2. Academic Validation
  3. Kaempferol attenuates wear particle-induced inflammatory osteolysis via JNK and p38-MAPK signaling pathways

Kaempferol attenuates wear particle-induced inflammatory osteolysis via JNK and p38-MAPK signaling pathways

  • J Ethnopharmacol. 2023 Aug 11;318(Pt B):117019. doi: 10.1016/j.jep.2023.117019.
Xin Yu 1,  Qi Wu 2,  Zhengrong Ren 3,  Bin Chen 1,  Dongsheng Wang 1,  Tao Yuan 1,  Hao Ding 1,  Yang Wang 1,  Guodong Yuan 1,  Yuxiang Wang 1,  Lei Zhang 4,  Jianning Zhao 5,  Zhongyang Sun 6
Affiliations

Affiliations

  • 1 Department of Orthopedics, Affiliated Jinling Hospital, Medical School, Nanjing University, Nanjing, 210093, China.
  • 2 Department of Orthopedics, Affiliated Jinling Hospital, Medical School, Nanjing University, Nanjing, 210093, China; Department of Vascular Surgery, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, 102218, China.
  • 3 State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing, 210023, China.
  • 4 Department of Orthopedics, Affiliated Jinling Hospital, Medical School, Nanjing University, Nanjing, 210093, China. Electronic address: [email protected].
  • 5 Department of Orthopedics, Affiliated Jinling Hospital, Medical School, Nanjing University, Nanjing, 210093, China. Electronic address: [email protected].
  • 6 Department of Orthopedics, Affiliated Jinling Hospital, Medical School, Nanjing University, Nanjing, 210093, China; Department of Orthopedics, Air Force Hospital of Eastern Theater, Anhui Medical University, Nanjing, 210002, China. Electronic address: [email protected].
PMID: 37574017 DOI: 10.1016/j.jep.2023.117019
Abstract

Ethnopharmacological relevance: Wear particle-induced inflammatory osteoclast activation is a master contributor to periprosthetic osteolysis, which can cause pathological bone loss and destruction. Hence, inhibiting inflammation and osteoclastogenesis is an important strategy for preventing wear particle-induced osteolysis. To date, there are no FDA-approved non-surgical pharmacotherapies for arresting periprosthetic osteolysis. Kaempferol (KAE), a natural flavonol abundant in many traditional Chinese herbal medicines, has been shown to have protective effects against inflammatory bone diseases such as rheumatoid arthritis, but no previous study has evaluated the effects of KAE on wear particle-induced osteolysis.

Aim of the study: The study aimed to investigate the effects of KAE on wear particle-induced inflammatory osteolysis and osteoclast activation, and further explore the underlying mechanisms.

Materials and methods: TiAl6V4 metal particles (TiPs) were retrieved from the prosthesis of patients who underwent revision hip arthroplasty due to aseptic loosening. A mouse calvarial osteolysis model was used to investigate the effects of KAE on wear particle-induced inflammatory osteolysis in vivo. Primary bone marrow-derived macrophages (BMMs) were used to explore the effects of KAE on osteoclast differentiation and bone-resorbing activity as well as the underlying mechanisms in vitro.

Results: In the present study, we found that KAE alleviated wear particle-induced inflammatory bone loss in vivo and inhibited osteoclast differentiation and function in vitro. Furthermore, we revealed that KAE exerted anti-osteoclastogenic effects by downregulating JNK and p38-MAPK signaling as well as the downstream NFATc1 expression.

Conclusions: KAE is an alternative therapeutic agent for preventing and treating periprosthetic osteolysis and aseptic loosening.

Keywords

Inflammation; JNK; Kaempferol; Osteoclastogenesis; Periprosthetic osteolysis; p38-MAPK.

Figures
Products