Inhibiting wear particles-induced osteolysis with doxycycline
Inhibiting wear particles-induced osteolysis with doxycycline
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DOI：
10.1111/j.1745-7254.2007.00638.x
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发表时间：
2007-10-01
影响因子：
8.2
通讯作者：
Ke-rong Dai
中科院分区：
文献类型：
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作者：
Chao Zhang;Ting-ting Tang;Ke-rong Dai
目的：研究多西环素（DOX）对破骨细胞生成、成熟破骨细胞命运和功能以及磨损颗粒引起的骨溶解的影响，为关节置换术后无菌性松动和骨溶解的治疗提供依据。方法：用NF-κB配体受体激活剂和巨噬细胞集落刺激因子从小鼠骨髓单核细胞中产生破骨细胞。将浓度分别为5、10、15和20μg/mL的DOX添加至培养基中。 7天后，通过抗酒石酸酸性磷酸酶（TRAP）染色测定破骨细胞。从新生兔中分离出成熟的破骨细胞，并在24孔板或骨片上培养3 d。将浓度分别为5、10、15和20μg/mL的DOX添加到培养基中。 TRAP染色后，对破骨细胞进行计数，对骨切片上的吸收进行定量，并在甲苯胺蓝和Mayer-苏木精染色后计算面积。将聚甲基丙烯酸甲酯（PMMA）或超高分子量聚乙烯（UHMWPE）颗粒植入C57BL/J6小鼠的颅骨上。 DOX剂量分别为2和10 mg.kg(-1).d(-1),腹腔注射7 d。 7天后，取出颅骨并进行病理分析。结果：DOX治疗有效抑制体外破骨细胞生成，影响成熟破骨细胞的命运，并抑制成熟破骨细胞，引起骨吸收。体内数据表明，DOX 强烈抑制 PMMA 或 UHMWPE 诱导的骨溶解和破骨细胞生成。结论：DOX能有效抑制破骨细胞生成，影响成熟破骨细胞的命运，抑制骨溶解和破骨细胞生成引起的磨损颗粒。 DOX 可能有助于治疗或预防磨损颗粒引起的骨溶解和无菌性松动，因为它对破骨细胞的生成以及成熟破骨细胞的命运和功能有影响。
Aim: To study the effect of doxycycline (DOX) on osteoclastogenesis, mature osteoclast fate and function, wear particles-induced osteoeolysis, and to provide some foundation for treating aseptic loosening and osteolysis after joint arthroplasty. Methods: Osteoclasts were generated from mouse bone marrow monocytes with the receptor activator of NF-kappa B ligand and the macrophage colony stimulating factor. DOX at a concentration of 5, 10, 15, and 20 mu g/mL was respectively added to the medium. Seven days later, the osteoclasts were determined through tartrate-resistant acid phosphatase (TRAP) staining. Mature osteoclasts were isolated from newborn rabbits and cultured for 3 d in 24-well plates or on bone slices. DOX at a concentration of 5, 10, 15, and 20 mu g/mL was respectively added to the medium. After TRAP staining, the osteoclasts were counted, resorption on bone slices was quantified, and the area was calculated after toluidine blue and Mayer-hematoxylin staining. Polymethyl methacrylate (PMMA) or ultra-high molecular weight polyethylene (UHMWPE) particles were implanted on the calvariae of C57BL/J6 mice. DOX, at a dose of 2 and 10 mg.kg(-1).d(-1), was respectively given intraperitoneally for 7 d. Seven days later, the calvariae were removed and processed for pathological analysis. Results: DOX treatment effectively inhibited in vitro osteoclastogenesis, affected the fate of mature osteoclasts, and inhibited mature osteoclasts, causing bone resorption. In vivo data indicated that DOX strongly inhibited PMMA or UHMWPE-induced osteolysis and osteoclastogenesis. Conclusion: DOX can effectively inhibit osteoclastogenesis and affect mature osteoclast fate and suppress wear particles induced by osteolysis and osteoclastogenesis. DOX might be useful in the treatment or prevention of wear particles-induced osteolysis and aseptic loosening for its effect on osteoclast generation and mature osteoclast fate and function.