Nell-1 protein promotes bone formation in a sheep spinal fusion model.
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.
Dental and Craniofacial Research Institute, School of Medicine, University of California, Los Angeles, California 90095-1579, USA.
Ronald K
RK
Siu
Steven S
SS
Lu
Weiming
W
Li
Julie
J
Whang
Gabriel
G
McNeill
Xinli
X
Zhang
Benjamin M
BM
Wu
A Simon
AS
Turner
Howard B
HB
Seim
Paul
P
Hoang
Jeffrey C
JC
Wang
Arthur A
AA
Gertzman
Kang
K
Ting
Chia
C
Soo
D000818:Animals; D005260:Female; D020342:Finite Element Analysis; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010012:Osteogenesis / Q000502:physiology*; D011859:Radiography; D012756:Sheep; D013123:Spinal Fusion / Q000379:methods*; D013131:Spine / Q000000981:diagnostic imaging / Q000601:surgery
D009419:Nerve Tissue Proteins