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首页> 外文期刊>Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research >Physiological functions of osteoblast lineage and T cell-derived RANKL in bone homeostasis
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Physiological functions of osteoblast lineage and T cell-derived RANKL in bone homeostasis

机译:成骨细胞谱系和T细胞衍生RANKL在骨稳态中的生理功能

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摘要

The cytokine RANKL is essential for osteoclast development in bone. The cellular sources of RANKL for support of osteoclast generation under various pathophysiological conditions have remained unclear, however. Here we show that inactivation of Rankl specifically in osteoblast lineage cells of mice with the use of an Osterix-Cre transgene results in typical osteopetrosis in the trabecular compartment of the tibia, with the phenotype being progressively less marked in the femur and vertebrae. In contrast to its effects on trabecular bone, RANKL deficiency in osteoblast lineage resulted in thinning of the femoral cortex in association with suppression of bone formation during the modeling process. Ablation of RANKL specifically in T cells resulted in a moderate but significant increase in tibial trabecular bone. Mice with RANKL deficiency in osteoblast lineage were protected from bone loss induced by ovariectomy as well as from joint destruction associated with arthritis, whereas loss of RANKL in T cells did not confer such protection. Finally, inducible deletion of Rankl selectively in the osteoblasts from 6 to 12 weeks of age resulted in an increase in bone mass in association with reduced bone resorption and formation. Our results thus suggest that RANKL produced by osteoblasts contributes to osteoclast development in vivo.
机译:RANKL细胞因子对于骨骼中破骨细胞的发育至关重要。然而,尚不清楚在各种病理生理条件下支持破骨细胞生成的RANKL的细胞来源。在这里,我们显示,使用Osterix-Cre转基因使小鼠的成骨细胞系中的Rankl失活会导致胫骨小梁区典型的骨质疏松症,其表型在股骨和椎骨中逐渐减少。与它对小梁骨的影响相反,成骨细胞谱系中的RANKL缺乏导致股骨皮层变薄,同时抑制了建模过程中的骨形成。 RANKL在T细胞中的特异性切除导致胫骨小梁的骨量适度但显着增加。成骨细胞谱系中具有RANKL缺乏的小鼠受到保护,免受卵巢切除术引起的骨质流失以及与关节炎相关的关节破坏,而T细胞中RANKL的丧失则不提供这种保护。最后,在6至12周龄的成骨细胞中选择性地诱导Rank1缺失,导致骨量增加与骨吸收和形成减少有关。因此,我们的结果表明由成骨细胞产生的RANKL有助于体内破骨细胞的发育。

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