Noggin is a secreted homodimeric glycoprotein that is an antagonist of bone morphogenetic proteins (BMPs). Human Noggin cDNA encodes a 232 amino acid (aa) precursor protein; cleavage of a 19 aa signal peptide generates the 213 aa mature protein which contains an N terminal acidic region, a central basic heparin binding segment and a C terminal cysteine knot structure. Secreted Noggin probably remains close to the cell surface due to its binding of heparin containing proteoglycans. Noggin is very highly conserved among vertebrates.
Noggin predominantly binds BMP–4 and BMP–2 and antagonizes their bioactivities by preventing binding to both type I and type II receptors. During embryogenesis Noggin is a crucial factor for regulation of various developmental processes like formation of neural tubes, cardiomyocyte growth and patterning as well as skeletal development where Noggin prevents chondrocyte hyperplasia, thus allowing proper formation of joints. Mutations within the cysteine–knot region of human Noggin are linked to multiple types of skeletal dysplasias that result in apical joint fusions. Noggin is expressed in defined areas of the adult central nervous system and peripheral tissues such as lung, skeletal muscle and skin.
In adults Noggin may be associated with dissemination of tumor cells to bone, ankylosing spondylitis or pulmonary arterial hypertension (PAH). Its value as biomarker remains to be established yet.
Ankylosing Spondylitis (Morbus Bechterew)
Cell culture experiments have shown that the imbalance of Noggin and BMP-2 levels may be the underlying pathophysiological cause for the imbalance between bone morphogenetic protein 2 and Noggin induces abnormal osteogenic differentiation of mesenchymal stem cells in Ankylosing Spondylitis.
Osteolytic Bone Metastases
It has been shown, that osteolytic carcinoma derived cell lines constitutively secret Noggin. This gives rise to research whether Noggin plays a crucial role in inhibiting bone repair by osteoblasts, thus facilitating the generation of osteolytic bone metastasis.
Pulmonary Arterial Hypertension
Aside from its role in bone metabolism Noggin has a profound impact on the proliferation of arterial smooth muscle (ASMC) cells. Researchers may study how a reduction of Noggin under hypoxia may lead to significant increase of ASMC proliferation resulting in a narrowing of the vessel and thus creation of hypertonia.
Nonalcoholic Fatty Liver Disease (NAFLD)
Nonalcoholic fatty liver disease (NAFLD) which may advance to cirrhosis and hepatocellular carcinoma is among the most common chronic liver diseases and affects globally approximately one fourth to one third of the general population worldwide. However, so far no biomarkers existed for non-invasive studies of this disease. A recent study using the high sensitivity FluoBolt™ Noggin assay could demonstrate, that the serum concentration of this biomarker is significantly reduced in subjects with NAFLD and approaches normal levels of healthy persons under vitamin E and spironolactone treatment. At present the FluoBolt™ Noggin assay is the only tool available for such investigations in subjects with NAFLD.