The osteoclast differentiation factor osteoprotegerin-ligand is essential for mammary gland development - PubMed (original) (raw)

. 2000 Sep 29;103(1):41-50.

doi: 10.1016/s0092-8674(00)00103-3.

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

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The osteoclast differentiation factor osteoprotegerin-ligand is essential for mammary gland development

J E Fata et al. Cell. 2000.

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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.

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