RGD Reference Report - Identification of CITED2 as a negative regulator of fracture healing. - Rat Genome Database

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Identification of CITED2 as a negative regulator of fracture healing.

Authors: Lee, JY  Taub, PJ  Wang, L  Clark, A  Zhu, LL  Maharam, ER  Leong, DJ  Ramcharan, M  Li, Z  Liu, Z  Ma, YZ  Sun, L  Zaidi, M  Majeska, RJ  Sun, HB 
Citation: Lee JY, etal., Biochem Biophys Res Commun. 2009 Oct 2;387(4):641-5. Epub 2009 Jul 14.
RGD ID: 5147852
Pubmed: PMID:19607804   (View Abstract at PubMed)
PMCID: PMC3008352   (View Article at PubMed Central)
DOI: DOI:10.1016/j.bbrc.2009.07.029   (Journal Full-text)

The transcription regulator CITED2 (CBP/p300-Interacting-Transactivator-with-ED-rich-tail-2) is known to suppress genes mediating angiogenesis and extracellular matrix (ECM) remodeling. However, it is unclear whether CITED2 has a role in controlling skeletal repair or remodeling. We tested the hypothesis that CITED2 functions in bone fracture healing by suppressing the expression of genes critical to ECM remodeling, angiogenesis and osteogenesis, importantly the matrix metalloproteinases (MMPs). Three hours following mandibular osteotomy or sham surgery of adult rats, osteotomy fronts were harvested and the expression of CITED2 and genes associated with fracture healing was ascertained by quantitative PCR. In parallel, gain-of-function studies examined the effect of overexpressing CITED2 on the expression and activity of several MMPs. In the fractured mandible, CITED2 expression was inversely related to the expression of MMP-2, -3, -9, -13, VEGF, HIF-1alpha, M-CSF, RANK-L, and OPG. Consistent with this, the over-expression of CITED2 in osteoblasts inhibited the expression and activity of MMP-2, -3, -9, and -13. Taken together, the studies suggest that CITED2 is a critical upstream regulator of fracture healing. The suppression of CITED2 early after fracture may allow an optimal initiation of the healing response.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CITED2HumanMandibular Fractures  ISOCited2 (Rattus norvegicus)mRNA:decreased expression:boneRGD 
Cited2RatMandibular Fractures  IEP mRNA:decreased expression:boneRGD 
Cited2MouseMandibular Fractures  ISOCited2 (Rattus norvegicus)mRNA:decreased expression:boneRGD 

Objects Annotated

Genes (Rattus norvegicus)
Cited2  (Cbp/p300-interacting transactivator, with Glu/Asp-rich carboxy-terminal domain, 2)

Genes (Mus musculus)
Cited2  (Cbp/p300-interacting transactivator, with Glu/Asp-rich carboxy-terminal domain, 2)

Genes (Homo sapiens)
CITED2  (Cbp/p300 interacting transactivator with Glu/Asp rich carboxy-terminal domain 2)


Additional Information