Author/Authors :
Jimmie E Fata، نويسنده , , Young-Yun Kong، نويسنده , , Ji Li، نويسنده , , Takehiko Sasaki، نويسنده , , Junko Irie-Sasaki، نويسنده , , Roger A Moorehead، نويسنده , , Robin Elliott، نويسنده , , Sheila Scully، نويسنده , , Evelyn B Voura، نويسنده , , David L. Lacey، نويسنده , , William E. Boyle Jr.، نويسنده , , Rama Khokha، نويسنده , , Josef M. Penninger، نويسنده ,
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.
