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Researchers
  • Dr.  Mona Dvir-Ginzberg
 
BSc- Life Sciences, Ben-Gurion University
PhD – BioMedical Engineering, Ben-Gurion University
Post-Doctoral Fellow (NIAMS), National Institutes of Health
 

 

Research Interests
 


Skeletal mobility is largely dependent on the function of our joints. The thin hyaline cartilage layer covering our bones form cushions that allow us to comfortably perform all types of physical activities. Aside from these functions, healthy cartilage protects bones from erosion, by functioning as a shock absorber during moderate or intense activity. 
Chondrocytes, which occupy cartilage, are responsible for building cartilage tissue and laying the foundation of the forming skeleton during early stages of development. 

 
 
 
 
With age however, chondrocytes rapidly loose the ability to repair the tissue properly upon insults and enter senescence. The tissue thus is thus prone to develop osteoarthritis (OA), especially upon trauma or when subject to abnormal biophysical stress due to anatomical and physical changes. Progressive erosion of articular cartilage, seen during OA, leads to pain-dysfunction and holds significant individual and socio-economic consequences.
 
 
 

 
 
 
The Laboratory of Cartilage Biology headed by Dr. Mona Dvir-Ginzberg is engaged in investigating cartilage biology during Aging and Development.
 
Investigations aim to delineate epigenetic changes that influence systemic RNA and protein expression patterns and subsequently harbor a diseased cell phenotype. Of particular interest, are the NAD-dependent deacetylases called Sirtuins, which are capable of sensing the cells energy status and affecting its metabolic state. Our recent publications support that Sirt1, a member of the sirtuin family, is cleaved during pro-inflammatory stress, thus impairing its epigenetic activity in the cell. 
 
Interestingly, healthy articular cartilage shows enhanced Sirt1 activity and high levels of protein expression. This supports that Sirt1 is required for normal cartilage maintenance during adulthood. Sirt1 may also participate in endochondral development and skeletal growth, which is an additional facet being explored in the Lab.
 
 



Research Projects

 

(a) Elucidating the mechanism by which sirtuins regulate cartilage ECM expression in human chondrocytes.
(b) Investigating the role of sirtuins in intervertebral disc degeneration.
(c) Investigation of Sirtuins in human chondrocyte apoptosis under inflammatory stress.
(d) Characterizing Sirt1 as a potential biomarker for OA predisposition (DBOARD consortium, http://www.d-board.eu/dboard/index.aspx).
(e) Understanding the physiological and biochemical impact of Sirt1 cleavage.

Lab Members



 

 





Christopher Smith, visiting Post-Doctoral Fellow
Tahsin Younis, DMD, MSc Student
Matan Harat, MD Student

 

Alumni Members 

 

Hanna Oppenheimer
Hadar Meir
Michal Bar Oz
Louisa Ben Aderet
Yutti Daitch
Israel Schwartz
Aviad Vilensky

 

 

Recent publications

 

2010
Gagarina V., Gabay O., Dvir-Ginzberg M., Lee E.J., Brady J.K., Quon M.J., Hall D.J. SirT1 enhances survival of human osteoarthritic chondrocytes by repressing PTP1B and activating the IGF receptor pathway. Arthritis and Rheumatology. 62: 1383 – 92. 2010.
 
 
2011
 
Ofek O., Attar-Namdar M., Kram V., Dvir-Ginzberg M., Mechoulam R., Zimmer A., Frenkel B., Shohami E., Bab I.. CB2 cannabinoid receptor targets mitogenic Gi protein-cyclin D1 axis in osteoblasts. J Bone Miner Res. 26:308-16. 2011.
 
Dvir-Ginzberg M., Gagarina V., Lee E.J., Gabay O., Booth R. and Hall D.J.. TNFa-mediated cleavage and inactivation of SirT1 in human chondrocytes. Arthritis and Rheumatology63:2363-73. 2011. Supplementary Data
 
2012
 
Oppenheimer H., Gabay O., Meir H., Haze A., Kandel L., Liebergall M., Gagarina V., Lee E.J., Dvir-Ginzberg M.. 75-kDa Sirtuin 1 blocks tumor necrosis factor α-mediated apoptosis in human osteoarthritic chondrocytes. Arthritis and Rheumatology. 64:718-28. 2012. Supplementary Data
 
Gabay O., Oppenheimer H., Meir H., Zaal K., Sanchez C., Dvir-Ginzberg M. Increased apoptotic chondrocytes in articular cartilage from adult heterozygous SirT1 mice. Ann Rheum Dis. 71:613-6. 2012.
 
2013
 
Dvir-Ginzberg M., Steinmeyer J.Towards elucidating the role of SirT1 in osteoarthritis. Frontiers in Bioscience. 18: 343-355. 2013.
 
Gabay O., Sanchez C., Dvir-Ginzberg M., Gagarina V., Zaal K.J., Song Y., He X.H., McBurney M.W.. Sirt1 enzymatic activity is required for cartilage homeostasis in vivoArthritis and Rheumatology. 65:159-66. 2013.
 
2014
 
Oppenheimer H, Kumar A, Meir H, Schwartz I, Zini A, Haze A, Kandel L, Mattan Y, Liebergall M, Dvir-Ginzberg M. Set7/9 impacts COL2A1 expression through binding and repression of SirT1 histone deacetylation. J Bone Miner Res. 29(2):348-60. 2014.
 
Dvir-Ginzberg M, Reich E. Chopping off the chondrocyte proteome. Biomarkers. 2014 Sep 2:1-7.
 
2015 
 
Ben-Aderet L, Merquiol E, Fahham D, Kumar A, Reich E, Ben-Nun Y, Kandel L, Haze A, Liebergall M, Kosińska MK, Steinmeyer J, Turk B, Blum G, Dvir-Ginzberg M. Detecting cathepsin activity in human osteoarthritis via activity-based probes.
Arthritis Res Ther. 2015; 20;17:69.
 
2016
 
Bar Oz M, Kumar A, Elayyan J, Reich E, Binyamin M, Kandel L, Liebergall M, Steinmeyer J, Lefebvre V, Dvir-Ginzberg M. Acetylation reduces SOX9 nuclear entry and ACAN gene transactivation in human chondrocytes. Aging Cell 2016 Feb 22. doi: 10.1111/acel.12456. [Epub ahead of print]
 
Lefebvre V, Dvir-Ginzberg M.SOX9 and the many facets of its regulation in the chondrocyte lineage. Connect Tissue Res. 2016 Apr 29.  Review link
2017
 
Elayyan J, Lee EJ, Gabay O, Smith CA, Qiq O, Reich E, Mobasheri A, Henrotin Y, Kimber SJ, Dvir-Ginzberg M.LEF1-mediated MMP13 gene expression is repressed by SIRT1 in human chondrocytes. FASEB J. 2017 Apr 7. doi: 10.1096/fj.201601253R.
PMID: 28389425
Sanchez C, Bay-Jensen AC, Pap T, Dvir-Ginzberg M, Quasnichka H, Barrett-Jolley R, Mobasheri A, Henrotin Y. Chondrocyte secretome: a source of novel insights and exploratory biomarkers of osteoarthritis.
Osteoarthritis Cartilage. 2017. doi: 10.1016/j.joca.2017.02.797. Review.
PMID: 28232143
 
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