Endocrine Abstracts

Sclerosteosis and van Buchem disease are closely related, rare sclerosing disorders characterized by substantial increase in bone mass of good quality which is due to increased bone formation. Both diseases have been linked to deficiency of the SOST gene product sclerostin, which in the adult is localized exclusively in osteocytes, the most abundant bone cell. In particular sclerostin is localized in mature osteocytes in mineralised cortical and cancellous bone, it inhi...

In light of the gender differences in bone geometry, sex steroids have been proposed as key regulators of pubertal periosteal bone formation. Sex steroids may affect periosteal bone apposition following activation of sex steroid receptors [androgen receptor (AR), estrogen receptor alpha (ERα) or beta (ERβ)]. Traditionally, it has been assumed that AR-mediated androgen action stimulates periosteal bone formation and thereby determines the larger bone size in males, wh...

Wnts are a large family of carbohydrate- and lipid-modified growth factors that mediate essential biological processes such as embryogenesis, morphogenesis and organogenesis. These proteins bind to a membrane receptor complex comprised of a frizzled (FZD) G-protein-coupled receptor and a low-density lipoprotein (LDL) receptor-related protein (LRP). The formation of this ligand-receptor complex initiates a number of signaling cascades that includes the canonical/beta-catenin pa...

Childhood hypothyroidism results in severely delayed skeletal development whereas adult thyrotoxicosis is associated with a 3–4 fold increase in osteoporotic fracture. To investigate molecular mechanisms underlying these abnormalities we characterized the skeletal phenotypes of mice harboring dominant negative mutations (TRα1PV/+, TRα1R384C/+, TRβPV/PV) or deletions (TRα0/0, TRβ−/−) of the genes encoding TRα and TRβ. Endochon...