Contrasting roles of leukemia inhibitory factor in murine bone development and remodeling involve region-specific changes in vascularization
Contrasting roles of leukemia inhibitory factor in murine bone development and remodeling involve region-specific changes in vascularization
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DOI：
10.1002/jbmr.1485
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发表时间：
2012-03-01
影响因子：
6.2
通讯作者：
Sims, Natalie A.
中科院分区：
文献类型：
--
作者：
Poulton, Ingrid J.;McGregor, Narelle E.;Sims, Natalie A.
我们在这里描述白血病抑制因子（LIF）在骨发育/生长和成人骨骼稳态的不同功能。在生长板和发育中的新生儿骨骼中，LIF缺乏增强了血管内皮生长因子（VEGF）水平，扩大了血管形成，并增加了巨大破骨细胞/破软骨细胞的形成，这些破骨细胞/破软骨细胞迅速破坏了生长板和发育中的新生儿骨骼的矿化区域。在此区域下方，成骨细胞形成大量的编织骨。相反，在成人骨重塑破骨细胞的形成不受LIF缺乏，而成骨细胞的形成和功能都显着受损，导致骨质减少。与LIF促进成骨细胞的承诺一致，增强骨髓脂肪细胞的形成也观察到在成年LIF空白小鼠，和小鼠基质细胞的脂肪细胞分化延迟LIF治疗。因此，LIF控制软骨向骨转变期间的血管大小和破骨细胞分化，而解剖学上独立的LIF依赖性途径调节骨重建中的成骨细胞和脂肪细胞承诺。(c)2012年美国骨与矿物质研究学会
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. (c) 2012 American Society for Bone and Mineral Research