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Hypergravity Stimulates Osteoblast Phenotype Expression: A Therapeutic Hint for Disuse Bone Atrophy
Author(s) -
MORITA SADAO,
NAKAMURA HIROSHI,
KUMEI YASUHIRO,
SHIMOKAWA HITOYATA,
OHYA KEIICHI,
SHINOMIYA KENICHI
Publication year - 2004
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1329.020
Subject(s) - osteocalcin , hypergravity , osteoblast , runx2 , endocrinology , medicine , chemistry , alkaline phosphatase , gene expression , biology , gene , in vitro , biochemistry , enzyme
A bstract : Physiological actions of osteoblasts are disordered by gravity unloading. We investigated the possibility that the appropriate level of hypergravity could improve osteoblast functions that are susceptible to mechanical unloading. We evaluated hypergravity effects on the 1α,25‐dihydroxyvitamin D 3 (VD)‐inducible osteocalcin expression of primary rat osteoblasts. Cell culture plates were centrifuged for 24 h at 3, 6, 12, 24, and 48 g in a 37°C incubator. The mRNA levels were analyzed by quantitative RT‐PCR. The mRNA levels for osteocalcin and vitamin D receptor (VD‐R) at 12 g were enhanced to 187% and 228% of the 1 g control, respectively. However, the excess hypergravity conversely decreased osteocalcin expression. Osteocalcin gene expression was enhanced by VD/VD‐R through the vitamin D‐responsive element in the promoter. The increased osteocalcin expression might reflect the augmented VD‐R expression. Alternatively, Runx2, a master gene of osteoblast differentiation, might be responsible for the osteocalcin induction, since the Runx2 mRNA levels were also increased to 247% of control at 12 g . Another VD‐inducible osteoblast phenotype, alkaline phosphatase, was also upregulated at 12 g and 24 g . The appropriate level of hypergravity enhanced the VD‐inducible expression of osteocalcin, a typical phenotype of osteoblast differentiation. These data suggest molecular features to prevent disuse bone atrophy of long‐term bed‐rest patients.