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 Bonewald, Byung Joon Kim

Research output: Contribution to journalArticle

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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 - 2013
Externally publishedYes

Fingerprint

Inbred OLETF Rats
Osteocytes
Bone Density
Minerals
Rats
Bone
Down-Regulation
Glucagon-Like Peptide 1
Osteocalcin
Thigh
Femur
Insulin
Glucose
Messenger RNA
Western Blotting
Confocal microscopy
Osteoblasts
Medical problems
exenatide
Parathyroid Hormone

Keywords

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

ASJC Scopus subject areas

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

Cite this

Exendin-4 increases bone mineral density in type 2 diabetic OLETF rats potentially through the down-regulation of SOST/sclerostin in osteocytes. / Kim, Ju Young; Lee, Seong Kyu; Jo, Kyung Jin; Song, Dae Yong; Lim, Dong Mee; Park, Keun Young; Bonewald, Lynda; Kim, Byung Joon.

In: Life Sciences, Vol. 92, No. 10, 2013, p. 533-540.

Research output: Contribution to journalArticle

Kim, Ju Young ; Lee, Seong Kyu ; Jo, Kyung Jin ; Song, Dae Yong ; Lim, Dong Mee ; Park, Keun Young ; Bonewald, Lynda ; Kim, Byung Joon. / Exendin-4 increases bone mineral density in type 2 diabetic OLETF rats potentially through the down-regulation of SOST/sclerostin in osteocytes. In: Life Sciences. 2013 ; Vol. 92, No. 10. pp. 533-540.
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T1 - Exendin-4 increases bone mineral density in type 2 diabetic OLETF rats potentially through the down-regulation of SOST/sclerostin in osteocytes

AU - Kim, Ju Young

AU - Lee, Seong Kyu

AU - Jo, Kyung Jin

AU - Song, Dae Yong

AU - Lim, Dong Mee

AU - Park, Keun Young

AU - Bonewald, Lynda

AU - Kim, Byung Joon

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

KW - Bone mineral density

KW - Exendin-4

KW - Glucagon-like peptide-1 receptor

KW - Osteocytes

KW - Sclerostin

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