Effects of basic fibroblast growth factor and a prostaglandin E2 receptor subtype 4 agonist on osteoblastogenesis and adipogenesis in aged ovariectomized rats
Effects of basic fibroblast growth factor and a prostaglandin E2 receptor subtype 4 agonist on osteoblastogenesis and adipogenesis in aged ovariectomized rats
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DOI：
10.1359/jbmr.070313
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发表时间：
2007-06-01
影响因子：
6.2
通讯作者：
Wronski, Thomas J.
中科院分区：
文献类型：
--
作者：
Aguirre, J. Ignacio;Leal, Martha E.;Wronski, Thomas J.
碱性成纤维细胞生长因子刺激骨和脂肪生成同时在骨骼网站与红色，但不与脂肪骨髓，而前列腺素E（2）受体亚型4激动剂有骨合成代谢的影响，在这两个骨骼网站和减少脂肪组织内的红色和脂肪marrow.Introduction：碱性成纤维细胞生长因子（bFGF）刺激骨生成在骨骼网站与造血，但不与脂肪骨髓。前列腺素E-2（PGE（2））受体亚型4激动剂（EP 4A）刺激前骨骼部位的骨生成，但其对脂肪骨髓部位的影响尚不清楚。此外，bFGF和PGE（2）通过EP 4受体也参与脂肪形成。然而，它们对骨髓脂肪形成的具体影响和与成骨的相互关系从来没有被研究在vivo.Materials和方法：雌性Sprague-Dawley大鼠卵巢切除（OVX）或假手术，并维持1年后手术。OVX大鼠每天皮下注射bFGF或EP 4A，持续3周。这些药物的成骨和成脂作用通过组织形态计量学和通过实时PCR测定腰椎和尾椎（造血和脂肪骨髓占优势的骨骼）中与这些事件相关的基因表达变化进行评估。FGFR 1 -4和EP 4受体的表达也进行了评估，通过实时PCR和免疫cytochemistic.Results：bFGF和EP 4A刺激骨形成的骨骼网站与造血骨髓，但只有后来的合成代谢剂也是有效的脂肪骨髓网站。碱性成纤维细胞生长因子在脂肪骨髓部位的骨合成代谢作用减弱不是由于该部位缺乏生长因子的细胞表面受体所致。有趣的是，EP 4A减少了脂肪骨髓面积和脂肪细胞的数量，而bFGF增加了骨髓内的骨生成和脂肪生成。结论：bFGF可同时促进红骨髓部位的成骨和骨髓脂肪形成，但不能促进脂肪骨髓部位的成骨和脂肪形成。相比之下，EP 4A刺激骨骼部位的骨形成，具有造血和脂肪骨髓，同时减少脂肪骨髓面积和骨髓中脂肪细胞的数量，这表明骨生成是以脂肪生成为代价的。
bFGF stimulates osteo- and adipogenesis concurrently at skeletal sites with red but not with fatty marrow, whereas a PGE(2) receptor subtype 4 agonist has bone anabolic effects at both skeletal sites and decreases adipose tissue within red and fatty marrow.Introduction: Basic fibroblast growth factor (bFGF) stimulates osteogenesis at skeletal sites with hematopoietic but not with fatty marrow. The prostaglandin E-2 (PGE(2)) receptor subtype 4 agonist (EP4A) stimulates osteogenesis at the former skeletal sites, but its effects at fatty marrow sites are unknown. In addition, both bFGF and PGE(2) through the EP4 receptor have also been implicated in adipogenesis. However, their specific effects on bone marrow adipogenesis and the inter-relationship with osteogenesis have never been studied in vivo.Materials and Methods: Female Sprague-Dawley rats were ovariectomized (OVX) or sham-operated and maintained for 1 yr after surgery. OVX rats were then injected daily with bFGF or with EP4A SC for 3 wk. The osteo- and adipogenic effects of these agents were assessed by histomorphometry and by determining changes in expression of genes associated with these events by real-time PCR in the lumbar and caudal vertebrae, bones with a predominance of hematopoietic and fatty marrow, respectively. Expression of FGFR1-4 and the EP4 receptor were also evaluated by real-time PCR and immunocytochemistry.Results: bFGF and EP4A stimulated bone formation at skeletal sites with hematopoietic marrow, but only the later anabolic agent is also effective at fatty marrow sites. The diminished bone anabolic effect of bFGF at the fatty marrow site was not caused by a lack of cell surface receptors for the growth factor at this site. Interestingly, whereas EP4A decreased fatty marrow area and the number of adipocytes, bFGF increased osteogenesis and adipogenesis within the bone marrow. Conclusions: bFGF can stimulate osteogenesis and bone marrow adipogenesis concurrently at red marrow sites, but not at fatty marrow sites. In contrast, EP4A stimulates bone formation at skeletal sites with hematopoietic and fatty marrow and simultaneously decreased fatty marrow area and the number of adipocytes in the bone marrow, suggesting that osteogenesis occurs at the expense of adipogenesis.