| Literature DB >> 11051546 |
J E Fata1, Y Y Kong, J Li, T Sasaki, J Irie-Sasaki, R A Moorehead, R Elliott, S Scully, E B Voura, D L Lacey, W J Boyle, R Khokha, J M Penninger.
Abstract
Osteoprotegerin-ligand (OPGL) is a key osteoclast differentiation/activation factor essential for bone remodeling. We report that mice lacking OPGL or its receptor RANK fail to form lobulo-alveolar mammary structures during pregnancy, resulting in death of newborns. Transplantation and OPGL-rescue experiments in opgl-/- and rank-/- pregnant females showed that OPGL acts directly on RANK-expressing mammary epithelial cells. The effects of OPGL are autonomous to epithelial cells. The mammary gland defect in female opgl-/- mice is characterized by enhanced apoptosis and failures in proliferation and PKB activation in lobulo-alveolar buds that can be reversed by recombinant OPGL treatment. These data provide a novel paradigm in mammary gland development and an evolutionary rationale for hormonal regulation and gender bias of osteoporosis in females.Entities:
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Year: 2000 PMID： 11051546 DOI： 10.1016/s0092-8674(00)00103-3
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582