A new vaccine targeting RANKL, prepared by incorporation of an unnatural Amino acid into RANKL, prevents OVX-induced bone loss in mice
- Department of Orthopaedics, Xijing Hospital, The Fourth Military Medical University, Xi'an, 710032 (China)
- Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032 (China)
- Department of Anesthesiology and Intensive Care Unit, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou (China)
- Greehey Children's Cancer Research Institute, The University of Texas, Health Science Center, San Antonio, TX (United States)
- Department of Pharmacogenomics, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032 (China)
Highlights: • Prepared a novel vaccine targeting RANKL by incorporating a p-nitrophenylalanine into murine RANKL. • The antiserum induced by the vaccine could efficiently prevent osteoclastogenesis in vitro. • The vaccine could prevent OVX-induced bone loss in mice. Bone homeostasis is maintained by a dynamic balance between osteoblastic bone formation and osteoclastic bone resorption. The receptor activator of nuclear-κB ligand (RANKL) is essential for the function of the bone-resorbing osteoclasts, and targeting RANKL has been proved highly successful in osteoporosis patients. This study aimed to design a novel vaccine targeting RANKL and evaluate its therapeutic effects in OVX-induced bone loss model. Anti-RANKL vaccine was generated by incorporating the unnatural amino acid p-nitrophenylalanine (pNO{sub 2}Phe) into selected sites in the murine RANKL (mRANKL) molecule. Specifically, mutation of a single tyrosine residue Tyr{sup 234} (Y234) or Tyr{sup 240} (Y240) of mRANKL to pNO{sub 2}Phe (thereafter named as Y{sup 234}pNO{sub 2}Phe or Y{sup 240}pNO{sub 2}Phe) induced a high titer antibody response in mice, whereas no significant antibody response was observed for the wild type mRANKL (WT mRANKL). The antiserum induced by Y{sup 234}pNO{sub 2}Phe or Y{sup 240}pNO{sub 2}Phe could efficiently prevent osteoclastogenesis in vitro. Moreover, immunization with Y{sup 234}pNO{sub 2}Phe or Y{sup 240}pNO{sub 2}Phe could also prevent OVX-induced bone loss in mice, suggesting that selected pNO{sub 2}Phe-substituted mRANKL may pave the way for creating a novel vaccine to treat osteoporosis.
- OSTI ID:
- 23137170
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 499, Issue 3; Other Information: Copyright (c) 2018 Elsevier Inc. All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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