RGD Reference Report - Ultrasound stimulates MMP-13 expression through p38 and JNK pathway in osteoblasts. - Rat Genome Database

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Ultrasound stimulates MMP-13 expression through p38 and JNK pathway in osteoblasts.

Authors: Chiu, YC  Huang, TH  Fu, WM  Yang, RS  Tang, CH 
Citation: Chiu YC, etal., J Cell Physiol. 2008 May;215(2):356-65.
RGD ID: 2296055
Pubmed: PMID:17941091   (View Abstract at PubMed)
DOI: DOI:10.1002/jcp.21322   (Journal Full-text)

It has been shown that ultrasound (US) stimulation accelerates fracture healing, bone maturation, and remodeling in the animal models and in clinical studies. One of the major factor involves in remodeling process is matrix metalloproteinases (MMPs) such as MMP-13 that has been shown to degrade the native interstitial collagens in several tissues. Here we found that US stimulation increased the secretion of MMP-13 in cultured rat osteoblasts, as shown by zymographic analysis. US stimulation also increased the mRNA level of MMP-13, c-Fos, and c-Jun. Cycloheximide (an inhibitor of protein translocation) and actinomycin D (an inhibitor of gene transcription) did not inhibit the MMP-13, c-Fos, and c-Jun mRNA expression, suggesting that such expression does not require de novo protein synthesis and not change their stabilities. p38 inhibitor, SB203580 or JNK inhibitor, SP600125 but not ERK inhibitor, PD98059 attenuated the US-induced MMP-13, c-Fos, and c-Jun expression; these results were further substantiated by transfecting with the dominant negative mutants of p38 or JNK. The binding of c-Fos and c-Jun to the AP-1 element on the MMP-13 promoter and the enhancement of AP-1 luciferase activity was enhanced by US stimulation. Taken together, our results provide evidence that US stimulation increases MMP-13 expression through p38 and JNK signaling pathway to regulate bone remodeling.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein catabolic process  IDA 2296055 RGD 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
extracellular space  IDA 2296055 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
metalloendopeptidase activity  IDA 2296055 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mmp13  (matrix metallopeptidase 13)


Additional Information