Parathyroid hormone-activated volume-sensitive calcium influx pathways in mechanically loaded osteocytes

Akimitsu Miyauchi, Kohei Notoya, Yuko Mikuni-Takagaki, Yasuyuki Takagi, Masayuki Goto, Yoshiki Miki, Teruko Takano-Yamamoto, Kenji Jinnai, Keiichi Takahashi, Masayoshi Kumegawa, Kazuo Chihara, Takuo Fujita

研究成果: Article査読

92 被引用数 (Scopus)


This paper documents for the first time a volume-sensitive Ca2+ influx pathway in osteocytes, which transmits loading-induced signals into bone formation. Stretch loading by swelling rat and chicken osteocytes in hypo- osmotic solution induced a rapid and progressive increase of cytosolic calcium concentration, [Ca2+](i). The influx of extracellular Ca2+ explains the increased [Ca2+](i) that paralleled the increase in the mean cell volume. Gadolinium chloride (Gd3+), an inhibitor of stretch- activated cation channels, blocked the [Ca2+](i) increase caused by hypotonic solutions. Also, the expression of α1C subunit of voltage-operated L-type Ca2+ channels (α1C) is required for the hypotonicity-induced [Ca2+](i) increase judging from the effect of α1C antisense oligodeoxynucleotides. Parathyroid hormone (PTH) specifically potentiated the hypotonicity-induced [Ca2+](i) increase in a dose-dependent manner through the activation of adenyl cyclase. The increases induced by both PTH and hypotonicity were observed primarily in the processes of the osteocytes. In cyclically stretched osteocytes on flexible-bottomed plates, PTH also synergistically elevated the insulin-like growth factor-1 mRNA level. Furthermore, Gd3+ and α1C antisense significantly inhibited the stretch-induced insulin-like growth factor-1 mRNA elevation. The volume-sensitive calcium influx pathways of osteocytes represent a mechanism by which PTH potentiates mechanical responsiveness, an important aspect of bone formation.

ジャーナルJournal of Biological Chemistry
出版ステータスPublished - 2000 2月 4

ASJC Scopus subject areas

  • 生化学
  • 分子生物学
  • 細胞生物学


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