After repeated division, bone marrow stromal cells express inhibitory factors with osteogenic capabilities, and EphA5 is a primary candidate

Bone
Tsuyoshi YamadaShinichi Sotome

Abstract

The differentiation capability of human bone marrow stromal cells (hBMSCs) is thought to deteriorate over multiple doubling processes. To clarify the deterioration mechanisms, the multilineage differentiation capabilities of short- and long-term passaged BMSCs were compared. Predictably, long-term passaged BMSCs showed reduced differentiation capacities compared to short-term passaged cells. Furthermore, a non-human primate heterotopic bone formation model demonstrated that long-term passaged BMSCs have bone formation capabilities but also exert inhibitory effects on bone formation. This finding indicated that long-term passaged BMSCs express higher levels of inhibitory factors than short-term passaged BMSCs do. Co-culture assays of short- and long-term passaged BMSCs suggested that the inhibitory signals required cell-cell contact and would therefore be expressed on the cell membrane. A microarray analysis of BMSCs identified ephrin type-A receptor 5 (EphA5) as an inhibitory factor candidate. Quantitative PCR revealed that among all members of the ephrin and Eph receptor families, only the expression of EphA5 was increased by BMSC proliferation. A gene knockdown analysis using siRNAs demonstrated that knockdown of EphA5 gene e...Continue Reading

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Citations

Mar 28, 2018·Journal of Molecular Endocrinology·Richard C LindseySubburaman Mohan
Mar 29, 2019·PloS One·Yasuhisa YoshidaHiroyuki Tsuchiya
Apr 24, 2020·Molecular Medicine Reports·Faxiang WangZhujuan Zhou
Dec 9, 2020·International Journal of Molecular Sciences·Jolanta SzenajchLuiza Handschuh
Feb 27, 2021·Frontiers in Cell and Developmental Biology·Agnieszka Arthur, Stan Gronthos

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