PROSTAGLANDIN-E2 STIMULATES INSULIN-LIKE GROWTH FACTOR-I SYNTHESIS IN OSTEOBLAST-ENRICHED CULTURES FROM FETAL-RAT BONE
PROSTAGLANDIN-E2 STIMULATES INSULIN-LIKE GROWTH FACTOR-I SYNTHESIS IN OSTEOBLAST-ENRICHED CULTURES FROM FETAL-RAT BONE
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DOI：
10.1210/endo-128-6-2895
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发表时间：
1991-06-01
期刊：
影响因子：
4.8
通讯作者：
CANALIS, E
中科院分区：
文献类型：
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作者：
MCCARTHY, TL;CENTRELLA, M;CANALIS, E
前列腺素 E2 (PGE2) 影响骨吸收和形成，但其作用机制尚不清楚。 已知 PGE2 可提高多种培养系统中的细胞内 cAMP 水平。 在富含成骨细胞 (Ob) 的原代培养物中增加 cAMP 的药物可增强骨骼胰岛素样生长因子 I (IGF-I) 的合成，IGF-I 是一种有效的骨合成代谢因子。 暴露于 0.01-1-mu-M 的 PGE2 5 分钟，Ob 培养物中的 cAMP 合成增强了 8 至 54 倍，并且在 6 小时内，稳态前原 IGF-I 转录物增加了 3 倍。 PGE2 对 IGF-I 信使 RNA 的刺激作用在治疗后 4 小时内首次显现出来，并在至少 24 小时内保持较高水平。 此外，0.01-1-mu-M PGE2 使免疫反应性IGF-I多肽积累增加1.9至4.7倍。 相反，PGE2 在此时间范围内没有升高稳态 IGF-II mRNA 或多肽水平。 虽然PTH增加骨细胞的cAMP、细胞内钙和PGE2的产生，但我们之前的研究表明PTH对IGF-I产生的刺激作用是cAMP，而不是钙依赖性的。 通过暴露于吲哚美辛抑制 PGE2 合成不会改变基础或 PTH 刺激的 IGF-I 水平，证实 PTH 对 IGF-I 的作用不依赖于 PGE2。 这些研究表明，PGE2 的产生是许多增强骨吸收药物的共同特征，通过其增加 cAMP 的能力，从而增加成骨细胞合成 IGF-I 的能力，可能有助于骨吸收和新骨形成的耦合。
Prostaglandin E2 (PGE2) affects both bone resorption and formation, but its mechanism of action remains unclear. PGE2 is known to elevate intracellular cAMP levels in a variety of culture systems. Agents that increase cAMP in primary osteoblast-enriched (Ob) cultures enhance the synthesis of skeletal insulin-like growth factor I (IGF-I), a potent anabolic factor for bone. A 5 min exposure to PGE2 at 0.01-1-mu-M enhanced cAMP synthesis in Ob cultures by 8- to 54-fold, and within 6 h produced up to a 3- fold increase in steady state prepro-IGF-I transcripts. The stimulatory effect of PGE2 on IGF-I messenger RNA was first evident within 4 h of treatment and remained elevated for at least 24 h. Furthermore, 0.01-1-mu-M PGE2 increased immunoreactive IGF-I polypeptide accumulation by 1.9 to 4.7-fold. In contrast PGE2 did not elevate steady state IGF-II mRNA or polypeptide levels within this time frame. Although PTH increases cAMP, intracellular calcium, and PGE2 production by bone cells, our previous studies indicate that the stimulatory effect of PTH on IGF-I production is cAMP, but not calcium dependent. Inhibition of PGE2 synthesis by exposure to indomethacin did not alter basal or PTH-stimulated IGF-I levels, substantiating that the effect of PTH on IGF-I is not PGE2 dependent. These studies indicate that PGE2 production, a feature common to many agents that enhance bone resorption, could contribute to the coupling of bone resorption and new bone formation, by way of its ability to increase cAMP and, consequently, IGF-I synthesis by the osteoblast.