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Glucose‐dependent regulation of osteoclast H + ‐ATPase expression: Potential role of p38 MAP‐kinase
Author(s) -
Larsen Kirsten I.,
Falany Marina L.,
Ponomareva Larissa V.,
Wang Wei,
Williams John P.
Publication year - 2002
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.10252
Subject(s) - osteoclast , p38 mitogen activated protein kinases , bone resorption , kinase , mitogen activated protein kinase , glucose transporter , endocrinology , medicine , chemistry , glucose uptake , snf3 , protein kinase a , biology , microbiology and biotechnology , biochemistry , in vitro , insulin
Abstract Bone resorption is glucose concentration dependent. Mechanisms regulating glucose‐dependent increases in bone resorption have not been identified. Glucose activates p38 MAP‐kinase in other cells and since MAP kinases activate transcription factors, we hypothesized that glucose‐stimulated bone resorption may be modulated by increased expression of the vacuolar H + ‐ATPase. Glucose activates osteoclast p38 MAP‐kinase in a time and concentration‐dependent manner as determined by Western analysis with phospho‐specific p38 antibody while total p38 levels are unchanged. The K 0.5 for glucose‐dependent activation of p38 MAP‐kinase is ∼7 mM, activation is maximal at 30 min and is elevated but returning to basal levels by 60 min. The concentration‐dependent increase in H + ‐ATPase expression was confirmed by Northern analysis. The specific inhibitor of p38 MAP‐kinase, SB203580, inhibited glucose transport in osteoclasts, as well as glucose concentration‐dependent increases in bone resorption and expression of H + ‐ATPase A and B subunits. Glucose had no effect on calmodulin expression levels that are regulated in response to other environmental changes. The glucose‐stimulated increase in H + ‐ATPase mRNA expression is a specific response to glucose since glucose has little effect on G3PDH mRNA levels. We conclude that glucose regulates osteoclast H + ‐ATPase expression by a mechanism likely to involve p38 MAP‐kinase. J. Cell. Biochem. 87: 75–84, 2002. © 2002 Wiley‐Liss, Inc.