Platelet-derived growth factor BB enhances osteoclast formation and osteoclast precursor cell chemotaxis
Platelet-derived growth factor BB enhances osteoclast formation and osteoclast precursor cell chemotaxis
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血小板衍生生长因子 BB 增强破骨细胞形成和破骨细胞前体细胞趋化性
DOI：
10.1007/s00774-016-0773-8
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发表时间：
2017-07-01
影响因子：
3.3
通讯作者：
Li, Zu-bing
中科院分区：
文献类型：
--
作者：
Li, Dian-qi;Wan, Qi-long;Li, Zu-bing
破骨细胞形成增强会增加骨吸收，从而触发骨重塑。血小板衍生生长因子BB(PDGF-BB)可促进前体细胞归巢、血管生成和骨愈合，因此也可治疗骨质疏松症。然而，PDGF-BB对破骨细胞形成的影响还不完全清楚。我们研究了外源重组PDGF-BB是否直接影响破骨细胞的形成和破骨细胞前体细胞的趋化。将小鼠单核巨噬细胞系RAW264.7和骨髓源性巨噬细胞与重组小鼠血小板衍生生长因子受体β抑制剂(AG-1295)或Janus激酶2抑制剂(AG-490)共同培养，分析其对体外破骨细胞生成的影响。对16周龄SD大鼠(n=18)下颌骨骨折处局部应用PDGF-BB加或不加AG-490或AG-1295 1~2周，分析其对体内破骨细胞生成的影响。分析不同处理对破骨细胞形成、破骨细胞前体细胞迁移和破骨细胞信号分子表达的影响。PDGF-BB在体外和体内均能促进破骨细胞的形成，而AG-490和AG-1295则抑制这一作用。PDGF-BB促进RAW264.7细胞中细胞外信号调节蛋白1/2(ERK1/2)、Akt和信号转导与转录激活因子3(STAT3)的磷酸化。AG-490可抑制PDGF-BB诱导的STAT3磷酸化。PDGF-BB促进RAW264.7细胞迁移和破骨细胞信号分子(即活化T细胞核因子1、树突状细胞表达的7跨膜蛋白和B细胞淋巴瘤2)的基因表达，而AG-1295、AG-490或S3I-201(STAT3抑制剂)治疗减弱了这一作用。PDGF-BB促进破骨细胞的形成，促进破骨细胞前体细胞的趋化，促进STAT3、Akt和ERK1/2的磷酸化，而AG-1295和AG-490则抑制这一作用。这些发现反映了PDGF-BB在骨生物学中的复杂性。
Enhanced osteoclast formation increases bone resorption, which triggers bone remodeling. Platelet-derived growth factor BB (PDGF-BB) enhances precursor cell homing, angiogenesis, and bone healing, and thereby could also treat osteoporosis. However, the effect of PDGF-BB on osteoclast formation is not fully understood. We investigated whether exogenous recombinant PDGF-BB directly affects osteoclast formation and osteoclast precursor cell chemotaxis. The murine monocyte–macrophage cell line RAW264.7 and bone-marrow-derived macrophages were cultured with recombinant mouse PDGF-BB with or without a platelet-derived growth factor receptor β inhibitor (AG-1295) or a Janus kinase 2 inhibitor (AG-490) to analyze the effect on osteoclastogenesis in vitro. PDGF-BB with or without AG-490 or AG-1295 was locally administrated in the mandibular fracture of 16-week-old Sprague Dawley rats (n= 18) for 1–2 weeks to analyze the effect on osteoclastogenesis in vivo. The effect of the treatments on osteoclast formation, osteoclast precursor cell migration, and expression of osteoclastogenic signaling molecules was analyzed. PDGF-BB enhanced osteoclast formation both in vitro and in vivo, but AG-490 and AG-1295 inhibited this effect. PDGF-BB enhanced phosphorylation of extracellular-signal-regulated kinase 1/2 (ERK1/2), Akt, and signal transducer and activator of transcription 3 (STAT3) in RAW264.7 cells. AG-490 inhibited PDGF-BB-induced STAT3 phosphorylation. PDGF-BB enhanced RAW264.7 cell migration and gene expression of osteoclastogenic signaling molecules (i.e., nuclear factor of activated T cells 1, dendrocyte-expressed seven transmembrane protein, and B-cell lymphoma 2), and treatment with AG-1295, AG-490, or S3I-201 (a STAT3 inhibitor) reduced this effect. PDGF-BB enhanced osteoclast formation, osteoclast precursor cell chemotaxis, and phosphorylation of STAT3, Akt, and ERK1/2. but AG-1295 and AG-490 reduced this effect. These findings reflect the complexity of PDGF-BB in bone biology.