Li Xudong, Cui Quanjun, Kao Chinghai, Wang Gwo Jaw, Balian Gary
Department of Orthopaedic Surgery, University of Virginia, School of Medicine, Charlottesville, VA 22908, USA.
Bone. 2003 Oct;33(4):652-9. doi: 10.1016/s8756-3282(03)00239-4.
The mechanism whereby lovastatin can counteract steroid-induced osteonecrosis and osteoporosis is poorly understood. We assessed the effect of lovastatin on a multipotential cell line, D1, which is capable of differentiating into either the osteoblast or the adipocyte lineage. The expression of bone cell and fat cell transcription factors Cbfa1/Runx2 and PPARgamma2, respectively, were determined. 422aP2 gene expression was analyzed. Osteocalcin promoter activity was measured by cotransfecting the cells with the phOC-luc and pSV beta-Gal plasmids. Lovastatin enhanced osteoblast differentiation as assessed by a 1.8x increase in expression of Cbfa1/Runx2 and by a 5x increase in osteocalcin promoter activity. Expression of PPARgamma2 was decreased by 60%. By enhancing osteoblast gene expression and by inhibiting adipogenesis, lovastatin may shunt uncommitted osteoprogenitor cells in marrow from the adipocytic to the osteoblastic differentiation pathway. Future evaluation of lovastatin and other lipid-lowering drugs will help determine their potential as therapeutic agents for osteonecrosis and osteoporosis.
洛伐他汀能够对抗类固醇诱导的骨坏死和骨质疏松症的机制目前还知之甚少。我们评估了洛伐他汀对一种多能细胞系D1的作用，该细胞系能够分化为成骨细胞或脂肪细胞谱系。分别测定了骨细胞和脂肪细胞转录因子Cbfa1/Runx2和PPARgamma2的表达。分析了422aP2基因的表达。通过将细胞与phOC-luc和pSVβ-Gal质粒共转染来测量骨钙素启动子活性。通过Cbfa1/Runx2表达增加1.8倍以及骨钙素启动子活性增加5倍来评估，洛伐他汀增强了成骨细胞分化。PPARgamma2的表达降低了60%。通过增强成骨细胞基因表达和抑制脂肪生成，洛伐他汀可能会使骨髓中未定向的骨祖细胞从脂肪细胞分化途径转向成骨细胞分化途径。未来对洛伐他汀和其他降脂药物的评估将有助于确定它们作为骨坏死和骨质疏松症治疗药物的潜力。
