Noggin belongs to a group of diffusible proteins that bind to ligands of the TGF-beta family, and regulate their activity by inhibiting their access to signaling receptors. Noggin was originally identified as a BMP-4 antagonist whose action was critical for proper formation of the head and other dorsal structures. Consequently, noggin has been shown to modulate the activities of other BMPs including BMP-2,-7,-13, and -14. Targeted deletion of noggin in mice results in prenatal death, and a recessive phenotype displaying a severely malformed skeletal system. Conversely, transgenic mice over-expressing noggin in mature osteoblasts display impaired osteoblastic differentiation, reduced bone formation, and severe osteoporosis. Recombinant Murine Noggin is a 46.4 kDa disulfide-linked homodimer consisting of two 206 amino acid polypeptide chains.