The small molecule PKA-specific cyclic AMP analogue as an inducer of osteoblast-like cells differentiation and mineralization.
The small molecule PKA-specific cyclic AMP analogue as an inducer of osteoblast-like cells differentiation and mineralization.
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DOI：
10.1002/term.395
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发表时间：
2012-01
影响因子：
3.3
通讯作者：
Laurencin, Cato T.
中科院分区：
文献类型：
--
作者：
Lo, Kevin W. -H.;Kan, Ho Man;Ashe, Keshia M.;Laurencin, Cato T.
关键词：
成骨细胞分化是骨形成、骨修复和骨再生的重要标志，但成骨细胞分化是一个非常复杂的过程，受不同的信号机制控制。几个研究小组已经报道，环磷酸腺苷（cAMP）信号系统负责调节成骨细胞分化。尽管如此，迄今为止，cAMP分子在这一过程中的主要作用仍然存在争议。此外，控制成骨细胞分化的潜在cAMP依赖性信号级联尚未阐明。在这份报告中，我们研究了cAMP依赖性蛋白激酶A（PKA）信号传导在成骨样MC 3 T3-E1细胞增殖、分化和矿化中的作用，使用PKA特异性小分子cAMP类似物6-Bnz-cAMP，浓度为100 µM。碱性磷酸酶（ALP）活性、Runx 2、骨桥蛋白（OPN）和骨钙素（OCN）蛋白表达作为成骨细胞特异性标志物，用于证明成骨细胞分化。此外，细胞外基质的钙测量被用作基质矿化或钙化的标志。我们在这里报告，PKA的小分子6-Bnz-cAMP的激活诱导成骨细胞分化和成骨样MC 3 T3-E1细胞的基质矿化。此外，如我们的细胞增殖研究所揭示的，6-Bnz-cAMP不诱导细胞毒性。因此，基于这些发现，我们提出PKA特异性小分子6-Bnz-cAMP可能作为一种新的骨诱导生长因子，用于骨再生工程中的骨组织修复和再生。
Osteoblastic differentiation is an important landmark for bone formation, bone repair and regeneration, however it is a very complex process controlled by different signaling mechanisms. Several groups have reported that the cyclic adenosine monophosphate (cAMP) signaling system is responsible for regulating osteoblast cell differentiation. Nonetheless, to date, the principle role of the cAMP molecules related to this process remains controversial. Moreover, the underlying cAMP-dependent signaling cascade governing the osteoblastic differentiation has not been clarified. In this report, we investigated the roles of the cAMP-dependent protein kinase A (PKA) signaling in proliferation, differentiation and mineralization of osteoblast-like MC3T3-E1 cells using the PKA-specific small molecule cAMP analogue, 6-Bnz-cAMP, at 100 µM. Alkaline phosphatase (ALP) activity, runt transcription factor 2 (Runx2), osteopontin (OPN) and osteocalcin (OCN) protein expressions were used as osteoblast-specific markers to demonstrate osteoblastic differentiation. Further, calcium measurement of the extracellular matrix was employed as the hallmark of matrix mineralization or calcification. We report here that activation of PKA by the small molecule 6-Bnz-cAMP induces osteoblastic differentiation and matrix mineralization of osteoblast-like MC3T3-E1 cells. Moreover, 6-Bnz-cAMP does not induce cytotoxicity to the cells as revealed by our cell proliferation studies. Therefore, based on these findings, we propose that the PKA-specific small molecule 6-Bnz-cAMP may serve as a novel bone-inducing growth factor for repairing and regenerating bone tissues during bone regenerative engineering.
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影响因子：
3.5
作者：
Cheung, WMW;Ng, WW;Kung, AWC
通讯作者：
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影响因子：
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作者：
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DOI：
10.1152/ajpcell.1997.272.6.c2005
发表时间：
1997-06-01
影响因子：
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通讯作者：
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影响因子：
64.5
作者：
Ducy, P;Zhang, R;Karsenty, G
通讯作者：
Karsenty, G
DOI：
10.1016/j.bbrc.2007.02.057
发表时间：
2007-04-20
影响因子：
3.1
作者：
Chen, Tain-Hsiung;Chen, Wei-Ming;Hung, Shih-Chieh
通讯作者：
Hung, Shih-Chieh