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
  • 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: [email protected].
  • 7. Department of Orthopedic, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China. Electronic address: [email protected].
  • 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: [email protected].
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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