Binding to COMP reduces the BMP2 dose for spinal fusion in a rat model

Motasem Refaat, Eric Otto Klineberg, Michael C. Fong, Tanya C. Garcia, Jonathan K Leach, Dominik R Haudenschild

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Study Design. The aim of this study is to test the effect of cartilage oligomeric matrix protein (COMP) on enhancing rhBMP-2 induced spinal fusion in a prospective 8-week interventional trial of spinal fusion in rats. Objective. To determine whether the amount of bone morphogenetic protein-2 (BMP-2) required to achieve spinal fusion in a pre-clinical model can be reduced by the addition of COMP. Summary of Background Data. BMPs are applied clinically at supraphysiological doses to promote spinal fusion by inducing osseous growth, but dose-related limitations include ectopic bone formation and local inflammatory reactions. COMP is a matricellular BMP-binding protein expressed during endochondral ossification and fracture healing. In vitro studies demonstrate enhanced activity of BMP bound to COMP. We hypothesized that BMP bound to COMP could achieve equivalent spinal fusion rates at lower doses and with fewer complications. Methods. Posterolateral intertransverse process spinal fusion at L4 to L5 was performed in 36 Lewis rats. COMP (10μg) was tested with or without "low-dose" rhBMP-2 (2μg), and the results were compared with the "low-dose" (2μg rhBMP-2) and "high-dose" (10μg rhBMP-2) groups. All groups utilized insoluble collagen bone matrix carrier (ICBM). Fusion was evaluated by radiology, histology, and manual palpation. BMP release kinetics were evaluated in vitro. Results. Fusion grading of microCT images demonstrated that the fusion rate with the COMP+LoBMP was statistically equivalent to HiBMP, and significantly better than LoBMP without COMP. These results were confirmed with radiographs and manual palpation. BMP release kinetics suggest that COMP increased local concentrations of BMP due to decreased growth factor retention on the scaffold. Conclusion. COMP enhances BMP-induced bone formation, enabling lower doses of BMP to achieve the same level of spinal fusion. COMP may function by affecting the availability and biological presentation of BMP-2. A decrease of BMP-2 required for fusion may reduce dose-related adverse effects, surgical costs, and improve clinical outcomes.

Original languageEnglish (US)
Pages (from-to)E829-E836
JournalSpine
Volume41
Issue number14
DOIs
StatePublished - Jul 15 2016

Fingerprint

Cartilage Oligomeric Matrix Protein
Spinal Fusion
Bone Morphogenetic Protein 2
Osteogenesis
Palpation
X-Ray Microtomography
Bone Matrix
Fracture Healing
Radiology
Biological Availability
Intercellular Signaling Peptides and Proteins
Histology

Keywords

  • bone formation
  • bone morphogenetic matrix protein-2
  • cartilage oligomeric matrix protein
  • dose reduction
  • extracellular matrix proteins
  • growth factor delivery
  • INFuse
  • matricellular protein
  • rat model
  • spinal fusion

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Clinical Neurology

Cite this

Binding to COMP reduces the BMP2 dose for spinal fusion in a rat model. / Refaat, Motasem; Klineberg, Eric Otto; Fong, Michael C.; Garcia, Tanya C.; Leach, Jonathan K; Haudenschild, Dominik R.

In: Spine, Vol. 41, No. 14, 15.07.2016, p. E829-E836.

Research output: Contribution to journalArticle

Refaat, Motasem ; Klineberg, Eric Otto ; Fong, Michael C. ; Garcia, Tanya C. ; Leach, Jonathan K ; Haudenschild, Dominik R. / Binding to COMP reduces the BMP2 dose for spinal fusion in a rat model. In: Spine. 2016 ; Vol. 41, No. 14. pp. E829-E836.
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AU - Klineberg, Eric Otto

AU - Fong, Michael C.

AU - Garcia, Tanya C.

