The effects of mechanically loaded osteocytes and inflammation on bone remodeling in a bisphosphonate-induced environment
The effects of mechanically loaded osteocytes and inflammation on bone remodeling in a bisphosphonate-induced environment
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DOI：
10.1016/j.bone.2019.07.008
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发表时间：
2019-10-01
期刊：
影响因子：
4.1
通讯作者：
Saunders, Marnie M.
中科院分区：
文献类型：
--
作者：
George, Estee L.;Truesdell, Sharon L.;Saunders, Marnie M.
双膦酸盐相关的颌骨坏死是因转移性癌症和骨质疏松症接受双膦酸盐治疗的患者拔牙后出现的一种疾病。这种情况的复杂性需要多细胞模型来解决两个关键危险因素的净效应：机械创伤（病理超负荷）和炎症。在这项工作中，由聚二甲基硅氧烷芯片和机械加载装置组成的系统用于将双膦酸盐处理的骨细胞暴露于机械创伤。具体来说，用有效的含氮双膦酸盐唑来膦酸处理骨细胞，并通过基质拉伸暴露于短期病理超负荷。在骨重建过程中，骨细胞凋亡在将前破骨细胞吸引到损伤部位方面发挥着重要作用。因此，乳酸脱氢酶活性、细胞死亡和蛋白质表达被评估为负荷的函数。此外，还量化了骨细胞可溶性因子对破骨细胞和成骨细胞功能活性的影响。在存在或不存在炎症成分、脂多糖和干扰素γ的情况下对破骨细胞活性和骨吸收进行量化。结果表明，与细菌感染相关的炎症可能会阻碍破骨细胞的骨吸收。此外，骨细胞可能通过改变作用于成骨细胞的可溶性信号的表达来响应过载，从而减弱骨形成。这些发现深入了解了与双膦酸盐相关的颌骨坏死所涉及的多细胞相互作用。
Bisphosphonate-related osteonecrosis of the jaw is a disease appearing after tooth removal in patients undergoing bisphosphonate treatment for metastasizing cancers and osteoporosis. The complexity of the condition requires a multicellular model to address the net effects of two key risk factors: mechanical trauma (pathologic overload) and inflammation. In this work, a system comprised of a polydimethylsiloxane chip and mechanical loading device is used to expose bisphosphonate-treated osteocytes to mechanical trauma. Specifically, osteocytes are treated with the potent nitrogen-containing bisphosphonate, zoledronic acid, and exposed to short-term pathologic overload via substrate stretch. During bone remodeling, osteocyte apoptosis plays a role in attracting pre-osteoclasts to sites of damage; as such, lactate dehydrogenase activity, cell death and protein expression are evaluated as functions of load. Additionally, the effects of osteocyte soluble factors on osteoclast and osteoblast functional activity are quantified. Osteoclast activity and bone resorption are quantified in the presence and absence of inflammatory components, lipopolysaccharide and interferon gamma. Results suggest that inflammation associated with bacterial infection may hinder bone resorption by osteoclasts. In addition, osteocytes may respond to overload by altering expression of soluble signals that act on osteoblasts to attenuate bone formation. These findings give insight into the multicellular interactions implicated in bisphosphonate-related osteonecrosis of the jaw.