title: Secreted phosphoprotein 24 kD inhibits nerve root inflammation induced by bone morphogenetic protein-2.
abstract: BACKGROUND
  Bone morphogenetic protein-2 (BMP-2) has been used to successfully promote spine fusion, but side-effects including nerve inflammation have been observed.
  
  
  OBJECTIVE
  To investigate the direct neurotoxic effects of BMP-2 and test the hypotheses that the use of BMP binding proteins, such as secreted phosphoprotein 24 kD (Spp24), can reduce or eliminate these effects.
  
  
  METHODS
  In vitro experiments and in vivo analysis in a rodent model.
  
  
  METHODS
  In vitro, dorsal root ganglion cells were cultured in the presence of BMP-2 with and without Spp24 and calcitonin gene-related peptide and Substance P, markers of neuroinflammation, were measured by immunohistochemistry. In vivo, rats underwent a left-sided laminotomy at L5 to expose the S1 nerve root and were randomized into four different groups according to the intervention at the laminotomy site: collagen sponge only (no BMP-2 or Spp24), BMP-2 in a collagen sponge only, BMP-2 in a collagen sponge+an empty collagen sponge to act as a barrier, and BMP-2 in a collagen sponge+Spp24 in a collagen sponge to act as a barrier. Functional evaluation was done using the Basso, Beattie, and Bresnahan scale and immunohistochemical analyses were performed using calcitonin gene-related peptide and Substance P staining.
  
  
  RESULTS
  The neuroinflammatory effects of BMP-2 in vitro were ameliorated by the addition of Spp24. Similarly, in vivo, Spp24 reduced the expression of markers on neuroinflammation in animals treated with BMP-2 and also improved the function after BMP-2 administration.
  
  
  CONCLUSIONS
  These results confirm that BMP binding proteins have great potential as adjuvant therapies to limit BMP-2 related side-effects in spine surgery.
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Changzheng Hospital, Second Military Medical University, 415 Fengyang Rd., Shanghai, 200003, P.R. China; Department of Orthopaedic Surgery, University of California, 675 Charles E. Young Dr. S., Los Angeles, CA 90024, USA. Electronic address: haijuntianmd@gmail.com.
authors.forename: Haijun
authors.initials: H
authors.lastname: Tian
authors.affiliation: Department of Orthodontics, Peking University School and Hospital of Stomatology, 22 South Zhongguancun St., Beijing 100081, P.R. China.
authors.forename: Chen-Shuang
authors.initials: CS
authors.lastname: Li
authors.affiliation: Department of Orthopaedic Surgery, University of California, 675 Charles E. Young Dr. S., Los Angeles, CA 90024, USA.
authors.forename: Trevor P
authors.initials: TP
authors.lastname: Scott
authors.affiliation: Department of Orthopaedic Surgery, University of California, 675 Charles E. Young Dr. S., Los Angeles, CA 90024, USA.
authors.forename: Scott R
authors.initials: SR
authors.lastname: Montgomery
authors.affiliation: Department of Orthopaedic Surgery, University of California, 675 Charles E. Young Dr. S., Los Angeles, CA 90024, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Phan
authors.affiliation: Department of Orthopaedic Surgery, University of California, 675 Charles E. Young Dr. S., Los Angeles, CA 90024, USA.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Lao
authors.affiliation: Department of Orthopaedic Surgery, University of California, 675 Charles E. Young Dr. S., Los Angeles, CA 90024, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedic Surgery, University of California, 675 Charles E. Young Dr. S., Los Angeles, CA 90024, USA.
authors.forename: Yawei
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Orthopaedic Surgery, University of California, 675 Charles E. Young Dr. S., Los Angeles, CA 90024, USA.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: Department of Orthopaedic Surgery, University of California, 675 Charles E. Young Dr. S., Los Angeles, CA 90024, USA.
authors.forename: Shinji
authors.initials: S
authors.lastname: Takahashi
authors.affiliation: Department of Orthopaedic Surgery, University of California, 675 Charles E. Young Dr. S., Los Angeles, CA 90024, USA.
authors.forename: Raed
authors.initials: R
authors.lastname: Alobaidaan
authors.affiliation: Department of Orthopaedic Surgery, University of California, 675 Charles E. Young Dr. S., Los Angeles, CA 90024, USA.
authors.forename: Monchai
authors.initials: M
authors.lastname: Ruangchainikom
authors.affiliation: Research Service, VA Greater Los Angeles Healthcare System, 16111 Plummer St., North Hills, CA 91343, USA.
authors.forename: Ke-Wei
authors.initials: KW
authors.lastname: Zhao
authors.affiliation: Research Service, VA Greater Los Angeles Healthcare System, 16111 Plummer St., North Hills, CA 91343, USA; Geriatric Research, Education and Clinical Center, VA Greater Los Angeles Healthcare System, 16111 Plummer St., North Hills, CA 91343, USA; Department of Medicine, University of California, 650 Charles E. Young Dr. S., Los Angeles, CA 90024, USA.
authors.forename: Elsa J
authors.initials: EJ
authors.lastname: Brochmann
authors.affiliation: Research Service, VA Greater Los Angeles Healthcare System, 16111 Plummer St., North Hills, CA 91343, USA; Geriatric Research, Education and Clinical Center, VA Greater Los Angeles Healthcare System, 16111 Plummer St., North Hills, CA 91343, USA; Department of Medicine, University of California, 650 Charles E. Young Dr. S., Los Angeles, CA 90024, USA.
authors.forename: Samuel S
authors.initials: SS
authors.lastname: Murray
authors.affiliation: Department of Orthopaedic Surgery, Keck School of Medicine of USC, 1520 San Pablo, HCT Suite 2000, Los Angeles, CA 90033, USA.
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Wang
authors.affiliation: Division of Orthopaedic Surgery, Department of Surgery, University of Nevada School of Medicine, 2040 W Charleston Blvd, Suite 601, Las Vegas, NV 89102, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Daubs
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2; D003094:Collagen / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000187:drug effects / Q000473:pathology; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D007796:Laminectomy; D008124:Locomotion / Q000187:drug effects; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D010750:Phosphoproteins / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D013126:Spinal Nerve Roots / Q000187:drug effects* / Q000473:pathology
chemical_list: D055396:Bone Morphogenetic Protein 2; D010750:Phosphoproteins; C091340:secreted phosphoprotein 24; D003094:Collagen
keywords: Bone morphogenetic protein-2; Complications; Nerve root inflammation; Posterior lumbar fusion; Secreted phosphoprotein 24 kD; Spine surgery