RGD Reference Report - Non-virus-mediated transfer of siRNAs against Runx2 and Smad4 inhibit heterotopic ossification in rats. - Rat Genome Database

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Non-virus-mediated transfer of siRNAs against Runx2 and Smad4 inhibit heterotopic ossification in rats.

Authors: Xue, T  Mao, Z  Lin, L  Hou, Y  Wei, X  Fu, X  Zhang, J  Yu, C 
Citation: Xue T, etal., Gene Ther. 2010 Mar;17(3):370-9. doi: 10.1038/gt.2009.154. Epub 2009 Nov 26.
RGD ID: 12880052
Pubmed: PMID:19940863   (View Abstract at PubMed)
DOI: DOI:10.1038/gt.2009.154   (Journal Full-text)

Heterotopic ossification of muscles, tendons and ligaments are a common problem affecting patient with trauma or received elective surgery. But the existing preventive or therapeutic methods all have disadvantages. Runt-related protein 2 (Runx2) and Smad4 are two regulators that have important roles in the differentiation of osteoblast. In this study, we attempted to examine the effect of Runx2 and Smad4 on the development of heterotopic ossification in vitro. We constructed non-virus-containing small interference RNAs (siRNAs) against Runx2 and Smad4 and tested it with reverse transcriptase-PCR and western blot. We then analyzed the independent effect of Runx2- and Smad4-specific siRNAs and their cooperative effect on the formation of heterotopic ossification induced by trauma in rats. The effects were measured with computed tomography scanning, hematoxylin and eosin staining and immunohistochemistry. We found that the Runx2- and Smad4-specific siRNAs inhibited the expression of Runx2 and Smad4 at the level of messenger RNA and protein. Runx2 and Smad4 independently inhibited the formation of heterotopic ossification. Moreover, their co-expression significantly enhanced the inhibition of heterotopic ossification compared with the independent effect. We suggest that gene therapy to inhibit Runx2 and Smad4 by RNAi could be a powerful approach to prevent or treat heterotopic ossification.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Runx2Ratosteoblast differentiation  IMP  RGD 
Smad4Ratosteoblast differentiation  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Runx2  (RUNX family transcription factor 2)
Smad4  (SMAD family member 4)

Genes (Mus musculus)
Runx2  (runt related transcription factor 2)
Smad4  (SMAD family member 4)

Genes (Homo sapiens)
RUNX2  (RUNX family transcription factor 2)
SMAD4  (SMAD family member 4)


Additional Information