Osteocytes up-regulate the terminal differentiation of pre-osteoblasts via gap junctions

Yoichi Nishikawa, Yuko Akiyama, Kiyofumi Yamamoto, Masayuki Kobayashi, Eri Watanabe, Nobukazu Watanabe, Noriyoshi Shimizu, Yoshikazu Mikami, Kazuo Komiyama

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12 Citations (Scopus)


We examined cell-to-cell interaction between pre-osteoblasts and osteocytes using MC3T3-E1 and MLO-Y4, respectively. First, GFP expressing MC3T3-E1 (E1-GFP) cells were generated to isolate the cells from co-culture with MLO-Y4. No changes were observed in the expression of osteogenic transcription factors Runx2, Osterix, Dlx5 and Msx2, but expression of alkaline phosphatase (ALP) and bone sialoprotein (BSP) in E1-GFP co-cultured with MLO-Y4 was 300-400-fold greater than that in mono-cultured E1-GFP. In addition, mineralized nodule formation was drastically increased in co-cultured E1-GFP cells compared to mono-cultured cells. Patch clamp assay showed the presence of gap junctions between E1-GFP and MLO-Y4. Furthermore, when the gap junction inhibitor carbenoxolone (CBX) was added to the culture, increased expression of ALP and BSP in E1-GFP co-cultured with MLO-Y4 was suppressed. These results suggest that gap junction detected between pre-osteoblasts and osteocytes plays an important role on the terminal differentiation of pre-osteoblasts.

Original languageEnglish
Pages (from-to)1-6
Number of pages6
JournalBiochemical and Biophysical Research Communications
Issue number1
Publication statusPublished - 2 Jan 2015


  • Alkaline phosphatase
  • Bone sialoprotein
  • Gap junction
  • Osteoblasts
  • Osteocytes


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