成骨細胞數目是造成骨質疏鬆症的重要因素之一。黑升麻活性成分之ㄧ，cimicifugin為三萜類衍生物，本研究發現cimicifugin對於成骨細胞具有分化作用。使用cimicifugin處理MG 63細胞，cimicifugin無法促進成骨細胞的增生作用，但會促進成骨細胞轉錄因子Runx2的轉錄作用。
Cimicifugin可促進成骨細胞成熟的早期分化指標(鹼性磷酸酶的活性ALP activity)與晚期分化指標(骨鈣素的含量osteocalcin levels以及礦化作用Minerlization )。Cimicifugin誘導成骨細胞的分化作用伴隨著JNK的磷酸化並具有增加雌激素受體-?Estrogen receptor-? 磷酸化的現象。接著，藉由Estrogen receptor-ㄖ磻蹌?ICI 182,780 可有效降低成骨細胞的早期與晚期分化指標(ALP activity與osteocalcin levels)，因此Estrogen receptor-ㄕbcimicifugin誘導成骨細胞分化作用中扮演著重要的角色。
此外，cimicifugin影響腫瘤壞死因子-?(TNF-? 誘導ㄧ氧化氮 (NO) 與IL-6(介白素-6)的產生，並抑制內生性前列腺素(PGE2)的含量，當cimicifugin處理MG 63細胞後，可減少TNF-˙冗冇O與IL-6的產生以及內生性PGE2。因此得知，cimicifugin可降低MG 63細胞中，由TNF-ㄘ瓟梇悸熊o炎性損傷(inflammatory damage)。在本篇研究中，我們證實了cimicifugin透過JNK及Estrogen receptor-ㄧ纁|誘導成骨細胞進行分化作用，或野戎i以成為治療骨質疏鬆症的新藥物。 The survival of osteoblast cells is one of the determinants of the development of osteoporosis in patients. This study is the first to investigate the osteoblast differentiation of cimicifugin, a triterpene derivative in a human osteoblast-like cell lines, MG 63. Cimicifugin did not exhibit significant effects on cell growth in MG 63 cells. In contrast, cimicifugin increased the marker of osteoblastic maturation (ALP activity) and differentiation (osteocalcin production). Cimicifugin also enhanced the transcript level of osteoblast-specific transcription factor Runx2. The effect of cimicifugin on the TNF-?induced production of nitric oxide (NO) in osteoblasts was examined. Treatment with cimicifugin decreased the TNF-?induced production of NO in osteoblasts. Induction of differentiation by cimicifugin was associated with increased JNK phosophorylation, and upregulation and phosphorylation of estrogen receptor. Blocking estrogen by antagonist (ICI 182,780) significantly decreased osteoblastic differentiation, suggesting estrogen receptor plays an important role in cimicifugin -induced cell differentiation. In addition, cimicifugin also decreased TNF-?mediated inflammatory in human osteoblast-like cell line. In this study, we demonstrate that cimicifugin induced osteoblastic differentiation through JNK and estrogen pathway, and it is a promising agent for treating osteoporosis.
