Intercellular Communication between Keratinocytes and Fibroblasts Induces Local Osteoclast Differentiation: a Mechanism Underlying Cholesteatoma-Induced Bone Destruction
Intercellular Communication between Keratinocytes and Fibroblasts Induces Local Osteoclast Differentiation: a Mechanism Underlying Cholesteatoma-Induced Bone Destruction
复制标题
DOI：
10.1128/mcb.01028-15
复制
发表时间：
2016-06-01
影响因子：
5.3
通讯作者：
Ishii, Masaru
中科院分区：
文献类型：
--
作者：
Iwamoto, Yoriko;Nishikawa, Keizo;Ishii, Masaru
骨稳态通过骨吸收破骨细胞和骨形成成骨细胞之间的活性平衡来维持。骨吸收平衡的改变导致溶骨性骨病，如类风湿性关节炎和牙周炎。破骨细胞分化受核因子κ B配体受体激活因子（RANKL）调节，在某些病理条件下，RANKL由T和B淋巴细胞和滑膜细胞产生。然而，在其他疾病中骨破坏的机制却知之甚少。中耳乳突瘤是中耳的一种表皮囊肿，由角化鳞状上皮过度增殖引起，可导致致命的并发症。在这项研究中，我们成功地建立了一个模型，为中耳炎，表皮囊肿样组织，这有可能诱导破骨细胞在小鼠。此外，使用由角质形成细胞、成纤维细胞和破骨细胞前体组成的体外共培养系统来证明角质形成细胞通过诱导成纤维细胞中的RANKL来刺激破骨细胞分化。因此，本研究表明，角质形成细胞和成纤维细胞之间的细胞间通讯参与破骨细胞的分化和功能，这可能提供一个新的治疗策略的分子基础，为中耳炎诱导的骨破坏。
Bone homeostasis is maintained by a balance in activity between bone-resorbing osteoclasts and bone-forming osteoblasts. Shifting the balance toward bone resorption causes osteolytic bone diseases such as rheumatoid arthritis and periodontitis. Osteoclast differentiation is regulated by receptor activator of nuclear factor kappa B ligand (RANKL), which, under some pathological conditions, is produced by T and B lymphocytes and synoviocytes. However, the mechanism underlying bone destruction in other diseases is little understood. Bone destruction caused by cholesteatoma, an epidermal cyst in the middle ear resulting from hyperproliferation of keratinizing squamous epithelium, can lead to lethal complications. In this study, we succeeded in generating a model for cholesteatoma, epidermal cyst-like tissue, which has the potential for inducing osteoclastogenesis in mice. Furthermore, an in vitro coculture system composed of keratinocytes, fibroblasts, and osteoclast precursors was used to demonstrate that keratinocytes stimulate osteoclast differentiation through the induction of RANKL in fibroblasts. Thus, this study demonstrates that intercellular communication between keratinocytes and fibroblasts is involved in the differentiation and function of osteoclasts, which may provide the molecular basis of a new therapeutic strategy for cholesteatoma-induced bone destruction.