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Title: | A NOVEL ROLE OF THE MECHANO-SENSING PROTEIN P130CAS IN SUPPORTING BONE HOMEOSTASIS | Authors: | ZHIHAI ZHAO | Keywords: | p130Cas, bone metabolism, mechano-sensing, NF-κB, osteocytes, RANKL | Issue Date: | 21-Aug-2014 | Citation: | ZHIHAI ZHAO (2014-08-21). A NOVEL ROLE OF THE MECHANO-SENSING PROTEIN P130CAS IN SUPPORTING BONE HOMEOSTASIS. ScholarBank@NUS Repository. | Abstract: | A VARIETY OF BIOLOGICAL EVENTS, INCLUDING INFLAMMATORY RESPONSES, ARE SUBJECT TO MECHANICAL INFLUENCE. HOWEVER, IT REMAINS LARGELY ELUSIVE HOW INFLAMMATION-RELATED SIGNALING IS MECHANICALLY MODULATED. HERE WE SHOW THAT P130CAS (CRK-ASSOCIATED SUBSTRATE, HEREAFTER REFERRED TO AS CAS), WHICH HAS PREVIOUSLY BEEN REPORTED TO ACT AS A CELLULAR MECHANO-SENSOR, PARTICIPATES IN INFLAMMATORY SIGNALING. UPON TREATMENT WITH THE INFLAMMATORY CYTOKINE TNF-A, CAS TRANSLOCATES INTO THE NUCLEUS AND INTERFERES WITH THE PHYSICAL ASSOCIATION BETWEEN THE ACETYLTRANSFERASE P300 AND NF-KB. WE FURTHER TEST IF THE MECHANOSENSING MOLECULE CAS PLAYS A ROLE IN THE RESPONSE OF OSTEOCYTES TO SHEAR FLOW. OSTEOCYTE-SPECIFIC CAS KNOCKOUT MICE EXHIBIT AN OSTEOPENIA ASSOCIATED WITH AN INCREASED OSTEOCLASTIC BONE RESORPTION BASED ON AN ENHANCED RANKL EXPRESSION DEPENDING ON NF-KB. THE RESULTS SHOW THAT THE CAS-NF-KB AXIS SUPPORTS THE NORMAL BONE METABOLISM, PROVIDING NOVEL INSIGHTS INTO THERAPEUTIC STRATEGIES FOR ATRO | URI: | http://scholarbank.nus.edu.sg/handle/10635/118736 |
Appears in Collections: | Ph.D Theses (Open) |
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