Disease relevance of Sost

• Our findings indicate that sclerostin plays an important role in bone remodeling and links bone resorption and bone apposition [1].

High impact information on Sost

• Although sclerostin shares some of the actions of the BMP antagonist noggin, we show here that it also has actions distinctly different from it [2].
• We show here that SOST/sclerostin is expressed exclusively by osteocytes in mouse and human bone and inhibits the differentiation and mineralization of murine preosteoblastic cells (KS483) [2].
• Its unique localization and action on osteoblasts suggest that sclerostin may be the previously proposed osteocyte-derived factor that is transported to osteoblasts at the bone surface and inhibits bone formation [2].
• Osteocyte control of bone formation via sclerostin, a novel BMP antagonist [3].
• Genomic deletion of a long-range bone enhancer misregulates sclerostin in Van Buchem disease [4].

Biological context of Sost

• Spaciotemporal association and bone morphogenetic protein regulation of sclerostin and osterix expression during embryonic osteogenesis [5].
• To understand the function of SOST in developmental skeletal tissue formation, we examined SOST gene expression in embryonic osteogenesis in vitro and in vivo [5].
• Strong expression in osteocytes suggested that sclerostin expressed by these central regulatory cells mediates bone homeostasis [3].
• Given the plethora of evidence indicating that canonical Wnt signaling stimulates osteogenesis, we believe that the high bone mass phenotype associated with the loss of sclerostin may be attributed, at least in part, to an increase in canonical Wnt signaling resulting from the reduction in sclerostin-mediated Wnt antagonism [6].
• Materials and Methods: DNA electroporation of calf muscle of mice using expression plasmids for BMP and sclerostin was used to study the effect of sclerostin on BMP-induced bone formation in vivo [7].

Anatomical context of Sost

• This effect was accompanied by a comparable reduction of sclerostin, the product of Sost, in osteocytes, as determined by quantitative immunoblot analysis of bone extracts and by immunostaining [8].
• We suggest that sclerostin negatively regulates the formation of bone by repressing the differentiation and/or function of osteoblasts induced by BMPs [1].
• Sclerostin-positive cells were identified as osteoclasts [1].
• Recombinant sclerostin protein produced in cultured cells was efficiently secreted as a monomer [1].

Associations of Sost with chemical compounds

• We compared and contrasted the mechanism of action for the cysteine knot protein subfamily, Wise and Sost (Sclerostin) [9].
• Wnt but Not BMP Signaling Is Involved in the Inhibitory Action of Sclerostin on BMP-Stimulated Bone Formation [7].

Other interactions of Sost

• Sclerostin is a novel secreted osteoclast-derived bone morphogenetic protein antagonist with unique ligand specificity [1].
• We show that recombinant sclerostin and noggin bound to each other with high affinity (K(D) = 2.92 nm) [10].

Analytical, diagnostic and therapeutic context of Sost

• Using BAC recombination and transgenesis, we characterized the expression of human sclerostin (SOST) from normal (SOST(wt)) or Van Buchem (SOST(vbDelta) alleles [4].
• Sost immunoprecipitation results were confirmed in vivo using cell culture [9].
• Epitope tagged cell supernatants containing either Sost or soluble mutant or wildtype LRP5/LRP6 were used for immunoprecipitation [9].

References