Fata J E, Kong Y Y, Li J, Sasaki T, Irie-Sasaki J, Moorehead R A, Elliott R, Scully S, Voura E B, Lacey D L, Boyle W J, Khokha R, Penninger J M
Department of Medical Biophysics, Ontario Cancer Institute, University of Toronto, Canada.
Cell. 2000 Sep 29;103(1):41-50. doi: 10.1016/s0092-8674(00)00103-3.
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.
骨保护素配体（OPGL）是骨重塑所必需的关键破骨细胞分化/激活因子。我们报告称，缺乏OPGL或其受体RANK的小鼠在怀孕期间无法形成小叶-肺泡乳腺结构，导致新生小鼠死亡。对opgl-/-和rank-/-怀孕雌性小鼠进行的移植和OPGL拯救实验表明，OPGL直接作用于表达RANK的乳腺上皮细胞。OPGL的作用是上皮细胞自主性的。雌性opgl-/-小鼠的乳腺缺陷表现为小叶-肺泡芽中的细胞凋亡增强、增殖失败和PKB激活失败，而重组OPGL治疗可逆转这些缺陷。这些数据为乳腺发育提供了一种新的范例，并为女性骨质疏松症的激素调节和性别差异提供了进化依据。
