Tingart Markus, Beckmann Johannes, Opolka Alfred, Matsuura Maiko, Wiech Oliver, Grifka Joachim, Grässel Susanne
Department of Orthopedic Surgery, University of Regensburg, Kaiser-Karl V-Allee 3, 93077 Bad Abbach, Germany.
Calcif Tissue Int. 2008 Apr;82(4):300-8. doi: 10.1007/s00223-008-9111-z. Epub 2008 Mar 5.
Osteonecrosis of the femoral head (ONFH) usually affects young individuals and has a major impact on lifestyle. Notably, the pathogenetic mechanisms of osteonecrosis are unresolved and no effective treatment exists. The objective of this study was to assess the gene expression levels of factors regulating bone formation and remodeling (bone morphogenetic protein [BMP]-2, BMP-7, Runx2, osteocalcin, osteoprotegerin [OPG]) in patients with ONFH and to compare them to those of patients with primary osteoarthritis (OA). The cellular and macromolecular composition of the bone matrix was assessed by osteocalcin immunohistochemistry, and the three-dimensional organization of trabecular bone was characterized by micro-computed tomographic analysis. Our results demonstrate that gene expression of BMP-2, BMP-7, and Runx2 is elevated in patients with ONFH. We observed increased extracellular osteocalcin deposition, presumably caused by a higher number of osteoblasts in concordance with increased activity of Runx2. Constant gene expression level of OPG implies an unchanged osteoclast differentiation rate in ONFH bone. We found no significant change in bone volume, connectivity, and structural model index; further, no significant differences were detected for trabecular properties in ONFH bone. In conclusion, we have shown increased gene expression of factors regulating bone formation and remodeling in the femoral head and/or neck of patients with ONFH. Further, we observed an increase in osteocalcin immunoreactivity and osteoblast/osteocyte cell number, while no significant changes in trabecular microarchitecture were detected. This study increases our understanding of the pathophysiology and repair process following ONFH and might help in the development of new treatment strategies in the future.
股骨头坏死（ONFH）通常影响年轻人，对生活方式有重大影响。值得注意的是，骨坏死的发病机制尚未明确，且不存在有效的治疗方法。本研究的目的是评估股骨头坏死患者中调节骨形成和重塑的因子（骨形态发生蛋白[BMP]-2、BMP-7、Runx2、骨钙素、骨保护素[OPG]）的基因表达水平，并将其与原发性骨关节炎（OA）患者的基因表达水平进行比较。通过骨钙素免疫组织化学评估骨基质的细胞和大分子组成，并通过显微计算机断层扫描分析表征小梁骨的三维结构。我们的结果表明，股骨头坏死患者中BMP-2、BMP-7和Runx2的基因表达升高。我们观察到细胞外骨钙素沉积增加，推测这是由于成骨细胞数量增加以及Runx2活性增加所致。OPG的基因表达水平恒定意味着股骨头坏死骨中破骨细胞分化率不变。我们发现骨体积、连通性和结构模型指数没有显著变化；此外，在股骨头坏死骨的小梁特性方面未检测到显著差异。总之，我们已经表明，股骨头坏死患者股骨头和/或颈部中调节骨形成和重塑的因子的基因表达增加。此外，我们观察到骨钙素免疫反应性和成骨细胞/骨细胞数量增加，而小梁微结构未检测到显著变化。这项研究增进了我们对股骨头坏死病理生理学和修复过程的理解，并可能有助于未来开发新的治疗策略。
