Greiner S, Kadow-Romacker A, Schmidmaier G, Wildemann B
Center for Musculoskeletal Surgery, Julius Wolff Institut, Berlin Brandenburg Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, D-13353 Berlin, Germany.
J Biomed Mater Res A. 2009 Oct;91(1):288-95. doi: 10.1002/jbm.a.32245.
The antiresorptive activity of bisphosphonates such as zoledronic acid (ZOL) has been shown in vitro to be because of their effect on osteoclasts and osteoblasts. However, whether the effect of ZOL on monocultures might be reproducible on cocultures and whether cell interactions might influence this effect has not been described. The aim of the study was to investigate the effect of ZOL on cocultures of osteoblasts and osteoclasts in vitro. ZOL was incorporated in an implant coating based on poly(D,L-lactide) in different concentrations (10-50 microM). Cell number was measured, and procollagen I synthesis, osteoprotegerin (OPG) secretion and soluble receptor activator of nuclear factor-kappaB ligand (sRANKL) were analyzed. Moreover, TRAP-positive cells and resorption lacunas on dentin chips were counted. Results showed that cell viability was not affected when treated with doses equivalent up to 50-microM ZOL-coated implants (ZOL-CI). Procollagen I and OPG synthesis was highest when treated with 10 microM ZOL-CI, whereas sRANKL showed no significant decrease when treated with the investigated concentrations of ZOL-CI. TRAP-positive cells were decreased when treated with ZOL-CI in a dose-dependent manner. Resorption activity of osteoclasts was not significantly decreased when treated with investigated concentrations of ZOL-CI. Exposure to specific concentrations of ZOL-CI showed a beneficial effect on osteoblast differentiation and protein synthesis. Formation of osteoclast was decreased, whereas a significant decrease in sRANKL secretion and resorption activity of osteoclasts could not be shown. The investigated effect on cocultures might be clinically useful to support fracture healing and to reduce orthopedic implant loosening.
唑来膦酸（ZOL）等双膦酸盐的抗吸收活性在体外已被证明是由于它们对破骨细胞和成骨细胞的作用。然而，ZOL对单一培养物的作用在共培养物中是否可重现，以及细胞间相互作用是否会影响这种作用，尚未见报道。本研究的目的是在体外研究ZOL对成骨细胞和破骨细胞共培养物的影响。将ZOL以不同浓度（10 - 50微摩尔）掺入基于聚（D，L-丙交酯）的植入物涂层中。测量细胞数量，并分析I型前胶原合成、骨保护素（OPG）分泌和核因子-κB配体可溶性受体激活剂（sRANKL）。此外，对牙本质片上的抗酒石酸酸性磷酸酶（TRAP）阳性细胞和吸收陷窝进行计数。结果显示，用高达50微摩尔ZOL涂层植入物（ZOL-CI）等效剂量处理时，细胞活力不受影响。用10微摩尔ZOL-CI处理时，I型前胶原和OPG合成最高，而用所研究浓度的ZOL-CI处理时，sRANKL未显示出显著降低。用ZOL-CI处理时，TRAP阳性细胞呈剂量依赖性减少。用所研究浓度的ZOL-CI处理时，破骨细胞的吸收活性未显著降低。暴露于特定浓度的ZOL-CI对成骨细胞分化和蛋白质合成显示出有益作用。破骨细胞形成减少，但sRANKL分泌和破骨细胞吸收活性未显示出显著降低。所研究的对共培养物的作用在临床上可能有助于促进骨折愈合和减少骨科植入物松动。
