Gap junctional intercellular communication attenuates osteoclastogenesis induced by activated osteoblasts

Risa Kawatsura; Yusuke Hara; Masako Akiyama; Noriko Tachikawa; Ken-Ichi Nakahama

doi:10.1016/j.bbrc.2022.01.118

Gap junctional intercellular communication attenuates osteoclastogenesis induced by activated osteoblasts

Biochem Biophys Res Commun. 2022 Mar 15:597:71-76. doi: 10.1016/j.bbrc.2022.01.118. Epub 2022 Jan 31.

Authors

Risa Kawatsura¹, Yusuke Hara², Masako Akiyama³, Noriko Tachikawa⁴, Ken-Ichi Nakahama⁵

Affiliations

¹ Department of Cellular Physiological Chemistry, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan; Regenerative and Reconstructive Oral Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, Japan.
² Department of Cellular Physiological Chemistry, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
³ Research Administration Division, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
⁴ Regenerative and Reconstructive Oral Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, Japan.
⁵ Department of Cellular Physiological Chemistry, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan. Electronic address: nakacell@tmd.ac.jp.

PMID: 35124462
DOI: 10.1016/j.bbrc.2022.01.118

Abstract

Osteoblasts participate in both bone formation through the synthesis of extracellular matrix and osteoclast differentiation through the expression of osteoclast differentiation factor. Osteoblasts communicate with each other via gap junctions (GJ), which enable small molecules, such as cAMP, to move to adjacent cells. Therefore, we focused on the role of cAMP propagation between osteoblasts via GJ in the osteoclast-supporting activity of osteoblasts. Osteoclast-supporting activity was evaluated by a co-culture system of osteoblasts with bone marrow-derived mononuclear cells. In this system, ablation of Gja1, a gene encoding connexin 43, in osteoblasts promoted osteoclastogenesis induced by prostaglandin E₂ (PGE₂). A phosphodiesterase 4 inhibitor increased both osteoclastogenesis and the intracellular cAMP concentration ([cAMP]_i) in osteoblasts. Individual cell analysis of [cAMP]_i in osteoblasts revealed different responses of each osteoblast to PGE₂. Moreover, measurement of real-time [cAMP]_i demonstrated cAMP movement from cell to cell via GJ. The inhibition of GJ resulted in the upregulation of [cAMP]_i in osteoblasts stimulated by PGE2. This study suggested that GJ intercellular communication exerts protective effects against excess osteoclastogenesis via cAMP movement between osteoblasts.

Keywords: Connexin 43; Cyclic AMP; Gap junction; Osteoblast; Osteoclast.