PCBP2 as an intrinsic aging factor regulates the senescence of hBMSCs through the ROS-FGF2 signaling axis

  1. Pengbo Chen
  2. Bo Li
  3. Zeyu Lu
  4. Qingyin Xu
  5. Huoliang Zheng
  6. Shengdan Jiang
  7. Leisheng Jiang
  8. Xinfeng Zheng

  • Curated by eLife

    eLife logo

    eLife assessment

    In this valuable study, the authors aimed to identify and characterize intrinsic factors that govern the aging process of bone marrow mesenchymal stromal cells (BMSCs), which are believed to be related to osteoporosis. The authors conclude that PCBP2 is an intrinsic aging factor, the decrease of its expression during aging results in cell proliferation activity decrease and cell senescence. The study provides convincing evidence in support of its conclusions.

Reviewed by

Read the full article See related articles

Listed in

Log in to save this article

Abstract

It has been reported that loss of PCBP2 led to increased reactive oxygen species (ROS) production and accelerated cell aging. Knockdown of PCBP2 in HCT116 cells leads to significant down-regulation of fibroblast growth factor 2 (FGF2). Here, we tried to elucidate the intrinsic factors and potential mechanisms of BMSCs aging from the interactions among PCBP2, ROS and FGF2.Unlabeled quantitative proteomics were performed to show differentially expressed proteins in the replicative senescent human-derived bone marrow stromal cells (RS-hBMSCs). ROS and FGF2 were detected in the loss-and-gain cell function experiments of PCBP2. The function recovery experiments were performed to verify whether PCBP2 regulates cell function through ROS/FGF2-dependent ways.PCBP2 expression was significantly lower in P10-hBMSCs. Knocking down the expression of PCBP2 inhibited the proliferation while accentuated the apoptosis and cell arrest of RS-hBMSCs. PCBP2 silence could increase the production of ROS. On the contrary, overexpression of PCBP2 increased the viability of both P3-hBMSCs and P10-hBMSCs significantly. Meanwhile, over-expression of PCBP2 led to significantly reduced expression of FGF2. Overexpression of FGF2 significantly offset the effect of PCBP2 overexpression in P10-hBMSCs, leading to decreased cell proliferation, increased apoptosis and reduced G0/G1 phase ratio of the cells.This study initially elucidates that PCBP2 as an intrinsic aging factor regulates the replicative senescence of hBMSCs through the ROS-FGF2 signaling axis.

Article activity feed

  1. Version published to 10.7554/elife.92419.1 on eLife
  2. Version published to 10.7554/elife.92419 on eLife
  3. eLife

    eLife assessment

    In this valuable study, the authors aimed to identify and characterize intrinsic factors that govern the aging process of bone marrow mesenchymal stromal cells (BMSCs), which are believed to be related to osteoporosis. The authors conclude that PCBP2 is an intrinsic aging factor, the decrease of its expression during aging results in cell proliferation activity decrease and cell senescence. The study provides convincing evidence in support of its conclusions.

  4. eLife

    Reviewer #1 (Public Review):

    Summary:
    This study aimed to elucidate the intrinsic factors and potential mechanisms of BMSCs aging from the interactions among PCBP2, ROS, and FGF2. This study represents the first study to reveal PCBP2 as an intrinsic aging factor to regulate the replicative senescence of hBMSCs through ROS-FGF2 signaling. This study provides convincing evidence to support the above conclusion.

    Strengths:
    This study utilized multiple in vitro approaches, such as proteomics, siRNA, and overexpression, to demonstrate that PCBP2 is an intrinsic factor of BMSC aging.

    Weaknesses:
    This study did not perform in vivo experiments.

  5. eLife

    Reviewer #2 (Public Review):

    Summary:
    The authors were trying to identify and characterize the intrinsic factors that control the process of cell aging of bone marrow mesenchymal stromal cells (BMSCs), which is believed to be related to osteoporosis.

    Strengths:
    The method is reasonable. The concept and methods used in this work can be easily extended to other systems and cells to study their aging process. It is also interesting to further examine if PCBP2 functions as an intrinsic aging factor in these other cell types.

    The results are solid, supporting the claims and conclusions. The authors successfully identified and characterized PCBP2 as one of the intrinsic aging factors for BMSC cells.

    Weaknesses:
    It is unclear if PCBP2 can also function as an intrinsic factor for BMSC cells in female individuals. More work may be needed to further dissect the mechanism of how PCBP2 impacts FGF2 expression. Could PCBP2 impact the FGF2 expression independent of ROS?

    Additional context that would help readers interpret or understand the significance of the work:
    In the current work, the authors studied the aging process of BMSC cells, which are related to osteoporosis. Aging processes also impact many other cell types and their function, such as in muscle, skin, and the brain.

  6. Version published to 10.1101/2023.10.13.23297014v1 on medRxiv