Ginsenoside Rb2가 C2C12 세포의 뼈모세포분화에 미치는 영향
The effects of ginsenoside Rb2 on osteoblastic differentiation of C2C12 cells
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골다공증은 뼈 형성에 비해 뼈 흡수가 증가하여 골량이 감소하는 대사성 질환이다. 현재 골다공증 치료약물로는 주로 뼈파괴세포의 뼈흡수를 억제하는 약물을 사용하고 있으나 여러 유해 작용으로 그 사용이 제한되고 있어 기존 치료법에 비해 위험이 적은 신규 뼈형성 촉진약물 개발이 필요하다. 인삼은 가장 흔히 사용되는 한약제 중 하나로 여러 질환에 치료 효과가 있으며 골다공증에도 치료 효과가 있는 것으로 알려져있다. 인삼의 주요 활성 성분인 ginsenoside 중 차지하는 비율이 높으며 항골다공증 효과가 보고되고 있는ginsenoside Rb1 (G-Rb1)과 Rb2 (G-Rb2)가 뼈형성에 미치는 영향을 밝히기 위하여 환경에 따라 근육세포, 지방세포, 뼈모세포로 분화할 수 있어 분화 전단계의 전구세포로 알려져있는 C2C12 세포를 이용하여 세포증식와 뼈모세포 분화 유전자 발현에 관하여 연구하였다. G-Rb1과 G-Rb2는 C2C12 세포의 증식을 유의하게 증가시켰다. 또한, G-Rb2는 C2C12 세포에서 뼈모세포 분화의 주요 조절자인 runt-related transcription factor-2 (Runx2)의 mRNA 발현을 유의하게 증가시켜 뼈모세포 분화를 촉진할 수 있음을보여주었다. G-Rb2는 C2C12세포에서 에스트로겐 수용체 α와 β의 mRNA 발현을 상승시켰다. 특히G-Rb2에 의하여 에스트로겐 수용체 β의 발현이 에스트로겐 수용체 α보다 더 큰 폭으로 증가하였다. 위의 결과는 G-Rb2가 뼈모세포 전구세포의 증식을 증가시키고 뼈모세포의 분화를 촉진할 수 있어 뼈형성 촉진기전을 가진 새로운 골다공증 치료약물의 후보물질이 될 수 있음을 보여준다.
Abstract
There is a strong need to develop novel anabolic agents for the treatment of osteoporosis that present fewer risks in comparison to conventional therapy. Panax ginseng is a common and well-recognized herbal medicine. Its biological activities have mostly been attributed to its principal components, namely, the ginsenosides. Our study focused on examining the effects of ginsenoside Rb1 (G-Rb1) and Rb2 (G-Rb2) on the proliferation of C2C12 cells, multipotent mesenchymal progenitor cells, as well as their osteogenic differentiation. G-Rb1 and G-Rb2 significantly increased C2C12 cell proliferation. G-Rb2 exhibited a significant increase in the mRNA expression of runt-related transcription factor-2 (Runx2), a key regulator of osteogenesis after 24 hours of culture in osteogenic media, indicating its potential in promoting osteogenic differentiation. Moreover, G-Rb2 upregulated the mRNA expression of both estrogen receptor α and β. Notably, G-Rb2 exhibited a stronger upregulation of estrogen receptor β expression compared to estrogen receptor α. The observed results suggest that G-Rb2 has the potential to promote the osteogenic differentiation of osteoblasts. Furthermore, the upregulation of estrogen receptors α and β by G-Rb2 suggests that it may have a bone-protective effect.
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