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Study · Animal study (in vivo) · mouse · 2024

5 results

Humanin Treatment Protects Against Venetoclax-Induced Bone Growth Retardation in Ex Vivo Cultured Rat Bones.

Velentza L, Wickström M, Kogner P, Ohlsson C, Zaman F, Sävendahl L

Journal of the Endocrine Society25 Jan 2024Cited by 3 (Europe PMC)

Summary

ContextRecent preclinical studies reported that the BCL-2 inhibitor venetoclax can impair bone growth. A strategy to prevent such a side effect of this promising anticancer drug is highly desired. Earlier in vitro and in vivo studies suggested that the mitochondrial peptide humanin has the potential to prevent drug-induced growth impairment.ObjectiveWe hypothesized that co-treatment with the humanin analog HNG may prevent venetoclax-induced bone growth impairment.MethodsEx vivo studies were performed in fetal rat metatarsal bones and human growth plate samples cultured for 12 and 2 days, respectively, while in vivo studies were performed in young neuroblastoma mice being treated daily for 14 days. The treatment groups included venetoclax, HNG, venetoclax plus HNG, or vehicle. Bone growth was continuously monitored and at the end point, histomorphometric and immunohistochemical analyses were performed in fixed tissues.ResultsVenetoclax suppressed metatarsal bone growth and when combined with HNG, bone growth was rescued and all histological parameters affected by venetoclax monotherapy were normalized. Mechanistic studies showed that HNG downregulated the pro-apoptotic proteins Bax and p53 in cultured metatarsals and human growth plate tissues, respectively. The study in a neuroblastoma mouse model confirmed a growth-suppressive effect of venetoclax treatment. In this short-term in vivo study, no significant bone growth-rescuing effect could be verified when testing HNG at a single dose. We conclude that humanin dose-dependently protects ex vivo cultured metatarsal bones from venetoclax-induced bone growth impairment by restoring the growth plate microstructure.
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. 01AnimalAnimal study (in vivo)Efficacy outcome

    In neuroblastoma mice given venetoclax, a single dose of HNG did not significantly rescue bone growth in this short-term study.

    In plain wordsIn mice, a single dose of a humanin analog did not significantly rescue bone growth affected by venetoclax in this short study.

    Peptide
    Humanin
    Outcome
    No significant changeBone growth rescue in vivo
    Study

    mousen: not reported in source

    Young neuroblastoma mice treated with venetoclax
    Comparator
    Venetoclax alone
    Outcome group
    Bone and joint · Musculoskeletal
    Studied dose
    single dose · 14 daysAs given in this study (mouse).

    Source sentences

    Summary
    In this short-term in vivo study, no significant bone growth-rescuing effect could be verified when testing HNG at a single dose.
    2 context sentences
    Summary · context
    Ex vivo studies were performed in fetal rat metatarsal bones and human growth plate samples cultured for 12 and 2 days, respectively, while in vivo studies were performed in young neuroblastoma mice being treated daily for 14 days.
    Summary · context
    The treatment groups included venetoclax, HNG, venetoclax plus HNG, or vehicle.
  2. 02LabEx vivo tissueEfficacy outcome

    In cultured fetal rat metatarsal bones, adding HNG to venetoclax rescued the bone growth that venetoclax suppressed.

    In plain wordsIn lab-cultured rat bones, a humanin analog restored bone growth that the cancer drug venetoclax had suppressed.

    Peptide
    Humanin
    Outcome
    IncreaseMetatarsal bone growth with venetoclax
    Study

    ratn: not reported in source

    Fetal rat metatarsal bones
    Comparator
    Venetoclax alone
    Outcome group
    Bone and joint · Musculoskeletal
    Studied dose
    Dose not stated · 12 daysAs given in this study (rat).

    Source sentences

    Summary
    Venetoclax suppressed metatarsal bone growth and when combined with HNG, bone growth was rescued and all histological parameters affected by venetoclax monotherapy were normalized.
    2 context sentences
    Summary · context
    Ex vivo studies were performed in fetal rat metatarsal bones and human growth plate samples cultured for 12 and 2 days, respectively, while in vivo studies were performed in young neuroblastoma mice being treated daily for 14 days.
    Summary · context
    The treatment groups included venetoclax, HNG, venetoclax plus HNG, or vehicle.
  3. 03LabEx vivo tissueEfficacy outcome

    In cultured fetal rat metatarsal bones, adding HNG to venetoclax normalized all histological parameters that venetoclax monotherapy had affected.

    In plain wordsIn lab-cultured rat bones, a humanin analog brought bone tissue structure back to normal despite venetoclax.

    Peptide
    Humanin
    Outcome
    MixedHistological parameters affected by venetoclax
    Study

    ratn: not reported in source

    Fetal rat metatarsal bones
    Comparator
    Venetoclax alone
    Outcome group
    Bone and joint · Musculoskeletal
    Studied dose
    Dose not stated · 12 daysAs given in this study (rat).

    Source sentences

    Summary
    Venetoclax suppressed metatarsal bone growth and when combined with HNG, bone growth was rescued and all histological parameters affected by venetoclax monotherapy were normalized.
    2 context sentences
    Summary · context
    Ex vivo studies were performed in fetal rat metatarsal bones and human growth plate samples cultured for 12 and 2 days, respectively, while in vivo studies were performed in young neuroblastoma mice being treated daily for 14 days.
    Summary · context
    The treatment groups included venetoclax, HNG, venetoclax plus HNG, or vehicle.
  4. 04LabEx vivo tissueMechanism

    In cultured fetal rat metatarsals, HNG downregulated the pro-apoptotic protein Bax.

    In plain wordsIn lab-cultured rat bones, a humanin analog lowered a protein that promotes cell death.

    Peptide
    Humanin
    Outcome
    DecreaseBax protein in metatarsals
    Study

    ratn: not reported in source

    Cultured fetal rat metatarsal bones
    Outcome group
    Cell viability and death · Musculoskeletal
    Studied dose
    Dose not stated · 12 daysAs given in this study (rat).

    Source sentences

    Summary
    Mechanistic studies showed that HNG downregulated the pro-apoptotic proteins Bax and p53 in cultured metatarsals and human growth plate tissues, respectively.
    1 context sentence
    Summary · context
    Ex vivo studies were performed in fetal rat metatarsal bones and human growth plate samples cultured for 12 and 2 days, respectively, while in vivo studies were performed in young neuroblastoma mice being treated daily for 14 days.
  5. 05LabEx vivo tissueMechanism

    In cultured human growth plate tissue, HNG downregulated the pro-apoptotic protein p53.

    In plain wordsIn lab-cultured human growth plate tissue, a humanin analog lowered a protein that promotes cell death.

    Peptide
    Humanin
    Outcome
    Decreasep53 protein in human growth plate tissue
    Study

    humann: not reported in source

    Cultured human growth plate samples
    Outcome group
    Cell viability and death · Musculoskeletal
    Studied dose
    Dose not stated · 2 daysAs given in this study (human).

    Source sentences

    Summary
    Mechanistic studies showed that HNG downregulated the pro-apoptotic proteins Bax and p53 in cultured metatarsals and human growth plate tissues, respectively.
    1 context sentence
    Summary · context
    Ex vivo studies were performed in fetal rat metatarsal bones and human growth plate samples cultured for 12 and 2 days, respectively, while in vivo studies were performed in young neuroblastoma mice being treated daily for 14 days.

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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