverse aspects of tumor progression, such as angiogenesis, tumor growth and metastasis. Bone marrow MSCs (BM‑MSCs) are fibroblast‑like cells with multipotent differentiation ability, that localize to areas of tissue damage, including wounds and solid tumors. The tumor suppressor gene, p53, is functionally involved in cell cycle control, apoptosis and genomic stability, and is mutated and inactivated in most human cancers. The present study aimed to investiga ...[more]

PMID: 32186775

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Project description:Long bone is an anatomically complicated tissue with trabecular-rich metaphyses at two ends and cortical-rich diaphysis at the center. The traditional flushing method isolates only mesenchymal progenitor cells from the central region of long bones and these cells are distant from the bone surface. We propose that mesenchymal progenitors residing in endosteal bone marrow that is close to the sites of bone formation, such as trabecular bone and endosteum, behave differently from those in the central bone marrow. In this report, we separately isolated endosteal bone marrow using a unique enzymatic digestion approach and demonstrated that it contained a much higher frequency of mesenchymal progenitors than the central bone marrow. Endosteal mesenchymal progenitors express common mesenchymal stem cell markers and are capable of multi-lineage differentiation. However, we found that mesenchymal progenitors isolated from different anatomical regions of the marrow did exhibit important functional differences. Compared with their central marrow counterparts, endosteal mesenchymal progenitors have superior proliferative ability with reduced expression of cell cycle inhibitors. They showed greater immunosuppressive activity in culture and in a mouse model of inflammatory bowel disease. Aging is a major contributing factor for trabecular bone loss. We found that old mice have a dramatically decreased number of endosteal mesenchymal progenitors compared with young mice. Parathyroid hormone (PTH) treatment potently stimulates bone formation. A single PTH injection greatly increased the number of endosteal mesenchymal progenitors, particularly those located at the metaphyseal bone, but had no effect on their central counterparts. In summary, endosteal mesenchymal progenitors are more metabolically active and relevant to physiological bone formation than central mesenchymal progenitors. Hence, they represent a biologically important target for future mesenchymal stem cell studies.

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Mouse bone marrow mesenchymal stem cells with distinct p53 statuses display differential characteristics.

Publications

Mouse bone marrow mesenchymal stem cells with distinct p53 statuses display differential characteristics.

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