摘要或動機

細胞脂肪分化是造成肥胖、骨質疏鬆、和糖尿病的重要前置因素。我們若要維持良好身材又想省去減肥藥的問題，那麼我們必須了解造成脂肪化的原因，才可能擁有好的預防之道。利用人類骨髓間質細胞可以分化成骨質與脂肪等細胞的特性，我們研究氧化壓力對間質細胞\r
Ras基因轉換表現後骨質與脂肪分化的影響。結果發現以添加超氧根 (O₂^-，l5nM)形成氧化壓力，可促進正常Ras基因表現的間質細胞朝骨質分化;相反地，超氧根會促進\r
Ras基因突變而不表現的細胞，朝向脂肪分化的現象。進一步研究其作可原理，發現氧化壓力可促進 RaS蛋白質啟動細胞外訊息活化酵素(ERK)，接著驅動骨質轉錄因子(CBFA1)表現，再到骨鈣蛋白質與骨結節形成。而抗氧化酵素(超氧根轉化酵素;SOD,5OOU/ml)的作用，可以抑制正常Ras基因細胞氧化壓力下骨質分化的進行;但不能防止氧化壓力促進Ras基因突變細胞，朝向脂肪分化的作用。總結而言:Ras基因的表現與否，是決定脂肪分化的關鍵切換點;也是影響氧化壓力對間質細胞朝骨質分化的樞紐。這種基因與氧化壓力互動影響骨質與脂肪分化的剖析，將有助於提醒人們:使用抗氧化劑來調節抗衰老、肥胖、和美容時，必須是在不同情況和不同基因體質的人，有所不同。
\r
Human\r
mesenchymal stem cells are able to differentiate into bone, muscle, cartilage or\r
fat tissues. Our preliminary study with human mesenchymal cell line (HS-5) showed\r
that HS-5 cells could differentiate to bone, cartilage and muscle but not fat cells\r
as determined by histochemical staining of phenotypes. We have further studied the\r
influence of oxidative stress on the switch between bone and fat cell differentiation.\r
Results showed that oxidative stress started with exogenous superoxide, produced\r
by the interaction of xanthine oxidase and hypoxanthine, promoted the differentiation\r
of osteogenic lineage showing expression of osteocalcin and bone nodule formations.\r
The mechanism was investigated and superoxide was found to induce ERK (extracellular\r
regulated signal kinase) activation; and then the expression of osteogenic specific\r
transcriptional factor (CBFA1). A plasmid containing ras-mutant (Ser 17 Asn) which\r
can inactivate the expression of ERK was transfected into the HS-5 cells for studying\r
the influence of oxidative stress on ras-mutated mesenchymal cells. Surprisingly,\r
it was found that oxidative stress did not promote osteogenesis but it enhanced\r
adipogenesis from the ras-mutated HS-5 cells. Further studies indicated that superoxide\r
neither induced ERK activation nor CBFA1 expression, but it did enhance expression\r
of adipogenic specific transcriptional factor (C/EBPα) and lipoprotein lipase in\r
the ras-mutated mesenchvmal cells. Taken together, the study model to induce the\r
bone cell differentiation from human mesenchymal stem cells may be employed to make\r
bone cells for tissue engineering.