Department of Oral and Maxillofacial Surgery, University medical centre of Johannes Gutenberg University Mainz, Augustusplatz 2, 55131 Mainz, Germany.
Head Face Med. 2011 Feb 7;7(1):4. doi: 10.1186/1746-160X-7-4.
Bisphosphonates are therapeutics of bone diseases, such as Paget's disease, multiple myeloma or osteoclastic metastases. As a severe side effect the bisphosphonate induced osteonecrosis of the jaw (BONJ) often requires surgical treatment and is accompanied with a disturbed wound healing.Therefore, the influence on adhesion and migration of human osteoblasts (hOB) after bisphosphonate therapy has been investigated by morphologic as well as gene expression methods.
By a scratch wound experiment, which measures the reduction of defined cell layer gap, the morphology and migration ability of hOB was evaluated. A test group of hOB, which was stimulated by zoledronate 5 × 10(-5)M, and a control group of unstimulated hOB were applied. Furthermore the gene expression of integrin aVb3 and tenascin C was quantified by Real-Time rtPCR at 5 data points over an experimental period of 14 days. The bisphosphonates zoledronate, ibandronate and clodronate have been compared with an unstimulated hOB control.
After initially identical migration and adhesion characteristics, zoledronate inhibited hOB migration after 50 h of stimulation. The integrinavb3 and tenascin C gene expression was effected by bisphosphonates in a cell line dependent manner with decreased, respectively inconsistent gene expression levels over time. The non-nitrogen containing bisphosphonates clodronate led to decreased gene expression levels.
Bisphosphonates seem to inhibit hOB adhesion and migration. The integrin aVb3 and tenascin C gene expression seem to be dependent on the cell line. BONJ could be enhanced by an inhibition of osteoblast adhesion and migration. The gene expression results, however, suggest a cell line dependent effect of bisphosphonates, which could explain the interindividual differences of BONJ incidences.
双膦酸盐是治疗骨骼疾病的药物，如 Pagets 病、多发性骨髓瘤或破骨细胞转移。作为一种严重的副作用，双膦酸盐引起的颌骨骨坏死（BONJ）通常需要手术治疗，并伴有伤口愈合障碍。因此，通过形态学和基因表达方法研究了双膦酸盐治疗后对人成骨细胞（hOB）黏附和迁移的影响。
通过划痕实验测量定义的细胞层间隙的减少，评估 hOB 的形态和迁移能力。将 hOB 用唑来膦酸 5×10(-5)M 刺激作为实验组，未刺激的 hOB 作为对照组。此外，在 14 天的实验期间，通过实时 rtPCR 在 5 个数据点定量测量整合素 aVb3 和 tenascin C 的基因表达。将唑来膦酸、伊班膦酸和氯膦酸与未刺激的 hOB 对照组进行比较。
在最初具有相同的迁移和黏附特性后，唑来膦酸在刺激 50 小时后抑制 hOB 迁移。整合素 avb3 和 tenascin C 的基因表达在细胞系依赖性方式中受到双膦酸盐的影响，随时间推移基因表达水平降低或不一致。不含氮的双膦酸盐氯膦酸导致基因表达水平降低。
双膦酸盐似乎抑制 hOB 黏附和迁移。整合素 aVb3 和 tenascin C 的基因表达似乎依赖于细胞系。BONJ 可通过抑制成骨细胞黏附和迁移而加重。然而，基因表达结果表明双膦酸盐存在细胞系依赖性作用，这可以解释 BONJ 发生率的个体差异。
