1. Academic Validation
  2. Scutellarin inhibits RANKL-mediated osteoclastogenesis and titanium particle-induced osteolysis via suppression of NF-κB and MAPK signaling pathway

Scutellarin inhibits RANKL-mediated osteoclastogenesis and titanium particle-induced osteolysis via suppression of NF-κB and MAPK signaling pathway

  • Int Immunopharmacol. 2016 Nov;40:458-465. doi: 10.1016/j.intimp.2016.09.031.
Shuai Zhao 1 Yu Sun 2 Xiaolei Li 3 Jingcheng Wang 4 Lianqi Yan 5 Zhen Zhang 2 Daxin Wang 6 Jihang Dai 2 Jun He 2 Shuguang Wang 2
Affiliations

Affiliations

  • 1 Department of Orthopedics, Xiangya Second Hospital, Central South University, Changsha, Hunan 410012, China. Electronic address: zhaoshuai19870624@163.com.
  • 2 Department of Orthopedics, Clinical medical college of Yangzhou University, Nantong West Road 98, Yangzhou, Jiangsu 225001, China; Orthopedics Institute, Subei People's Hospital of Jiangsu Province, Yangzhou, Jiangsu 225001, China.
  • 3 Department of Orthopedics, Xiangya Second Hospital, Central South University, Changsha, Hunan 410012, China; Department of Orthopedics, Clinical medical college of Yangzhou University, Nantong West Road 98, Yangzhou, Jiangsu 225001, China; Orthopedics Institute, Subei People's Hospital of Jiangsu Province, Yangzhou, Jiangsu 225001, China.
  • 4 Department of Orthopedics, Xiangya Second Hospital, Central South University, Changsha, Hunan 410012, China; Department of Orthopedics, Clinical medical college of Yangzhou University, Nantong West Road 98, Yangzhou, Jiangsu 225001, China; Orthopedics Institute, Subei People's Hospital of Jiangsu Province, Yangzhou, Jiangsu 225001, China. Electronic address: jingchengwyz@163.com.
  • 5 Department of Orthopedics, Xiangya Second Hospital, Central South University, Changsha, Hunan 410012, China; Department of Orthopedics, Clinical medical college of Yangzhou University, Nantong West Road 98, Yangzhou, Jiangsu 225001, China; Orthopedics Institute, Subei People's Hospital of Jiangsu Province, Yangzhou, Jiangsu 225001, China. Electronic address: yanlianqi@126.com.
  • 6 Department of Orthopedics, Xiangya Second Hospital, Central South University, Changsha, Hunan 410012, China; Department of Orthopedics, Clinical medical college of Yangzhou University, Nantong West Road 98, Yangzhou, Jiangsu 225001, China.
Abstract

Aseptic prosthetic loosening is a major complication after hip joint replacement. Wear particle-induced periprosthetic osteolysis plays a key role in aseptic prosthetic loosening. Attempting to modulate receptor activator of nuclear factor-κB (RANKL) mediated signaling pathways is a promising strategy to prevent aseptic prosthetic loosening. In the present study, we determined the effect of scutellarin (SCU) on titanium (Ti) particle-induced osteolysis in a mouse calvarial model and RANKL-mediated osteoclastogenesis. We determined that SCU, the major effective constituent of breviscapine isolated from a Chinese herb, has potential effects on preventing Ti particle-caused osteolysis in calvarial model of mouse. In vitro, SCU could suppress RANKL-mediated osteoclastogenesis, the function of osteoclast bone resorption, and the expression levels of osteoclast-specific genes (tartrate-resistant Acid Phosphatase (TRAP), Cathepsin K, c-Fos, NFATc1). Further investigation indicated that SCU could inhibit RANKL-mediated MAPK and NF-κB signaling pathway, including JNK1/2, p38, ERK1/2, and IκBα phosphorylation. Taken together, these results indicate that SCU could inhibit osteoclastogenesis and prevent Ti particle-induced osteolysis by suppressing RANKL-mediated MAPK and NF-κB signaling pathway. These results suggest that SCU is a promising therapeutic agent for preventing wear particle-induced periprosthetic osteolysis.

Keywords

Aseptic loosening; MAPKs; NF-κB; Osteoclast; Osteolysis; Scutellarin.

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