ATP6v0d2 deficiency increases bone mass, but does not influence ovariectomy-induced bone loss.
ATP6v0d2 deficiency increases bone mass, but does not influence ovariectomy-induced bone loss.
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DOI：
10.1016/j.bbrc.2010.10.117
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发表时间：
2010-12-03
影响因子：
3.1
通讯作者：
Lee SH
中科院分区：
文献类型：
--
作者：
Kim T;Ha H;Kim N;Park ES;Rho J;Kim EC;Lorenzo J;Choi Y;Lee SH
通过骨形成成骨细胞和骨吸收破骨细胞的平衡作用维持骨稳态。在病理条件下或随着年龄的增长，由于骨吸收增加，经常观察到过度的骨丢失。由于破骨细胞是机体中吸收骨的主要细胞，因此对破骨细胞命运的分子理解具有重要的临床意义。在过去的二十年里，许多分子球员，在正常发育过程中，破骨细胞分化的管理已被确定。然而，是否相同的分子调节病理条件下发生的骨丢失仍然在很大程度上未知。我们在这里报告，虽然ATP 6v 0 d2缺陷（ATP 6v 0 d2 KO）小鼠表现出骨硬化表型，由于破骨细胞成熟效率低下，这种缺陷未能保护小鼠卵巢切除术（OVX）诱导的骨丢失，绝经后相关的骨质疏松症的模型。此外，我们发现，在没有ATP 6v 0 d2的情况下，OVX诱导的骨髓细胞中的集落形成单位-粒细胞/巨噬细胞（CFU-GM）数量的增加和随后的体外破骨细胞形成不受影响。然而，即使在OVX后，在缺乏ATP 6v 0 d2的情况下，具有肌动蛋白环的大破骨细胞（直径> 100 μm）的形成仍然减少。两者合计，这些研究结果表明，ATP 6v 0 d2的关键作用可能仅限于控制正常发育下的骨稳态，而OVX诱导的骨丢失很可能主要是由破骨细胞前体的增加，而不是破骨细胞成熟的效率增加。
Bone homeostasis is maintained through the balanced action of bone-forming osteoblasts and bone-resorbing osteoclasts. Under pathological conditions or with age, excessive bone loss is often observed due to increased bone resorption. Since osteoclasts are the primary cells in the body that can resorb bone, molecular understanding of osteoclast fate has important clinical implications. Over the past twenty years, many molecular players that govern osteoclast differentiation during normal development have been identified. However, whether the same molecules regulate bone loss occurring under pathological conditions remains largely unknown. We report here that although ATP6v0d2-deficient (ATP6v0d2 KO) mice exhibit an osteopetrotic phenotype due to inefficient osteoclast maturation, this deficiency fails to protect mice from ovariectomy (OVX)-induced bone loss, a model for post-menopause-associated osteoporosis. Moreover, we show that an OVX-induced increase in the number of colony forming unit-granulocyte/macrophage (CFU-GM) in bone marrow cells and subsequent osteoclast formation in vitro was not affected in the absence of ATP6v0d2. However, even after OVX, formation of large osteoclasts (> 100 μm in diameter) with actin rings was still reduced in the absence of ATP6v0d2. Taken together, these findings suggest that the critical role of ATP6v0d2 may be limited to the control of bone homeostasis under normal development, and that OVX-induced bone loss is likely to be governed mostly by the increase in osteoclast precursors rather than increased efficiency of osteoclast maturation.
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影响因子：
30.8
作者：
Frattini, A;Orchard, PJ;Villa, A
通讯作者：
Villa, A
DOI：
10.1083/jcb.111.3.1305
发表时间：
1990-09
期刊：
The Journal of cell biology
影响因子：
--
作者：
Väänänen HK;Karhukorpi EK;Sundquist K;Wallmark B;Roininen I;Hentunen T;Tuukkanen J;Lakkakorpi P
通讯作者：
Lakkakorpi P
DOI：
10.1006/bbrc.1999.2042
发表时间：
2000-01-27
影响因子：
3.1
作者：
Menaa, C;Kurihara, N;Roodman, GD
通讯作者：
Roodman, GD
影响因子：
20.3
作者：
Riggs, BL;Khosla, S;Melton, LJ
通讯作者：
Melton, LJ
影响因子：
15.9
作者：
Lean, JM;Davies, JT;Chambers, TJ
通讯作者：
Chambers, TJ