Intermittent PTH stimulates periosteal bone formation by actions on post-mitotic preosteoblasts.
Intermittent PTH stimulates periosteal bone formation by actions on post-mitotic preosteoblasts.
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DOI：
10.1016/j.bone.2008.10.037
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发表时间：
2009-02
期刊：
影响因子：
4.1
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.;Ali, A. Afshan;Roberson, Paula K.;Weinstein, Robert S.;Manolagas, Stavros C.
间歇性给予甲状旁腺激素（PTH）通过增加成骨细胞的数量来刺激松质骨和骨膜骨表面的骨形成。我们之前对小鼠的研究表明，间歇性甲状旁腺激素至少在一定程度上通过减弱成骨细胞凋亡来增加松质成骨细胞的数量，但这种激素对骨膜骨的合成代谢作用的机制尚不清楚。我们报道，每天注射100 ng/g PTH（1-34）给4-6月龄小鼠，早在2天后，腰椎骨膜上的成骨细胞数量就增加了2 - 3倍。然而，在车辆处理的动物中，骨膜成骨细胞凋亡的发生率仅为0.2%，比松质成骨细胞低约20倍。此外，甲状旁腺素对骨膜成骨细胞凋亡没有明显的影响。无论在基础条件下还是在给予甲状旁腺激素后，给予BrdU 4天都不能标记骨膜成骨细胞。另一方面，在基础条件下标记松质成骨细胞，但PTH并没有增加brdu阳性细胞的百分比。因此，间歇性甲状旁腺激素不会通过刺激成骨细胞祖细胞的增殖来增加松质或骨膜成骨细胞的数量。与骨膜成骨细胞相比，松质成骨细胞的高周转率一致，在3.6kb大鼠Col1A1启动子的控制下，更昔洛韦诱导表达胸苷激酶的小鼠的复制成骨细胞祖细胞消融导致松质骨中的成骨细胞在7-14天内消失，而骨膜成骨细胞未受影响。然而，更昔洛韦治疗前14天可阻止PTH在骨膜骨上的合成代谢。我们得出结论，在松质骨中，PTH对成骨细胞凋亡的抑制增加了成骨细胞的数量，因为它们的凋亡率很高，使得这种激素的作用更深远。然而，在成骨细胞凋亡率低的骨膜骨中，甲状旁腺激素必须对有丝分裂后的前成骨细胞发挥促分化和/或促存活作用。靶向后一种细胞是增加骨膜成骨细胞数量的有效机制，在骨膜中，复制祖细胞的成骨细胞产生缓慢。
Intermittent administration of parathyroid hormone (PTH) stimulates bone formation on the surface of cancellous and periosteal bone by increasing the number of osteoblasts. Previous studies of ours in mice demonstrated that intermittent PTH increases cancellous osteoblast number at least in part by attenuating osteoblast apoptosis, but the mechanism responsible for the anabolic effect of the hormone on periosteal bone is unknown. We report that daily injections of 100 ng/g of PTH(1–34) to 4–6 month old mice increased the number of osteoblasts on the periosteum of lumbar vertebrae by 2–3 fold as early as after 2 days. However, the prevalence of apoptotic periosteal osteoblasts was only 0.2% in vehicle treated animals, which is ~20-fold lower than is the case for cancellous osteoblasts. Moreover, PTH did not have a discernable effect on periosteal osteoblast apoptosis. Administration of BrdU for 4 days failed to label periosteal osteoblasts under either basal conditions or following administration of PTH. Cancellous osteoblasts, on the other hand, were labeled under basal conditions, but PTH did not increase the percentage of BrdU-positive cells. Thus, intermittent PTH does not increase cancellous or periosteal osteoblast number by stimulating the proliferation of osteoblast progenitors. Consistent with high turnover of cancellous osteoblasts as compared to that of periosteal osteoblasts, ganciclovir-induced ablation of replicating osteoblast progenitors in mice expressing thymidine kinase under the control of the 3.6kb rat Col1A1 promoter resulted in disappearance of osteoblasts from cancellous bone over a 7–14 day period, whereas periosteal osteoblasts were unaffected. However, 14 days of pre-treatment with ganciclovir prevented PTH anabolism on periosteal bone. We conclude that in cancellous bone, attenuation of osteoblast apoptosis by PTH increases osteoblast number because their rate of apoptosis is high, making this effect of the hormone profound. However, in periosteal bone where the rate of osteoblast apoptosis is low, PTH must exert pro-differentiating and/or pro-survival effects on post-mitotic pre-osteoblasts. Targeting the latter cells is an effective mechanism for increasing osteoblast number in periosteal bone where the production of osteoblasts from replicating progenitors is slow.
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影响因子：
5.3
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