Exendin-4 increases bone mineral density in type 2 diabetic OLETF rats potentially through the down-regulation of SOST/sclerostin in osteocytes

Ju Young Kim, Seong Kyu Lee, Kyung Jin Jo, Dae Yong Song, Dong Mee Lim, Keun Young Park, Lynda F. Bonewald, Byung Joon Kim

Research output: Contribution to journalArticle

72 Scopus citations

Abstract

Aim Glucagon-like peptide-1 (GLP-1) receptor participates in the control of bone resorption in GLP-1 knockout mice. Also, GLP-1 induces an insulin- and parathyroid hormone-independent osteogenic action through osteoclasts and osteoblasts in insulin-resistant and type 2 diabetic rats. Osteocytes are now considered central to bone homeostasis. A secreted product of osteocytes, sclerostin, inhibits bone formation. However, the effect of GLP-1 on osteocytes remains unclear. Therefore, we investigated the effect of GLP-1 on bone mineral density (BMD), and the cellular and molecular mechanisms associated with osteocytes. Main methods We investigated the presence of GLP-1 receptors in osteocyte-like MLO-Y4 cells and osteocytes of rat femurs through RT-PCR, Western blot and confocal microscopy, and investigated the effect of exendin-4 on the expression of mRNA (by quantitative real-time RT-PCR) and protein (by Western blot) of SOST/sclerostin in osteocyte-like MLO-Y4 cells during culture under normal or high-glucose (30 mM) conditions, and measured circulating levels of sclerostin, osteocalcin, and tartrate-resistant alkaline phosphatase (TRAP) 5b and femoral BMD in type 2 diabetic OLETF rats treated with exendin-4. Key findings GLP-1 receptor was present on MLO-Y4 cells and osteocytes of rat femurs. Exendin-4 reduced the mRNA expression and protein production of SOST/sclerostin under normal or high-glucose conditions in MLO-Y4 cells. Exendin-4 reduced serum levels of sclerostin, increased serum levels of osteocalcin, and increased femoral BMD in type 2 diabetic OLETF rats. Significance These findings suggest that exendin-4 might increase BMD by decreasing the expression of SOST/sclerostin in osteocytes in type 2 diabetes.

Original languageEnglish (US)
Pages (from-to)533-540
Number of pages8
JournalLife Sciences
Volume92
Issue number10
DOIs
StatePublished - Feb 18 2013
Externally publishedYes

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Keywords

  • Bone mineral density
  • Exendin-4
  • Glucagon-like peptide-1 receptor
  • Osteocytes
  • Sclerostin

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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