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Study · In vitro (cells) · 2021

5 results

Senolytic Peptide FOXO4-DRI Selectively Removes Senescent Cells From in vitro Expanded Human Chondrocytes.

Huang Y, He Y, Makarcyzk MJ, Lin H

Frontiers in bioengineering and biotechnology29 Apr 2021Cited by 42 (Europe PMC)

PMID33996787 (opens in a new tab)PMCIDPMC8116695 (opens in a new tab)DOI10.3389/fbioe.2021.677576 (opens in a new tab)PepBankPUB-33996787
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Summary

Autologous chondrocyte implantation (ACI) is a procedure used to treat articular cartilage injuries and prevent the onset of post-traumatic osteoarthritis. In vitro expansion of chondrocytes, a necessary step in ACI, results in the generation of senescent cells that adversely affect the quality and quantity of newly formed cartilage. Recently, a senolytic peptide, fork head box O transcription factor 4-D-Retro-Inverso (FOXO4-DRI), was reported to selectively kill the senescent fibroblasts. In this study, we hypothesized that FOXO4-DRI treatment could remove the senescent cells in the expanded chondrocytes, thus enhancing their potential in generating high-quality cartilage. To simulate the in vitro expansion for ACI, chondrocytes isolated from healthy donors were expanded to population doubling level (PDL) 9, representing chondrocytes ready for implantation. Cells at PDL3 were also used to serve as the minimally expanded control. Results showed that the treatment of FOXO4-DRI removed more than half of the cells in PDL9 but did not significantly affect the cell number of PDL3 chondrocytes. Compared to the untreated control, the senescence level in FOXO4-DRI treated PDL9 chondrocytes was significantly reduced. Based on the result from standard pellet culture, FOXO4-DRI pre-treatment did not enhance the chondrogenic potential of PDL9 chondrocytes. However, the cartilage tissue generated from FOXO4-DRI pretreated PDL9 cells displayed lower expression of senescence-relevant secretory factors than that from the untreated control group. Taken together, FOXO4-DRI is able to remove the senescent cells in PDL9 chondrocytes, but its utility in promoting cartilage formation from the in vitro expanded chondrocytes needs further investigation.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study5

5 results from studies that gave the peptide. No result from this study comes from people.

  1. 01LabIn vitro (cells)Efficacy outcome

    In expanded human chondrocytes at PDL9, FOXO4‑DRI removed more than half of the cells.

    In plain wordsIn lab tests, FOXO4‑DRI removed more than half of the aged, expanded cartilage cells.

    Peptide
    FOXO4-DRI
    Outcome
    DecreaseCell number of PDL9 chondrocytes
    Study

    humann: not reported in source

    In vitro expanded human chondrocytes (PDL9 and PDL3)
    Outcome group
    Cell viability and death · Musculoskeletal
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Results showed that the treatment of FOXO4-DRI removed more than half of the cells in PDL9 but did not significantly affect the cell number of PDL3 chondrocytes.
    1 context sentence
    Summary · context
    To simulate the in vitro expansion for ACI, chondrocytes isolated from healthy donors were expanded to population doubling level (PDL) 9, representing chondrocytes ready for implantation.
  2. 02LabIn vitro (cells)Efficacy outcome

    In minimally expanded human chondrocytes at PDL3, FOXO4‑DRI did not significantly affect the cell number.

    In plain wordsIn lab tests, FOXO4‑DRI did not change the number of lightly expanded cartilage cells.

    Peptide
    FOXO4-DRI
    Outcome
    No significant changeCell number of PDL3 chondrocytes
    Study

    humann: not reported in source

    In vitro expanded human chondrocytes (PDL9 and PDL3)
    Outcome group
    Cell viability and death · Musculoskeletal
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Results showed that the treatment of FOXO4-DRI removed more than half of the cells in PDL9 but did not significantly affect the cell number of PDL3 chondrocytes.
    1 context sentence
    Summary · context
    To simulate the in vitro expansion for ACI, chondrocytes isolated from healthy donors were expanded to population doubling level (PDL) 9, representing chondrocytes ready for implantation.
  3. 03LabIn vitro (cells)Efficacy outcome

    In PDL9 chondrocytes, senescence level was significantly lower with FOXO4‑DRI than in the untreated control.

    In plain wordsIn lab tests, aged cartilage cells showed less senescence with FOXO4‑DRI than without it.

    Peptide
    FOXO4-DRI
    Outcome
    DecreaseSenescence level in PDL9 chondrocytes
    Study

    humann: not reported in source

    In vitro expanded human chondrocytes (PDL9 and PDL3)
    Comparator
    Untreated control
    Outcome group
    Aging markers · Musculoskeletal
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Compared to the untreated control, the senescence level in FOXO4-DRI treated PDL9 chondrocytes was significantly reduced.
    1 context sentence
    Summary · context
    To simulate the in vitro expansion for ACI, chondrocytes isolated from healthy donors were expanded to population doubling level (PDL) 9, representing chondrocytes ready for implantation.
  4. 04LabIn vitro (cells)Efficacy outcome

    In standard pellet culture, FOXO4‑DRI pre-treatment did not enhance the chondrogenic potential of PDL9 chondrocytes.

    In plain wordsIn lab tests, FOXO4‑DRI pre-treatment did not improve the ability of aged cartilage cells to form cartilage.

    Peptide
    FOXO4-DRI
    Outcome
    No significant changeChondrogenic potential of PDL9 chondrocytes
    Study

    humann: not reported in source

    In vitro expanded human chondrocytes (PDL9 and PDL3)
    Outcome group
    Bone and joint · Musculoskeletal
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Based on the result from standard pellet culture, FOXO4-DRI pre-treatment did not enhance the chondrogenic potential of PDL9 chondrocytes.
    1 context sentence
    Summary · context
    To simulate the in vitro expansion for ACI, chondrocytes isolated from healthy donors were expanded to population doubling level (PDL) 9, representing chondrocytes ready for implantation.
  5. 05LabIn vitro (cells)Efficacy outcome

    Cartilage tissue generated from FOXO4‑DRI pretreated PDL9 cells showed lower expression of senescence-relevant secretory factors than the untreated control group.

    In plain wordsIn lab tests, cartilage grown from FOXO4‑DRI pretreated cells had lower levels of aging-related signals than cartilage from untreated cells.

    Peptide
    FOXO4-DRI
    Outcome
    DecreaseSenescence-relevant secretory factors in generated cartilage
    Study

    humann: not reported in source

    In vitro expanded human chondrocytes (PDL9 and PDL3)
    Comparator
    Untreated control
    Outcome group
    Aging markers · Musculoskeletal
    Studied dose
    Dose not stated

    Source sentences

    Summary
    However, the cartilage tissue generated from FOXO4-DRI pretreated PDL9 cells displayed lower expression of senescence-relevant secretory factors than that from the untreated control group.
    1 context sentence
    Summary · context
    To simulate the in vitro expansion for ACI, chondrocytes isolated from healthy donors were expanded to population doubling level (PDL) 9, representing chondrocytes ready for implantation.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    13 Oct 2026, 21:44 UTC

    Study results updated

  2. Version 1

    13 Oct 2026, 16:31 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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