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Nell-1 Protein Promotes Bone Formation in a Sheep Spinal Fusion Model

2010; Mary Ann Liebert, Inc.; Volume: 17; Issue: 7-8 Linguagem: Inglês

10.1089/ten.tea.2010.0486

1937-335X

Ronald K. Siu, Steven S. Lu, Weiming Li, Julie Whang, Gabriel McNeill, Xinli Zhang, Benjamin M. Wu, A. Simon Turner, Howard B. Seim, P. D. Hoang, Jeffrey C. Wang, Arthur A. Gertzman, Kang Ting, Chia Soo,

TGF-β signaling in diseases

Bone morphogenetic proteins (BMPs) are widely used as bone graft substitutes in spinal fusion, but are associated with numerous adverse effects. The growth factor Nel-like molecule-1 (Nell-1) is mechanistically distinct from BMPs and can minimize complications associated with BMP therapies. This study evaluates the efficacy of Nell-1 combined with demineralized bone matrix (DBM) as a novel bone graft material for interbody spine fusion using sheep, a phylogenetically advanced animal with biomechanical similarities to human spine. Nell-1+sheep DBM or Nell-1+heat-inactivated DBM (inDBM) (to determine the osteogenic effect of residual growth factors in DBM) were implanted in surgical sites as follows: (1) DBM only (control) (n=8); (2) DBM+0.3 mg/mL Nell-1 (n=8); (3) DBM+0.6 mg/mL Nell-1 (n=8); (4) inDBM only (control) (n=4); (5) inDBM+0.3 mg/mL Nell-1 (n=4); (6) inDBM+0.6 mg/mL Nell-1 (n=4). Fusion was assessed by computed tomography, microcomputed tomography, and histology. One hundred percent fusion was achieved by 3 months in the DBM+0.6 mg/mL Nell-1 group and by 4 months in the inDBM+0.6 mg/mL Nell-1 group; bone volume and mineral density were increased by 58% and 47%, respectively. These fusion rates are comparable to published reports on BMP-2 or autograft bone efficacy in sheep. Nell-1 is an independently potent osteogenic molecule that is efficacious and easily applied when combined with DBM.