綠茶兒茶素對OSM誘導人類成骨細胞製造cyr61的調控機制

Abstract

Cyr61為近幾年新發現的蛋白質，一般咸認它與細胞增生、遷移、附著、細胞存活與分化、細胞間質生成、血管新生及腫瘤生成有關。然而它在骨細胞所扮演的確切角色及機制目前仍不十分清楚。在我們的實驗中，發現osteoblast（成骨細胞）在OSM處理的情況下，會導致cyr61的生成。在cyr61表現途徑中，經由實驗發現OSM是經由轉錄 (transcription) 過程中的調控，亦即經由mRNA level產生調控作用，而這其中的過程可能是經由Akt及MAPK pathway而來：在Akt的途徑中，應是經由OSM誘導p-Akt生成，進而活化p-IkB，最後經由NF-kB之p65 subunit進到核中進行轉譯上的調控作用，而活化了cyr61的表現；另外，在MAPK的途徑中，應是經由p-38及JNK的影響。我們同時研究是否有藥物可有效抑制這樣的反應，發現加入EGCG可有效抑制成骨細胞中由OSM所誘導的cyr61之生成，且此抑制作用亦是經由抑制Akt、IkB及NF-kB而達成。

Cyr61 is a novel protein which is found in recent years, it is well known as the function with cell proliferation, migration, adhesion, formation of extracellular matrix (ECM), angiogenesis and tumorigenesis. However, the role of cyr61 and the regulation mechanism are still unclear now. In our study, we found that treat osteoblast cells with OSM will up-regulates the expression of cyr61. The results of our experiments reveal that OSM-stimulated cyr61 expression is regulated at transcriptional level, which means mRNA level, but not regulated at post-translational level. Cyr61 expression may be regulated by Akt and Mitogen-activated protein kinase (MAPK) pathway. We determined that OSM induces cyr61 expression by phosphorylation and activation of Akt (p-Akt) and IkB (p-IkB). Thereafter, activated form of IkB leads to the activation of Nuclear factor-kB (NF-kB) which translocates into the nucleus to regulates gene expression at tran-scriptional level and enhances cyr61 protein expression. Also, in our study, the expression of cyr61 may be regulated by p38 and JNK. In this study, we also found that in osteoblast cells, EGCG effectively inhibit the activation of Akt, IkB, NF-kB and the expression of cyr61 which are stimulated by OSM.