| Description | Growth and differentiation factor-5 (GDF-5) was initially identified in partially purified extracts from newborn calf articular cartilage. It is part of the bone morphogenetic protein (BMP) family of proteins, which are members of the TGF-β superfamily and plays a key role in skeletal development, bone formation, and stem cell differentiation. Human GDF-5 is highly homologous to its murine equivalent and the mature proteins differ only by one amino acid. GDF-5 belongs together with GDF-6 and GDF-7 to a subfamily of the BMPs. BMPs signal through heterotetrameric complex receptors, which include four type I receptors (ALK1, ALK2, ALK3, and ALK6) and three type II receptors (BMPRII, ActRIIA, and ActRIIB). GDF-5 binds specifically to BMPR1b, BMPRII, and ACTRIIA receptors forming a heterodimeric complex thus inducing the phosphorylation of smad1, 5, 8 and the translocation to the nucleus. GDF-5 enhances endochondral bone growth, development of limb skeletons and joints, and odontogenesis. GDF-5 stimulates osteogenic differentiation and increases VEGF levels in fat-derived stromal cells in vitro. Also, GDF-5 stimulates the proteoglycans and type II collagen production in intervertebral disc cells, and enhances cell proliferation and matrix synthesis in annulus fibrosus and nucleus pulposus cells, which inhibits degenerative disc disease. GDF-5 could be suitable for gene therapy for lumbar intervertebral disc degeneration. Mutations in the human GDF-5 gene result in a broad spectrum skeletal disorders. GDF-5 is a potent neurotrophic factor in vitro and in vivo for rat dopaminergic midbrain neurons, specifically the ones that degenerate in Parkinson's disease. Exogenous GDF-5 is neuroprotective in animal models of Parkinson’s disease. Moreover, it is a key regulator of the growth and elaboration of pyramidal cell dendrites in the developing hippocampus. |
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| Other Names | Bone morphogenetic protein 14 (BMP14), cartilage-derived morphogenetic protein 1 (CDMP1), BDA1C, Lipopolysaccharide associated protein 4 (LAP4), LPS associated protein 4, OS5, SYM1B, SYNS2, GDF5 |
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