Related Experiment Video
Updated: Jun 21, 2026

Real-Time Imaging of CCL5-Induced Migration of Periosteal Skeletal Stem Cells in Mice
Published on: September 16, 2020
Identification of CITED2 as a negative regulator of fracture healing
Jonathan Y Lee1, Peter J Taub, Liang Wang
1Leni and Peter W. May Department of Orthopaedics, Mount Sinai School of Medicine, NY, USA.
Abstract:
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.
Related Concept Videos
Growth of Cartilage and Bone Tissue
Fractures: Bone Repair
Minor fractures with no bone displacement are treated by immobilizing the fractured bone using a cast or splint. However, in the case of fractures with displaced bones, the broken bones are repositioned before immobilization to ensure successful healing without deformation and loss of function. The realignment of fractured bone ends is performed through a process called reduction. If the procedure...
Regulated Protein Degradation
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Cadherins in Tissue Organization
Cell Sorting During Development
Cell sorting plays an...
NF-κB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...