AU - Leach, Jonathan K

AU - Haudenschild, Dominik R

PY - 2016/7/15

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N2 - Study Design. The aim of this study is to test the effect of cartilage oligomeric matrix protein (COMP) on enhancing rhBMP-2 induced spinal fusion in a prospective 8-week interventional trial of spinal fusion in rats. Objective. To determine whether the amount of bone morphogenetic protein-2 (BMP-2) required to achieve spinal fusion in a pre-clinical model can be reduced by the addition of COMP. Summary of Background Data. BMPs are applied clinically at supraphysiological doses to promote spinal fusion by inducing osseous growth, but dose-related limitations include ectopic bone formation and local inflammatory reactions. COMP is a matricellular BMP-binding protein expressed during endochondral ossification and fracture healing. In vitro studies demonstrate enhanced activity of BMP bound to COMP. We hypothesized that BMP bound to COMP could achieve equivalent spinal fusion rates at lower doses and with fewer complications. Methods. Posterolateral intertransverse process spinal fusion at L4 to L5 was performed in 36 Lewis rats. COMP (10μg) was tested with or without "low-dose" rhBMP-2 (2μg), and the results were compared with the "low-dose" (2μg rhBMP-2) and "high-dose" (10μg rhBMP-2) groups. All groups utilized insoluble collagen bone matrix carrier (ICBM). Fusion was evaluated by radiology, histology, and manual palpation. BMP release kinetics were evaluated in vitro. Results. Fusion grading of microCT images demonstrated that the fusion rate with the COMP+LoBMP was statistically equivalent to HiBMP, and significantly better than LoBMP without COMP. These results were confirmed with radiographs and manual palpation. BMP release kinetics suggest that COMP increased local concentrations of BMP due to decreased growth factor retention on the scaffold. Conclusion. COMP enhances BMP-induced bone formation, enabling lower doses of BMP to achieve the same level of spinal fusion. COMP may function by affecting the availability and biological presentation of BMP-2. A decrease of BMP-2 required for fusion may reduce dose-related adverse effects, surgical costs, and improve clinical outcomes.

AB - Study Design. The aim of this study is to test the effect of cartilage oligomeric matrix protein (COMP) on enhancing rhBMP-2 induced spinal fusion in a prospective 8-week interventional trial of spinal fusion in rats. Objective. To determine whether the amount of bone morphogenetic protein-2 (BMP-2) required to achieve spinal fusion in a pre-clinical model can be reduced by the addition of COMP. Summary of Background Data. BMPs are applied clinically at supraphysiological doses to promote spinal fusion by inducing osseous growth, but dose-related limitations include ectopic bone formation and local inflammatory reactions. COMP is a matricellular BMP-binding protein expressed during endochondral ossification and fracture healing. In vitro studies demonstrate enhanced activity of BMP bound to COMP. We hypothesized that BMP bound to COMP could achieve equivalent spinal fusion rates at lower doses and with fewer complications. Methods. Posterolateral intertransverse process spinal fusion at L4 to L5 was performed in 36 Lewis rats. COMP (10μg) was tested with or without "low-dose" rhBMP-2 (2μg), and the results were compared with the "low-dose" (2μg rhBMP-2) and "high-dose" (10μg rhBMP-2) groups. All groups utilized insoluble collagen bone matrix carrier (ICBM). Fusion was evaluated by radiology, histology, and manual palpation. BMP release kinetics were evaluated in vitro. Results. Fusion grading of microCT images demonstrated that the fusion rate with the COMP+LoBMP was statistically equivalent to HiBMP, and significantly better than LoBMP without COMP. These results were confirmed with radiographs and manual palpation. BMP release kinetics suggest that COMP increased local concentrations of BMP due to decreased growth factor retention on the scaffold. Conclusion. COMP enhances BMP-induced bone formation, enabling lower doses of BMP to achieve the same level of spinal fusion. COMP may function by affecting the availability and biological presentation of BMP-2. A decrease of BMP-2 required for fusion may reduce dose-related adverse effects, surgical costs, and improve clinical outcomes.

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KW - spinal fusion

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