Zhu Sheng, Häussling Victor, Aspera-Werz Romina H, Chen Tao, Braun Bianca, Weng Weidong, Histing Tina, Nussler Andreas K
Department of Trauma and Reconstructive Surgery, BG Trauma Center Tuebingen, Siegfried Weller Institute for Trauma Research, Eberhard Karls University Tuebingen, 72076 Tuebingen, Germany.
Int J Mol Sci. 2020 Dec 23;22(1):53. doi: 10.3390/ijms22010053.
Co-culture models have become mandatory for obtaining better insights into bone homeostasis, which relies on the balance between osteoblasts and osteoclasts. Cigarette smoking (CS) has been proven to increase the risk of osteoporosis; however, there is currently no proven treatment for osteoporosis in smokers excluding cessation. Bisphosphonates (BPs) are classical anti-osteoclastic drugs that are commonly used in examining the suitability of bone co-culture systems in vitro as well as to verify the response to osteoporotic stimuli. In the present study, we tested the effects of BPs on cigarette smoke extract (CSE)-affected cells in the co-culture of osteoblasts and osteoclasts. Our results showed that BPs were able to reduce CSE-induced osteoporotic alterations in the co-culture of osteoblasts and osteoclasts such as decreased matrix remodeling, enhanced osteoclast activation, and an up-regulated receptor activator of nuclear factor (NF)-kB-ligand (RANKL)/osteoprotegerin (OPG) ratio. In summary, BPs may be an effective alternative therapy for reversing osteoporotic alterations in smokers, and the potential mechanism is through modulation of the RANKL/OPG ratio.
共培养模型已成为深入了解骨稳态的必要手段，骨稳态依赖于成骨细胞和破骨细胞之间的平衡。吸烟已被证明会增加患骨质疏松症的风险；然而，目前除了戒烟外，尚无已证实的针对吸烟者骨质疏松症的治疗方法。双膦酸盐（BPs）是经典的抗破骨细胞药物，常用于体外研究骨共培养系统的适用性以及验证对骨质疏松刺激的反应。在本研究中，我们测试了双膦酸盐对成骨细胞和破骨细胞共培养中受香烟烟雾提取物（CSE）影响的细胞的作用。我们的结果表明，双膦酸盐能够减少成骨细胞和破骨细胞共培养中CSE诱导的骨质疏松改变，如基质重塑减少、破骨细胞活化增强以及核因子（NF）-κB配体（RANKL）/骨保护素（OPG）比值上调。总之，双膦酸盐可能是逆转吸烟者骨质疏松改变的一种有效替代疗法，其潜在机制是通过调节RANKL/OPG比值。
