Investigational growth factors utilized in animal models of spinal fusion: Systematic review

Table 2 Normal biological activity of each included growth factor

Growth factors	Normal biologic activity[16-31]
AB204	Chimera of activin A and BMP-2 - which are both members of the transforming growth factor-beta (TGF-beta) superfamily
Ang-1	Pro-angiogenic growth factor that mediates reciprocal interactions between the endothelium and surrounding matrix, inhibits endothelial permeability, and contributes to blood vessel maturation and stability
Calcitonin	Secreted by the parafollicular (C cells) of the thyroid gland and is a direct inhibitor of osteoclasts
EPO	Produced in the kidney in response to hypoxia and is a well-known growth factor essential for hematopoiesis
bFGF	Broad mitogenic and angiogenic functions and is important for limb and nervous system development, wound healing, and tumor growth
GDF-5	Structurally similar to BMP-2 and BMP-7, GDF-5 is a secreted member of the TGF-beta superfamily of proteins involved in the development of various tissues and cell types, as well as the growth of neuronal axons and dendrites
IGF-1/TGF-beta	IGF-1 is a protein with similar structure and function to insulin involved in mediating growth and development. TGF-beta 3 is a secreted ligand capable of binding to various TGF-beta receptors involved in embryogenesis and cell differentiation and may play a role in wound healing
Insulin	A product of post-translational modification of proinsulin, involved in intracellular glucose uptake
NELL-1	Secreted protein containing epidermal growth factor-like repeats. It binds to the cell surface heterodimer integrin α3β1, resulting in intracellular changes that induce osteoblastogenic programming. Its overexpression is associated with craniosynostosis
Noggin	Secreted polypeptide which binds and inactivates members of the transforming growth factor-beta superfamily of proteins. Noggin is important for developmental process such neural tube closure and joint formation, and when mutated can lead to proximal symphalangism and multiple synostoses syndrome
P-15	Synthetic 15-amino acid peptide with an identical sequence to the cell-binding domain found on the α1(I) chain of Type-I collagen. It is combined with an anorganic bovine-derived hydroxyapatite matrix (ABM) to produce an osteoinductive and osteoconductive bone graft alternative
Peptide B2A	Synthetic, receptor-targeted peptide that cooperatively enhances biologic BMP-2 response
SPP24	Secreted bone matrix protein that belongs to the cystatin superfamily and binds proteins in the transforming growth factor-beta family of cytokines

BMP: Bone morphogenetic protein; GDF: Growth differentiation factor; TGF: Transforming growth factor; IGF: Insulin-like growth factor.