Systemic administration of an anabolic dose of PGE2 in young rats increases the osteogenic capacity of bone marrow.
Systemic administration of an anabolic dose of PGE2 in young rats increases the osteogenic capacity of bone marrow.
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DOI：
10.1016/s8756-3282(97)00033-1
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发表时间：
1997-06
期刊：
影响因子：
4.1
通讯作者：
M. Weinreb;I. Suponitzky;S. Keila
中科院分区：
文献类型：
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作者：
M. Weinreb;I. Suponitzky;S. Keila
前列腺素E2（PGE 2）在全身给药时具有显著的合成代谢特性（即，它增加骨形成，并因此增加骨量）。最近，我们对幼鼠给予6 mg/kg PGE 2 3周的效果进行了表征，结果表明，PGE 2可增加皮质骨和松质骨的骨量、长骨的机械强度和颅骨的骨密度。我们还发现，一个单一剂量的PGE 2诱导早期反应基因（c-fos，c-jun，和p-l）在这两种类型的骨骨髓细胞的表达。这些观察结果，以及其他人在PGE 2治疗的动物中新的松质骨形成的发现，表明成骨细胞从其前体中的募集是PGE 2合成代谢作用的主要机制。为了直接验证这一假设，我们将PGE 2（6 mg/kg）或溶剂注射到4周龄大鼠体内2周，然后在体外培养系统中评估骨髓的成骨潜力。在β-甘油磷酸盐、抗坏血酸盐和地塞米松存在下建立原代和第一代骨髓培养物，通过骨结节形成和碱性磷酸酶活性测量成骨分化。该方案使骨量（表示为股骨灰重）增加4.7%，胫骨松质骨面积增加38.3%。尽管接种了相同数量的骨髓细胞，但PGE 2治疗大鼠的原代和第一代培养物在21天时的坏死因子形成增加。碱性磷酸酶活性升高，在原代和第一代培养物从前列腺素E2治疗的大鼠开始培养后6-10天开始。在PGE 2处理的大鼠培养物中，细胞增殖仅略有升高。这些数据有力地表明，体内给予PGE 2诱导骨髓中骨祖细胞的增殖或分化，并且这种作用在其体内合成代谢作用中起主要作用。
Prostaglandin E2(PGE2) possesses significant anabolic properties when administered systemically (i.e., it increases bone formation and, consequently, bone mass). We recently characterized the effects of a 3 week administration of 6 mg/kg PGE2into young rats and showed it increases cortical and cancellous bone mass and mechanical strength in long bones and bone density in the calvaria. We also found that a single dose of PGE2induces the expression of early-response genes (c-fos, c-jun, and egr-1) in bone marrow cells within these two types of bone. These observations, together with findings by others of new cancellous bone formation in PGE2-treated animals, suggested that recruitment of osteoblasts from their precursors is a major mechanism of the anabolic effect of PGE2. To test this hypothesis directly, we injected PGE2(6 mg/kg) or vehicle into 4-week-old rats for 2 weeks and then assessed the osteogenic potential of bone marrow in an ex vivo culture system. Primary and first-passage bone marrow cultures were established in the presence of β-glycerophosphate, ascorbate, and dexamethasone, and osteogenic differentiation was measured by bone nodule formation and alkaline phosphatase activity. This regimen increased bone mass expressed as femoral ash weight by 4.7% and tibial cancellous bone area by 38.3%. Nodule formation at 21 days was increased in both primary and first-passage cultures from PGE2-treated rats despite seeding of the same number of marrow cells. Alkaline phosphatase activity was elevated in both primary and first-passage cultures from PGE2-treated rats beginning 6–10 days after culture initiation. Cell proliferation was only slightly elevated in cultures from PGE2-treated rats. These data strongly suggest that in vivo administration of PGE2induces the proliferation or differentiation of osteoprogenitor cells in bone marrow, and this effect takes a major part in its anabolic effect in vivo.