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Alpha-lipoic acid inhibits TNF-alpha-induced apoptosis in human bone marrow stromal cells

Chang-Hyun Byun1, Jung-Min Koh, Dong Kwan Kim

  • 1Asan Institute for Life Sciences, Seoul, Republic of Korea.

Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research
|June 9, 2005
PubMed
Abstract

Insights

Tumor Necrosis Factor-alpha (TNF-alpha) increases oxidative stress and apoptosis in bone cells. Alpha-lipoic acid (alpha-LA) demonstrated protective effects, suggesting its potential for treating bone loss.

Area of Science:

  • Cell Biology
  • Bone Biology
  • Oxidative Stress Research

Background:

  • Oxidative stress is a key factor in bone loss, particularly post-menopause.
  • Tumor Necrosis Factor-alpha (TNF-alpha) exacerbates oxidative stress and is implicated in menopausal bone loss.
  • Human bone marrow stromal cells (hBMSCs) are susceptible to TNF-alpha and hydrogen peroxide (H2O2)-induced apoptosis.

Purpose of the Study:

  • To investigate the role of reactive oxygen species (ROS) in TNF-alpha-induced apoptosis of hBMSCs.
  • To analyze the protective effects of alpha-lipoic acid (alpha-LA) against TNF-alpha and H2O2-induced apoptosis.
  • To elucidate the signaling pathways (caspases, JNK, NF-kappaB) involved in TNF-alpha-mediated bone cell apoptosis.

Main Methods:

  • Utilized the HS-5 hBMSC cell line for experiments.
  • Assessed apoptosis using MTT assay, trypan blue exclusion, and DNA fragmentation analysis.
  • Determined ROS levels, glutathione levels, and activation of caspases, JNK, and NF-kappaB via Western blotting and enzyme immunoassay.

Main Results:

  • TNF-alpha and H2O2 significantly increased intracellular ROS and decreased glutathione levels in hBMSCs.
  • Both agents induced apoptosis by activating caspases-3, -9, and -8.
  • Apoptosis was mediated through the activation of c-jun N-terminal kinase (JNK) and NF-kappaB pathways.
  • Pretreatment with alpha-Lipoic acid (alpha-LA) effectively prevented TNF-alpha and H2O2-induced oxidative stress and apoptosis.

Conclusions:

  • TNF-alpha induces oxidative stress and apoptosis in hBMSCs via ROS generation and activation of JNK and NF-kappaB.
  • Alpha-lipoic acid (alpha-LA) shows promise as a therapeutic agent to mitigate bone loss associated with oxidative stress.
  • These findings highlight the therapeutic potential of alpha-LA in conditions characterized by increased oxidative stress and bone resorption.

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