1. Intercellular Communication between Keratinocytes and Fibroblasts Induces Local Osteoclast Differentiation: a Mechanism Underlying Cholesteatoma-Induced Bone Destruction
- Author
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Saori Itoi-Ochi, Hidenori Inohara, Ichiro Katayama, Keizo Nishikawa, Masayuki Furuya, Masaru Ishii, Maki Uenaka, Ryusuke Imai, Yoriko Iwamoto, Josef M. Penninger, Yumi Ohta, and Tetsuo Morihana
- Subjects
Keratinocytes ,musculoskeletal diseases ,0301 basic medicine ,Cell signaling ,Cellular differentiation ,Osteoclasts ,Cell Communication ,Biology ,Bone resorption ,Mice ,03 medical and health sciences ,Osteoclast ,medicine ,Animals ,Cholesteatoma ,Molecular Biology ,Cells, Cultured ,RANK Ligand ,Cell Differentiation ,Articles ,Cell Biology ,Fibroblasts ,medicine.disease ,Coculture Techniques ,Epithelium ,Cell biology ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,RANKL ,Immunology ,biology.protein - Abstract
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 κB 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.
- Published
- 2016