論文 - 詳細
| RRC ID | 12444 |
|---|---|
| 著者 | Siddappa R, Mulder W, Steeghs I, van de Klundert C, Fernandes H, Liu J, Arends R, van Blitterswijk C, de Boer J. |
| タイトル | cAMP/PKA signaling inhibits osteogenic differentiation and bone formation in rodent models. |
| ジャーナル | Tissue Eng Part A |
| Abstract |
We previously demonstrated that cAMP-mediated protein kinase A (PKA) activation induces in vitro osteogenesis and in vivo bone formation by human mesenchymal stem cells (hMSCs). To analyze the species-specific response of this phenomenon and to translate our findings into a clinical trial, suitable animal models and cell lines are desirable. In this report, we assessed whether PKA plays a similar proosteogenic role played by two commonly used PKA activators-N6,2'-O-dibutyryl-cAMP (db-cAMP) and 8-bromo cAMP (8b-cAMP)-in a number of model systems. To this end, we treated MC3T3-E1 cells, mouse calvarial osteoblasts, mouse MSCs, and rat MSCs with cAMP. We demonstrate that cAMP inhibits osteogenesis in rodent cell types, evidenced by inhibition of osteogenic markers such as alkaline phosphatase (ALP), osteocalcin (BGLAP), and collagen type 1 (COL1A1). In support of this, ex vivo-cultured mouse calvaria exposed to db-cAMP showed a reduction in bone volume. Interestingly, cAMP even stimulated adipogenic differentiation in rat MSCs. Taken together, our data demonstrate that cAMP inhibits osteogenesis in vitro and bone formation ex vivo in rodent models in contrast to our earlier findings in hMSCs. The species discrepancy in response to various osteogenic signals is a critical need to be tested in clinically relevant models to translate the fundamental findings in lower species level to clinical applications. |
| 巻・号 | 15(8) |
| ページ | 2135-43 |
| 公開日 | 2009-8-1 |
| DOI | 10.1089/ten.tea.2008.0512 |
| PMID | 19231969 |
| MeSH | 8-Bromo Cyclic Adenosine Monophosphate / pharmacology Adipogenesis / drug effects Alkaline Phosphatase / antagonists & inhibitors Animals Brain / cytology Brain / drug effects Bucladesine / pharmacology Calcification, Physiologic / drug effects Cell Differentiation* / drug effects Cell Line Cyclic AMP / metabolism* Cyclic AMP-Dependent Protein Kinases / metabolism* Gene Expression Regulation / drug effects Mesenchymal Stem Cells / cytology Mesenchymal Stem Cells / drug effects Mesenchymal Stem Cells / metabolism Mice Models, Animal Osteogenesis* / drug effects Osteogenesis* / genetics Rats Signal Transduction* / drug effects |
| IF | 3.508 |
| 引用数 | 33 |
| WOS 分野 | BIOTECHNOLOGY & APPLIED MICROBIOLOGY CELL & TISSUE ENGINEERING CELL BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | MC3T3-E1(RCB1126) |