Gö6983 attenuates titanium particle-induced osteolysis and RANKL mediated osteoclastogenesis through the suppression of NFκB/JNK/p38 pathways

  • Biochem Biophys Res Commun. 2018 Sep 3;503(1):62-70. doi: 10.1016/j.bbrc.2018.05.177.
Wenyu Feng  1 Jia Li  2 Shijie Liao  1 Shiting Ma  1 Feicui Li  3 Chaoyi Zhong  4 Guodong Li  4 Yan Wei  2 Huading Huang  5 Qingjun Wei  6 Jun Yao  7 Yun Liu  8
Affiliations
  • 1. Departments of Orthopedics, The First Affliated Hospital of Guangxi Medical University, Nanning, Guangxi, China; Research Centre for Regenerative Medicine, Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Nanning, Guangxi, China.
  • 2. Departments of Pathology, The First Affliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
  • 3. Departments of General Medicine, The First Affliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
  • 4. Research Centre for Regenerative Medicine, Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Nanning, Guangxi, China.
  • 5. Departments of Cardiothoracic Surgery, The First Affliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
  • 6. Departments of Orthopedics, The First Affliated Hospital of Guangxi Medical University, Nanning, Guangxi, China; Research Centre for Regenerative Medicine, Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Nanning, Guangxi, China. Electronic address: [email protected].
  • 7. Departments of Orthopedics, The First Affliated Hospital of Guangxi Medical University, Nanning, Guangxi, China; Research Centre for Regenerative Medicine, Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Nanning, Guangxi, China. Electronic address: [email protected].
  • 8. Departments of Orthopedics, The First Affliated Hospital of Guangxi Medical University, Nanning, Guangxi, China; Research Centre for Regenerative Medicine, Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Nanning, Guangxi, China. Electronic address: [email protected].
Abstract

Osteoclast activation by wear particles has caused major difficulties for surgeons. Wear particles are the main causes of aseptic prosthetic loosening. Gö6983, a protein kinase C inhibitor, inhibits five subtypes of protein kinase C family members. Here, we found that Gö6983 had an obviously inhibitory effect on wear-particles-induced osteolysis in vivo. In vitro, Gö6983 inhibited RANKL-stimulated osteoclast formation and function by inhibiting the RANKL-stimulated nuclear factor-κB/JNK/p38 signaling pathway. We also observed that Go6983 had no effect on the differentiation of osteoblasts and osteoblast-associated genes expression. According to our data, Gö6983 has potential therapeutic effects for aseptic prosthetic loosening caused by osteoclast activation.

Keywords
Gö6983; Osteoclast; RANKL; Titanium particle.
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