Secreted phosphoprotein 24 kD (Spp24) inhibits nerve root inflammation induced by bone morphogenetic protein-2.

Tian H, Li CS, Scott TP, Montgomery SR, Phan K, Lao L, Zhang W, Li Y, Hayashi T, Takahashi S, Alobaidaan R, Ruangchainikom M, Zhao KW4, Brochmann EJ, Murray SS, Wang JC, Daubs MD.
Source: Spine J
Publication Date: (2014)
Issue: 25: ePub
Research Area:
Basic Research
Cells used in publication:
Dorsal root gang. (DRG), rat
Species: rat
Tissue Origin: brain
BACKGROUND CONTEXT: BMP-2 has been used to successfully promote spine fusion, but side effect including nerve inflammation have been observed. PURPOSE: 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. STUDY DESIGN: 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 CGRP and Substance P, markers of neuro-inflammation, 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: 1) collagen sponge only (no BMP-2 or Spp24), 2) BMP-2 in a collagen sponge only, 3) BMP-2 in a collagen sponge + an empty collagen sponge to act as a barrier, 4) 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 was performed using CGRP and Substance P staining. This study was supported by a $25,000 grant from Cervical Spine Research Society, and all the disclosed conflict of interests should have no influence on the accuracy of the data being reported. RESULTS: The neuro-inflammatory effects of BMP-2 in vitro were ameliorated by the addition of Spp24. Similarly, in vivo, Spp24 reduced the expression of markers on neuro-inflammation in animals treated with BMP-2 and also improved 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.