title: Kinesin superfamily protein 17 contributes to the development of bone cancer pain by participating in NR2B transport in the spinal cord of mice.
abstract: Τreatment of bone cancer pain remains a challenge, while the mechanisms causing the pain remain elusive. We demonstrated that the expression of the N‑methyl‑D‑aspartate (NMDA) receptor NR2B subunit was upregulated in mice with bone cancer pain. Kinesin superfamily protein 17 (KIF17), a recently characterized member of the kinesin superfamily proteins, has been demonstrated to transport and deliver the NR2B subunit to dendrites in mammalian neurons. In the present study, we induced bone cancer pain via femur bone cavity osteosarcoma NCTC 2472 tumor cell implantation (TCI) in mice. The results showed that TCI in mice increased the number of spontaneous flinches, mechanical allodynia events, expression of spinal KIF17 and NR2B subunits. Intrathecal administration of KIF17 antisense oligodeoxynucleotide (ODN) attenuated the behavioral signs of bone cancer pain and suppressed the increased expression of NR2B induced by TCI. In addition, KIF17 binds to a protein complex that contains mLin‑10 to transport NR2B, and we determined that the increase of mLin‑10 was suppressed following admini-stration. Thus, these findings suggested that KIF17 contributed to the development of bone cancer pain in the spinal cord through NR2B transport and that mLin‑10 may also play a role in pain development.
authors.affiliation: Department of Anesthesiology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, P.R. China.
authors.forename: Ming
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, P.R. China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, P.R. China.
authors.forename: Bailing
authors.initials: B
authors.lastname: Hou
authors.affiliation: Department of Anesthesiology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, P.R. China.
authors.forename: Dan
authors.initials: D
authors.lastname: Bu
authors.affiliation: Department of Anesthesiology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, P.R. China.
authors.forename: Linyu
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of Anesthesiology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, P.R. China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Gu
authors.affiliation: Department of Anesthesiology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, P.R. China.
authors.forename: Zhengliang
authors.initials: Z
authors.lastname: Ma
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D001859:Bone Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D055786:Gene Knockout Techniques; D016547:Kinesins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides / Q000235:genetics; D012516:Osteosarcoma / Q000473:pathology; D010146:Pain / Q000473:pathology*; D011485:Protein Binding; D021381:Protein Transport; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C513072:Apba1 protein, mouse; C409642:KIF17 protein, mouse; D008565:Membrane Proteins; C121001:NR2B NMDA receptor; D009419:Nerve Tissue Proteins; D009838:Oligodeoxyribonucleotides; D016194:Receptors, N-Methyl-D-Aspartate; D016547:Kinesins