2. Academic Validation
  3. Oleandrin inhibits osteoclast differentiation by targeting the LRP4/MAPK/NF-κB signalling pathway to treat osteoporosis

Oleandrin inhibits osteoclast differentiation by targeting the LRP4/MAPK/NF-κB signalling pathway to treat osteoporosis

  • Int Immunopharmacol. 2025 Feb 20:148:114073. doi: 10.1016/j.intimp.2025.114073.
Chongxin Xiang 1,  Jiankang Cao 2,  Rui Hu 1,  Kaixuan Li 3,  Tingyu Meng 4,  Yutao Xia 5,  Qunbo Meng 1,  Kaiwen Liu 6,  Lian Liu 7,  Xuetao Zhu 8
Affiliations

Affiliations

  • 1 Department of Orthopedic, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China.
  • 2 Department of Pain, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China.
  • 3 Department of Neurosurgery, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui 233004, China.
  • 4 Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan 250012, China.
  • 5 Department of Oncology, YiDu Central Hospital of Weifang, Weifang, Shandong 262500, China.
  • 6 Department of Orthopedic, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China. Electronic address: 904893724@qq.com.
  • 7 Department of Orthopedic, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China. Electronic address: 17865153925@163.com.
  • 8 Department of Orthopedic, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China; Department of Emergency and Critical Care Medicine, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School of Nanjing Medical University, China. Electronic address: 531359970@qq.com.
PMID: 39823799 DOI: 10.1016/j.intimp.2025.114073
Abstract

Osteoporosis is a common inflammation-related disease in which the release of proinflammatory cytokines promotes bone loss. Oleandrin is a monomer compound extracted from the leaves of the Nerium oleander plant, has been shown to exert an anti-inflammatory effect on a variety of inflammation-related diseases. However, its role in osteoporosis and the underlying mechanisms remain unclear. In this study, Oleandrin was shown to reduce bone loss in ovariectomy-induced osteoporotic mice in vivo. Additionally, Oleandrin inhibited RANKL-induced osteoclast differentiation in a concentration-dependent manner in vitro. Signalling pathway studies showed that Oleandrin could inhibit osteoclast differentiation by targeting MAPK and NF-κB signalling pathways. Further mechanistic studies showed that Oleandrin binds to low-density lipoprotein receptor-related protein 4 in osteoclast, thereby exerting inhibitory effects on osteoclast differentiation. In conclusion, this study lays the foundation for further research on the anti-inflammatory and anti-osteoporotic effects of Oleandrin on osteoporosis and its underlying mechanism and provides new possibilities for the treatment of osteoporosis.

Keywords

LRP4; MAPK/NF-κB; Oleandrin; Osteoclast; Osteoporosis.

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