Continuous elevation of PTH increases the number of osteoblasts via both osteoclast-dependent and -independent mechanisms.
Continuous elevation of PTH increases the number of osteoblasts via both osteoclast-dependent and -independent mechanisms.
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DOI：
10.1002/jbmr.145
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发表时间：
2010-11
影响因子：
6.2
通讯作者：
Manolagas, Stavros C.
中科院分区：
文献类型：
--
作者：
Jilka, Robert L.;O'Brien, Charles A.;Bartell, Shoshana M.;Weinstein, Robert S.;Manolagas, Stavros C.
持续的甲状旁腺激素（PTH）升高刺激骨重建（即，吸收和形成）。前者是RANKL合成增加的结果，但后者的原因尚未确定。目前的假说包括破骨细胞或骨基质在吸收过程中释放成骨细胞因子，调节成骨细胞谱系细胞的成骨细胞因子的产生和活性，以及增加血管生成。为了分析这些机制的作用，6月龄Swiss-Webster小鼠连续5天输注470 ng/h PTH（1-84）或525 ng/h可溶性RANKL（sRANKL）。这两种药物都增加了椎体松质骨中的破骨细胞和成骨细胞，但PTH治疗小鼠中成骨细胞与破骨细胞的比例和骨形成的增加更大。在接受PTH的小鼠中保持松质骨质量，但在接受sRANKL的小鼠中丢失，表明平衡重塑的维持需要破骨细胞介导的成骨细胞作用。与这一论点一致，PTH而不是sRANKL降低了Wnt拮抗剂sclerostin的水平，并增加了Wnt靶基因Nkd 2、Wisp 1和Twist 1的表达。此外，PTH而不是sRANKL增加了骨髓中的血管数量。在PTH输注前每周注射10 µg/g RANKL拮抗剂骨保护素2周，可消除破骨细胞和成骨细胞，并防止PTH诱导的破骨细胞、成骨细胞和血管增加。这些结果表明，PTH刺激破骨细胞依赖性以及破骨细胞非依赖性（Wnt信号传导）促成骨细胞生成途径，这两者都是松质骨中平衡的局灶性骨重建所需的。© 2010美国骨与矿物质研究学会。
Sustained parathyroid hormone (PTH) elevation stimulates bone remodeling (ie, both resorption and formation). The former results from increased RANKL synthesis, but the cause of the latter has not been established. Current hypotheses include release of osteoblastogenic factors from osteoclasts or from the bone matrix during resorption, modulation of the production and activity of osteoblastogenic factors from cells of the osteoblast lineage, and increased angiogenesis. To dissect the contribution of these mechanisms, 6-month-old Swiss-Webster mice were infused for 5 days with 470 ng/h PTH(1-84) or 525 ng/h soluble RANKL (sRANKL). Both agents increased osteoclasts and osteoblasts in vertebral cancellous bone, but the ratio of osteoblasts to osteoclasts and the increase in bone formation was greater in PTH-treated mice. Cancellous bone mass was maintained in mice receiving PTH but lost in mice receiving sRANKL, indicating that maintenance of balanced remodeling requires osteoblastogenic effects beyond those mediated by osteoclasts. Consistent with this contention, PTH, but not sRANKL, decreased the level of the Wnt antagonist sclerostin and increased the expression of the Wnt target genes Nkd2, Wisp1, and Twist1. Furthermore, PTH, but not sRANKL, increased the number of blood vessels in the bone marrow. Weekly injections of the RANKL antagonist osteoprotegerin at 10 µg/g for 2 weeks prior to PTH infusion eliminated osteoclasts and osteoblasts and prevented the PTH-induced increase in osteoclasts, osteoblasts, and blood vessels. These results indicate that PTH stimulates osteoclast-dependent as well as osteoclast-independent (Wnt signaling) pro-osteoblastogenic pathways, both of which are required for balanced focal bone remodeling in cancellous bone. © 2010 American Society for Bone and Mineral Research.
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影响因子：
4.1
作者：
Jilka, Robert L.;O'Brien, Charles A.;Ali, A. Afshan;Roberson, Paula K.;Weinstein, Robert S.;Manolagas, Stavros C.
通讯作者：
Manolagas, Stavros C.
影响因子：
20.3
作者：
Cackowski, Frank C.;Anderson, Judith L.;Roodman, G. David
通讯作者：
Roodman, G. David
影响因子：
56.9
作者：
He, TC;Sparks, AB;Kinzler, KW
通讯作者：
Kinzler, KW
影响因子：
6.2
作者：
Jilka, RL;Weinstein, RS;Manolagas, SC
通讯作者：
Manolagas, SC
影响因子：
4.1
作者：
Jackson, A;Vayssière, B;Rawadi, G
通讯作者：
Rawadi, G