ILIZAROV CALLUS DISTRACTION PRODUCES SYSTEMIC BONE CELL MITOGENS

ILIZAROV CALLUS DISTRACTION PRODUCES SYSTEMIC BONE CELL MITOGENS
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DOI:
10.1002/jor.1100130420
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发表时间:
1995-07-01
影响因子:
2.8
通讯作者:
CLAES, L
CLAES, L
中科院分区:
医学3区
文献类型:
--
作者:
HOLBEIN, O;NEIDLINGERWILKE, C;CLAES, L

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我们验证了这样一种假设,即在骨痂牵张过程中施加应变可诱导全身成骨细胞刺激因子,从而增强局部和全身成骨细胞的活性。为了研究骨痂牵张过程中菌株诱导的成骨细胞刺激因子的全体性发生,我们研究了12例骨痂牵张患者的血清在成骨细胞系SaOS-2上的有丝分裂能力(第一部分)。6例接受刚性胫骨高位截骨术(即无牵引)的患者的血清样本作为对照。检测血清中血小板源性生长因子和转化生长因子。在第二部分的研究中,通过对同一患者皮质骨外植体分离的成骨细胞进行循环刺激,在简化模型中研究了机械应变的体外效应;一种专门研制的装置用于细胞拉伸。揭骨后第3 ~ 4周血清中SaOS-2细胞的增殖显著增加(p < 0.005)。相比之下,截骨患者的血清不能诱导或降低SaOS-2细胞的有丝分裂能力。骨痂牵张组和截骨组血清中血小板衍生生长因子浓度均显著升高(p < 0.01)。而牵张组(刺激SaOS-2细胞增殖的血清)血清中转化生长因子- β水平升高(p < 0.05),而截骨组血清中转化生长因子- β水平未升高。体外循环拉伸可刺激成骨细胞增殖(p < 0.05),显著增加转化生长因子- β的生成(p < 0.05)。这些发现表明,机械刺激的成骨细胞有可能增加增殖,并产生额外的丝裂原,以响应循环应变。该研究支持了机械刺激组织诱导系统因子增强成骨细胞活性从而影响愈伤组织形成的观点。这些因素的分离和表征可能会导致血清测定来预测骨痂牵拉期间的成骨。
We tested the hypothesis that the application of strain during callus distraction induces systemic osteoblast stimulating factors that enhance osteoblast activity both locally and systemically. To study the systemic occurrence of strain-induced osteoblast stimulating factor during callus distraction, we investigated the mitogenic capacity of sera from 12 patients who had undergone callus distraction on the osteoblastic cell line SaOS-2 (part I). Serum samples from six patients who had undergone rigidly fixed high tibial osteotomy (i.e., without distraction) served as controls. The sera were assayed for platelet-derived growth factor and transforming growth factor-beta. In part II of the study, the in vitro effects of mechanical strain were investigated in a simplified model by cyclic stimulation of osteoblast cultures isolated from cortical bone explants from the same patients; a specially developed apparatus was used for cell-stretching. Sera taken during the third to fourth week of callus distraction demonstrated a significant increase in proliferation of SaOS-2 cells (p < 0.005). In contrast, sera from patients who had had an osteotomy failed to induce or decreased the mitogenic capacity of SaOS-2 cells. The concentration of platelet-derived growth factor increased significantly (p < 0.01) in sera from both the patients who had undergone callus distraction and the controls who had had osteotomy. However, the level of transforming growth factor-beta was increased (p < 0.05) in the sera from the patients who had distraction (sera that stimulated proliferation of SaOS-2 cells), but the level was not increased in the sera from patients who had osteotomy. Cyclic stretching of osteoblasts in vitro stimulated proliferation (p < 0.05) and increased the cellular production of transforming growth factor-beta significantly (p < 0.05). These findings suggest that mechanically stimulated osteoblasts have the potential to increase proliferation and to produce additional mitogens in response to cyclic strain. This study supports the notion that mechanically stimulated tissue induces systemic factors that enhance osteoblast activity and thus influence the formation of callus. Isolation and characterization of these factors potentially could lead to serum assays to predict osteogenesis during callus distraction.