1. Academic Validation
  2. IL-17 promotes osteoclast-induced bone loss by regulating glutamine-dependent energy metabolism

IL-17 promotes osteoclast-induced bone loss by regulating glutamine-dependent energy metabolism

  • Cell Death Dis. 2024 Feb 5;15(2):111. doi: 10.1038/s41419-024-06475-2.
Renpeng Peng # 1 Yimin Dong # 1 Meng Zheng 1 Honglei Kang 1 Pengju Wang 1 Meipeng Zhu 1 Kehan Song 2 Wei Wu 3 Feng Li 4
Affiliations

Affiliations

  • 1 Department of Orthopedic Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
  • 2 Department of Orthopedic Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China. kehansong@tjh.tjmu.edu.cn.
  • 3 Department of Orthopedic Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China. wuweisheit@hotmail.com.
  • 4 Department of Orthopedic Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China. lifengmd@hust.edu.cn.
  • # Contributed equally.
Abstract

Osteoclasts consume an amount of adenosine triphosphate (ATP) to perform their bone resorption function in the development of osteoporosis. However, the mechanism underlying osteoclast energy metabolism has not been fully elucidated. In addition to glucose, glutamine (Glu) is another major energy carrier to produce ATP. However, the role of Glu metabolism in osteoclasts and the related molecular mechanisms has been poorly elucidated. Here we show that Glu is required for osteoclast differentiation and function, and that Glu deprivation or pharmacological inhibition of Glu transporter ASCT2 by V9302 suppresses osteoclast differentiation and their bone resorptive function. In vivo treatment with V9302 improved OVX-induced bone loss. Mechanistically, RNA-seq combined with in vitro and in vivo experiments suggested that Glu mediates the role of IL-17 in promoting osteoclast differentiation and in regulating energy metabolism. In vivo IL-17 treatment exacerbated OVX-induced bone loss, and this effect requires the participation of Glu or its downstream metabolite α-KG. Taken together, this study revealed a previously unappreciated regulation of IL-17 on energy metabolism, and this regulation is Glu-dependent. Targeting the IL-17-Glu-energy metabolism axis may be a potential therapeutic strategy for the treatment of osteoporosis and other IL-17 related diseases.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-112683
    99.88%, ASCT2 Antagonist