St Vincent's Institute, 9 Princes St, Fitzroy, Victoria 3065, Australia.
J Bone Miner Res. 2012 Mar;27(3):586-95. doi: 10.1002/jbmr.1485.
We describe here distinct functions of leukemia inhibitory factor (LIF) in bone development/growth and adult skeletal homeostasis. In the growth plate and developing neonate bones, LIF deficiency enhanced vascular endothelial growth factor (VEGF) levels, enlarged blood vessel formation, and increased the formation of "giant" osteoclasts/chondroclasts that rapidly destroyed the mineralized regions of the growth plate and developing neonatal bone. Below this region, osteoblasts formed large quantities of woven bone. In contrast, in adult bone undergoing remodeling osteoclast formation was unaffected by LIF deficiency, whereas osteoblast formation and function were both significantly impaired, resulting in osteopenia. Consistent with LIF promoting osteoblast commitment, enhanced marrow adipocyte formation was also observed in adult LIF null mice, and adipocytic differentiation of murine stromal cells was delayed by LIF treatment. LIF, therefore, controls vascular size and osteoclast differentiation during the transition of cartilage to bone, whereas an anatomically separate LIF-dependent pathway regulates osteoblast and adipocyte commitment in bone remodeling.
我们在这里描述了白血病抑制因子 (LIF) 在骨骼发育/生长和成年骨骼稳态中的不同功能。在生长板和发育中的新生儿骨骼中，LIF 缺乏会增加血管内皮生长因子 (VEGF) 水平，扩大血管形成，并增加“巨大”破骨细胞/软骨细胞的形成，这些细胞会迅速破坏生长板和发育中的新生儿骨骼的矿化区域。在该区域下方，成骨细胞形成大量编织骨。相比之下，在正在进行重塑的成年骨骼中，LIF 缺乏对破骨细胞的形成没有影响，而成骨细胞的形成和功能都受到显著损害，导致骨质疏松症。与 LIF 促进成骨细胞分化一致，在成年 LIF 缺失小鼠中也观察到骨髓脂肪细胞形成增强，并且 LIF 处理延迟了小鼠基质细胞的脂肪细胞分化。因此，LIF 在软骨向骨骼过渡过程中控制血管大小和破骨细胞分化，而在骨骼重塑中存在解剖上分离的、依赖于 LIF 的途径来调节成骨细胞和脂肪细胞的分化。
