University of Ljubljana, Department of Clinical Biochemistry, Ljubljana, Slovenia.
Arch Med Res. 2011 Jul;42(5):392-7. doi: 10.1016/j.arcmed.2011.08.005. Epub 2011 Aug 18.
New data show that increased adipogenesis in bone marrow may decrease osteoblastogenesis, resulting in osteoporosis (OP). Runt-related transcription factor 2 (RUNX2) and peroxisome proliferator-activated receptor γ (PPARγ) are two main transcriptional regulators controlling osteoblastogenesis and adipogenesis from the same precursor cell in bone-the mesenchymal stem cell. Because osteoarthritis (OA) and OP present the opposing bone phenotype, our aim was to determine whether the expression of selected adipogenic genes is lower in OA compared to OP bone tissue.
Bone samples were obtained from gender-matched OP (n = 54) and OA (n = 49) patients undergoing hip arthroplasty. Osteoblastogenesis and adipogenesis were estimated by gene expression analysis of RUNX2, PPARγ2 and their downstream genes.
In OA bone, significantly higher expression of PPARγ2 and adiponectin as well as RUNX2, osterix and osteocalcin were obtained, suggesting higher adipogenesis and osteoblastogenesis in OA than in OP. There were no differences in RUNX2/PPARγ2 and osteocalcin/adiponectin ratios between groups, suggesting similar balance of both processes. Higher perilipin 2, angiopoietin-like 4 and fatty-acid binding protein 4 mRNA levels in OP suggest activation of other transcription factors or hypoxic conditions in OP bone.
Regulation of bone formation by RUNX2 and PPARγ2 is modified in OA compared to OP, resulting in higher osteoblastogenesis and adipogenesis in OA. Both processes are similarly balanced in OP and OA but less active in OP.
新数据表明,骨髓中脂肪生成的增加可能会减少成骨细胞的生成,从而导致骨质疏松症(OP)。 runt 相关转录因子 2(RUNX2)和过氧化物酶体增殖物激活受体γ(PPARγ)是两种主要的转录调节因子,它们控制着骨骼中的前体细胞——间充质干细胞向成骨细胞和脂肪细胞分化。由于骨关节炎(OA)和 OP 呈现出相反的骨骼表型,我们的目的是确定与 OP 骨组织相比,OA 骨组织中选定的脂肪生成基因的表达是否较低。
从接受髋关节置换术的性别匹配的 OP(n=54)和 OA(n=49)患者中获得骨样本。通过 RUNX2、PPARγ2 及其下游基因的表达分析来评估成骨细胞和脂肪生成。
在 OA 骨中,获得了 PPARγ2 和脂联素以及 RUNX2、osterix 和骨钙素的表达明显更高,表明 OA 中的脂肪生成和成骨细胞生成高于 OP。两组之间 RUNX2/PPARγ2 和骨钙素/脂联素的比值没有差异,表明这两个过程的平衡相似。OP 中 perilipin 2、血管生成素样 4 和脂肪酸结合蛋白 4 mRNA 水平较高,提示 OP 骨中存在其他转录因子的激活或缺氧条件。
与 OP 相比,RUNX2 和 PPARγ2 对骨形成的调节在 OA 中发生了改变,导致 OA 中更高的成骨细胞生成和脂肪生成。这两个过程在 OP 和 OA 中平衡相似,但在 OP 中活性较低。