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<p>The current study investigated the effects of two per- and polyfluoroalkyl substances (PFASs) named perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) on osteoclastogenesis and explored the underlying mechanisms. The primary bone marrow macrophages extracted from mice were supplied for osteoclast (OC) induction, and exposed to PFOA and PFOS at the doses of 0.25, 2.5, 25, and 75&#xa0;μM during their differentiation. Real-time PCR and Western blot were used to assess the expression of OC-specific molecules and connexin 43 (Cx43). TRAP staining was performed to identify the mature OCs. Ethidium bromide uptake experiments were adopted to evaluate the hemichannel activity. For mechanism exploration, the hemichannel inhibitor, carbenoxolone (CBX), was used to incubate the cells during PFAS exposure. According to the results of our experiments, the PFASs promoted osteoclastogenesis and enhanced the Cx43 expression and hemichannel activity. After the treatment of CBX, the promoted osteoclastogenesis was significantly down-regulated, indicating the critical role of hemichannels.</p>

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Perfluorooctanoic acid and perfluorooctane sulfonate promote osteoclastogenesis in vitro through the activation of hemichannels

  • 期刊论文

  • 发表日期：

    2025年12月12日

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  • Sijia Yang,
  • Mengyuan Chen,
  • Di Yang,
  • Furong Deng,
  • Xinbiao Guo

摘要

The current study investigated the effects of two per- and polyfluoroalkyl substances (PFASs) named perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) on osteoclastogenesis and explored the underlying mechanisms. The primary bone marrow macrophages extracted from mice were supplied for osteoclast (OC) induction, and exposed to PFOA and PFOS at the doses of 0.25, 2.5, 25, and 75 μM during their differentiation. Real-time PCR and Western blot were used to assess the expression of OC-specific molecules and connexin 43 (Cx43). TRAP staining was performed to identify the mature OCs. Ethidium bromide uptake experiments were adopted to evaluate the hemichannel activity. For mechanism exploration, the hemichannel inhibitor, carbenoxolone (CBX), was used to incubate the cells during PFAS exposure. According to the results of our experiments, the PFASs promoted osteoclastogenesis and enhanced the Cx43 expression and hemichannel activity. After the treatment of CBX, the promoted osteoclastogenesis was significantly down-regulated, indicating the critical role of hemichannels.