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Activation of the PI 3 K / A kt pathway by oxidative stress mediates high glucose‐induced increase of adipogenic differentiation in primary rat osteoblasts
Author(s) -
Zhang Yu,
Yang JianHong
Publication year - 2013
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.24607
Subject(s) - runx2 , adipogenesis , oxidative stress , pi3k/akt/mtor pathway , endocrinology , medicine , protein kinase b , chemistry , osteoblast , reactive oxygen species , microbiology and biotechnology , signal transduction , biology , biochemistry , adipose tissue , in vitro
Diabetes mellitus is associated with increased risk of osteopenia and bone fracture that may be related to hyperglycemia. However, the mechanisms accounting for diabetic bone disorder are unclear. Here, we showed that high glucose significantly promoted the production of reactive oxygen species (ROS) in rat primary osteoblasts. Most importantly, we reported for the first time that ROS induced by high glucose increased alkaline phosphatase activity, inhibited type I collagen (collagen I) protein level and cell mineralization, as well as gene expression of osteogenic markers including runt‐related transcription factor 2 (Runx2), collagen I, and osteocalcin, but promoted lipid droplet formation and gene expression of adipogenic markers including peroxisome proliferator‐activated receptor gamma, adipocyte fatty acid binding protein (aP2), and adipsin, which were restored by pretreatment with N‐acetyl‐ L ‐cysteine (NAC), a ROS scavenger. Moreover, high glucose‐induced oxidative stress activated PI3K/Akt pathway to inhibited osteogenic differentiation but stimulated adipogenic differentiation. In contrast, NAC and a PI3K inhibitor, LY‐294002, reversed the down‐regulation of osteogenic markers and the up‐regulation of adipogenic markers as well as the activation of Akt under high glucose. These results indicated that oxidative stress played a key role in high glucose‐induced increase of adipogenic differentiation, which contributed to the inhibition of osteogenic differentiation. This process was mediated by PI3K/Akt pathway in rat primary osteoblasts. Hence, suppression of oxidative stress could be a potential therapeutic approach for diabetic osteopenia. J. Cell. Biochem. 114: 2595–2602, 2013. © 2013 Wiley Periodicals, Inc.