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Advanced Glycation End Products (AGEs), but not High Glucose, Inhibit the Osteoblastic Differentiation of Mouse Stromal ST2 Cells Through the Suppression of Osterix Expression, and Inhibit Cell Growth and Increasing Cell Apoptosis

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Abstract

Diabetes mellitus is known to be associated with osteoporotic fractures through a decrease in osteoblastic bone formation rather than an increase in osteoclastic bone resorption. However, its precise mechanism is unknown, and we examined whether or not high glucose or advanced glycation end products (AGEs), which play key roles in the pathogenesis and complications of diabetes, would affect the osteoblastic differentiation, growth, and apoptosis of mouse stromal ST2 cells. Ten to 200 μg/mL AGE2 or AGE3 alone dose-dependently inhibited the mineralization. AGE2 or AGE3 alone (200 μg/mL) significantly inhibited alkaline phosphatase (ALP) activities as well as the mineralization of the cells (p < 0.01). In contrast, 22 mM glucose alone or in combination with 200 μg/mL AGE2 or AGE3 did not affect these cellular phenotypes. Real-time PCR showed that AGE2 or AGE3 alone (200 μg/mL) significantly decreased mRNA expressions of osteocalcin as well as osterix on day 14 (p < 0.01). Western blot analysis showed that AGE2 or AGE3 alone (200 μg/mL) also decreased the levels of Runx2 and osterix protein expressions on days 7 and 14. AGE2 or AGE3 significantly suppressed cell growth and increased apoptotic cell death in time- and dose-dependent manners (p < 0.01). Moreover, AGE3 alone (200 μg/mL) significantly increased mRNA expression of the receptor for AGEs (RAGE) on days 2 and 3 (p < 0.01). These results suggest that AGE2 and AGE3, but not high glucose, may inhibit the osteoblastic differentiation of stromal cells by decreasing osterix expression and partly by increasing RAGE expression, as well as inhibiting cell growth and increasing cell apoptosis.

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Authors and Affiliations

  1. Department of Internal Medicine 1, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan

    Kyoko Okazaki, Toru Yamaguchi, Ken-ichiro Tanaka, Masakazu Notsu, Noriko Ogawa, Shozo Yano & Toshitsugu Sugimoto

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  1. Kyoko Okazaki
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  2. Toru Yamaguchi
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  3. Ken-ichiro Tanaka
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  7. Toshitsugu Sugimoto
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Correspondence to Toru Yamaguchi.

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Okazaki, K., Yamaguchi, T., Tanaka, Ki. et al. Advanced Glycation End Products (AGEs), but not High Glucose, Inhibit the Osteoblastic Differentiation of Mouse Stromal ST2 Cells Through the Suppression of Osterix Expression, and Inhibit Cell Growth and Increasing Cell Apoptosis. Calcif Tissue Int 91, 286–296 (2012). https://doi.org/10.1007/s00223-012-9641-2

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  • DOI: https://doi.org/10.1007/s00223-012-9641-2

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