Structure and biological function
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. Noggin is very highly conserved among vertebrates. Noggin predominanteley binds BMP-4 and BMP-2 and antagonizes their bioactivities by preventing binding to both type I and type II receptors.
Involvement in diseases:
- Ankylosing Spondylitis (Morbus Bechterew)
- Osteolytic Bone Metastases
- Pulmonary Arterial Hypertension
- Nonalcoholic fatty liver disease (NAFLD)
Noggin has been linked to this disease by cell culture experiments showing that the imbalance of NOGGIN and BMP-2 levels may be the underlying pathophysiological cause for the disease Imbalance Between Bone Morphogenetic Protein 2 and Noggin Induces Abnormal Osteogenic Differentiation of Mesenchymal Stem Cells in Ankylosing Spondylitis.Xie Z1 et al. Arthritis Rheumatol. 2016 Feb;68(2):430-40. doi: 10.1002/art.39433.
It has been shown, that osteolytic carcinoma derived cell lines constitutively secret NOGGIN. This gives rise to the idea, that NOGGIN has a crucial role in inhibiting bone repair by osteoblasts, thus facilitating the generation of osteolytic bone metastasis. The role of the BMP signaling antagonist noggin in the development of prostate cancer osteolytic bone metastasis. C Secondini et al. ,PLoS One, Jan 2011; 6(1): e16078.
Aside from its role in bone metabolism NOGGIN has a profound impact on the proliferation of arterial smooth muscle (ASMC) cells. A reduction of NOGGIN under hypoxia leads to significant increase of ASMC proliferation resulting in a narrowing of the vessel and thus creation of hypertonia. NOGGIN: a new therapeutic target for PH? Focus on “Noggin inhibits hypoxia-induced proliferation by targeting store-operated calcium entry and transient receptor potential cation channels” Olivier Boucherat and Sébastien Bonnet, Am J Physiol Cell Physiol. 2015 Jun 1; 308(11): C867–C868.
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. This has changed now: a recent study of Polyzos et al. using the high sensitivity FluoBolt™-NOGGIN assay could demonstrate, that the serum concentration of this biomarker is significantly reduced in patients 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 patients with NAFLD.Polyzos SA et al., Hormones (Athens)2018 Nov 22. doi: 10.1007/s42000-018-0083-8. [Epub ahead of print]
FluoBolt™-NOGGIN Super Sensitive and Easy
+ High sensitivity
+ Single step assay
+ No wash
+ No enzyme substrate
+ Stable Signal over Time