Intercellular communication between keratinocytes and fibroblasts induces 1 local osteoclast differentiation: a mechanism underlying 2 cholesteatoma-induced bone destruction
Authors
Yoriko Iwamoto, Keizo Nishikawa, Ryusuke Imaia,, Masayuki Furuya, Maki Uenaka, Yumi Ohta, Tetsuo Morihana, Saori Itoi-Ochi, Josef M. Penninger, Ichiro Katayama, Hidenori Inohara and Masaru Ishii
Institution
Osaka
Country
Japan
Year
2016
Journal
Molecular and Cellular Biology
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, in 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 co-culture 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.