Hypoxia induces BMP-2 expression via ILK, Akt, mTOR, and HIF-1 pathways in osteoblasts

Wen-Pei Tseng, Shu Ning Yang, Chih Ho Lai, Chih Hsin Tang

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

It has been shown that hypoxia stimulation regulates bone formation, maintenance, and repair. Bone morphogenetic protein (BMP) plays important roles in osteoblastic differentiation and bone formation. However, the effects of hypoxia exposure on BMP-2 expression in cultured osteoblasts are largely unknown. Here we found that hypoxia stimulation increasedmRNAand protein levels of BMP-2 by qPCR, Western blot and ELISA assay in osteoblastic cells MG-63, hFOB and bone marrow stromal cells M2-10B4. Integrin-linked kinase (ILK) inhibitor (KP-392), Akt inhibitor (1L-6-hydroxymethyl-chiro-inositol-2-[(R)-2-O-methyl-3- O-octadecylcarbonate]) or mammalian target of rapamycin (mTOR) inhibitor (rapamycin) inhibited the potentiating action of hypoxia. Exposure to hypoxia increased the kinase activity of ILK and phosphorylation of Akt and mTOR. Furthermore, hypoxia also increased the stability and activity of HIF-1 protein. The binding of HIF-1α to the HRE elements after exposure to hypoxia was measured by EMSA assay. Moreover, the use of pharmacological inhibitors or genetic inhibition revealed that both ILK/Akt and mTOR signaling pathway were potentially required for hypoxia-induced HIF-1a activation and subsequent BMP-2 up-regulation. Taken together, our results provide evidence that hypoxia enhances BMP-2 expression in osteoblasts by an HIF-1a-dependent mechanism involving the activation of ILK/Akt and mTOR pathways.

Original languageEnglish
Pages (from-to)810-818
Number of pages9
JournalJournal of Cellular Physiology
Volume223
Issue number3
DOIs
Publication statusPublished - 2010 Jun 1

Fingerprint

Bone Morphogenetic Protein 2
Osteoblasts
Sirolimus
Bone
1L-6-hydroxymethyl-chiro-inositol 2(R)-2-O-methyl-3-O-octadecylcarbonate
Assays
Chemical activation
Bone Morphogenetic Proteins
Phosphorylation
Osteogenesis
Proteins
Repair
Phosphotransferases
integrin-linked kinase
Hypoxia
Mesenchymal Stromal Cells
Up-Regulation
Western Blotting
Enzyme-Linked Immunosorbent Assay
Maintenance

All Science Journal Classification (ASJC) codes

  • Cell Biology
  • Clinical Biochemistry
  • Physiology

Cite this

Tseng, Wen-Pei ; Yang, Shu Ning ; Lai, Chih Ho ; Tang, Chih Hsin. / Hypoxia induces BMP-2 expression via ILK, Akt, mTOR, and HIF-1 pathways in osteoblasts. In: Journal of Cellular Physiology. 2010 ; Vol. 223, No. 3. pp. 810-818.
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Hypoxia induces BMP-2 expression via ILK, Akt, mTOR, and HIF-1 pathways in osteoblasts. / Tseng, Wen-Pei; Yang, Shu Ning; Lai, Chih Ho; Tang, Chih Hsin.

In: Journal of Cellular Physiology, Vol. 223, No. 3, 01.06.2010, p. 810-818.

Research output: Contribution to journalArticle

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