Hypoxia-induced MTA1 promotes MC3T3 osteoblast growth but suppresses MC3T3 osteoblast differentiation

Eur J Med Res. 2015 Feb 3;20(1):10. doi: 10.1186/s40001-015-0084-x.

Abstract

Background: Bone fracture is one of the most common physical injuries in which gene expression and the microenvironment are reprogramed to facilitate the recovery process.

Methods: By specific siRNA transfection and MTT assay, we evaluated the effects of metastasis-associated gene 1 (MTA1) in osteoblast growth. To show the role of MTA1 in osteoblast under hypoxia conditions, by overexpressing and silencing MTA1 expression, we performed mineral deposition and alkaline phosphatase activity assay to observe the differentiation status of osteoblast cells. Real-time PCR and Western blot assays were adopted to detect the expression of certain target genes.

Results: Here, we reported that hypoxia-induced MTA1 expression through hypoxia-induced factor 1 alpha (HIF-1α) and stimulated the growth of osteoblast MC3T3 cells. Silencing of MTA1 through specific siRNA suppressed MC3T3 cell growth and elicited cell differentiation and induced alkaline phosphatase activation and the upregulation of bone morphogenetic protein-2 and osteocalcin.

Conclusions: We found that MTA1 was regulated by HIF-1α in hypoxia circumstance to suppress osteoblast differentiation. These findings provide new insights for bone fracture healing and new strategies to develop potential targets to promote fracture healing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Cell Differentiation*
  • Cell Growth Processes
  • Cell Hypoxia
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Mice
  • Osteoblasts / cytology
  • Osteoblasts / metabolism*
  • Osteoblasts / physiology
  • Oxygen / metabolism*
  • Repressor Proteins
  • Trans-Activators
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Mta1 protein, mouse
  • Repressor Proteins
  • Trans-Activators
  • Transcription Factors
  • Oxygen