|Detection of Human SOST/Sclerostin by Western Blot. Western blot shows lysates of human cartilage tissue and human bone marrow. PVDF membrane was probed with 2 µg/mL of Goat Anti-Human SOST/Sclerostin Antigen Affinity-purified Polyclonal Antibody (Catalog # AF1406) followed by HRP-conjugated Anti-Goat IgG Secondary Antibody (Catalog # HAF017). A specific band was detected for SOST/Sclerostin at approximately 28 kDa (as indicated). This experiment was conducted under reducing conditions and using Immunoblot Buffer Group 1.|
SOST, also known as sclerostin, is a member of the cerberus/DAN family, a group of secreted glycoproteins characterized by a cysteine-knot motif. Cerberus/DAN family members are putative BMP antagonists, and include Dan, Cerberus, Gremlin, PRDC, and Caronte. While the overall sequence identity between members of the family is low, they have conserved spacing of six cysteine residues. Cerberus and dan have an additional cysteine residue used for dimerization; however, SOST does not and is secreted as a monomer. SOST was originally identified as an important regulator of bone homesotasis. Positional cloning studies identified that mutations in the SOST gene can cause sclerosteosis and van Buchem disease, bone dysplasia disorders characterized by progressive skeletal overgrowth. Significant levels of SOST expression are detected in bone, cartilage, kidney, and liver. SOST is expressed by osteoclasts in developing bones of mouse embryos, including both intramembranously forming skull bones and endochondrally forming long bones. SOST plays a physiological role as a negative regulator of bone formation by repressing BMP-induced osteogenesis. SOST has been shown to have unique ligand specificity, binding BMP-5, -6, and -7 with high affinity and BMP-2 and -4 with low affinity. This seems to be the first example of a BMP antagonist being localized to osteoclasts, cells derived from the hematopoietic lineage, that function to degrade bone matrix. Human and mouse SOST share 88% amino acid identity (1-3).
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