Biomaterials Translational ›› 2021, Vol. 2 ›› Issue (2): 143-150.doi: 10.12336/biomatertransl.2021.02.004

• RESEARCH ARTICLE • Previous Articles     Next Articles

Role of hypoxia inducible factor 1α in cobalt nanoparticle induced cytotoxicity of human THP-1 macrophages

Wendy Rachel Francis1,#, Zhao Liu1,2,#, Sian E Owens1, Xiao Wang1,3, Huaming Xue4, Alex Lord1, Venkateswarlu Kanamarlapudi1, Zhidao Xia1,*()   

  1. 1 Centre for Nanohealth, Swansea University Medical School, Swansea, UK
    2 Department of Orthopaedic Surgery, Orthopaedic Institute, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China
    3 Department of Orthopaedic Surgery, Johns Hopkins School of Medicine, Baltimore, MD, USA
    4 Department of Orthopaedics, Yangpu Hospital affiliated to Tongji University School of Medicine, Shanghai, China.
  • Received:2021-01-26 Revised:2021-06-07 Accepted:2021-06-09 Online:2021-06-28 Published:2021-06-28
  • Contact: Zhidao Xia E-mail:z.xia@swansea.ac.uk
  • About author:#Author Equally.


Cobalt is one of the main components of metal hip prostheses and cobalt nanoparticles (CoNPs) produced from wear cause inflammation, bone lyses and cytotoxicity at high concentrations. Cobalt ions mimic hypoxia in the presence of normal oxygen levels, and activate hypoxic signalling by stabilising hypoxia inducible transcription factor 1α (HIF1α). This study aimed to assess in vitro the functional role of HIF1α in CoNP induced cellular cytotoxicity. HIF1α, lysosomal pH, tumour necrosis factor α and interleukin 1β expression were analysed in THP-1 macrophages treated with CoNP (0, 10 and 100 μg/mL). HIF1α knock out assays were performed using small interfering RNA to assess the role of HIF1α in CoNP-induced cytotoxicity. Increasing CoNP concentration increased lysosomal activity and acidity in THP-1 macrophages. Higher doses of CoNP significantly reduced cell viability, stimulated caspase 3 activity and apoptosis. Reducing HIF1α activity increased the pro-inflammatory activity of tumour necrosis factor α and interleukin 1β, but had no significant impact on cellular cytotoxicity. This suggests that whilst CoNP promotes cytotoxicity and cellular inflammation, the apoptotic mechanism is not dependent on HIF1α.

Key words: cobalt nanoparticle, cytotoxicity, hypoxia inducible factor, macrophages, TNFα