Irina Kerna "The contribution of ADAM12 and CILP genes to the development of knee osteoarthritis" | University of Tartu

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Contacts of UT units

Faculty of Arts and Humanities
Faculty phone: 
+372 737 5341
Faculty address: 
Jakobi 2, rooms 116–121, 51005 Tartu
  • Dean's Office
    Faculty phone: 
    + 372 737 5341
    Faculty address: 
    Jakobi 2, rooms 116–121, 51005 Tartu
  • Institute of History and Archaeology
    Faculty phone: 
    +372 737 5651
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    Jakobi 2, 51005 Tartu
  • Institute of Estonian and General Linguistics
    Faculty phone: 
    +372 737 5221
    Faculty address: 
    Jakobi 2, 51005 Tartu
  • Institute of Philosophy and Semiotics
    Faculty phone: 
    +372 737 5314
    Faculty address: 
    Jakobi 2, rooms 309–352, 51005 Tartu
  • Institute of Cultural Research
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    Faculty address: 
    Ülikooli 16, 51003 Tartu
  • School of Theology and Religious Studies
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    +372 737 5301
    Faculty address: 
    Ülikooli 18–310, 50090 Tartu
  • College of Foreign Languages and Cultures
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    J. Liivi 4, 50409, Tartu
  • Viljandi Culture Academy
    Faculty phone: 
    +372 435 5232
    Faculty address: 
    Posti 1, 71004 Viljandi
Faculty of Social Sciences
Faculty phone: 
+372 737 5957
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Lossi 36, 51003 Tartu
  • Dean's Office
    Faculty phone: 
    + 372 737 5900
    Faculty address: 
    Lossi 36, 51003 Tartu
  • Institute of Education
    Faculty phone: 
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    Faculty address: 
    Salme 1a–29, 50103 Tartu
  • Johan Skytte Institute of Political Studies
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    Faculty address: 
    Lossi 36–301, 51003 Tartu
  • School of Economics and Business Administration
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    Narva mnt 18, 51009 Tartu
  • Institute of Psychology
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  • Institute of Biomedicine and Translational Medicine
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  • Institute of Pharmacy
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  • Institute of Clinical Medicine
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    Jakobi 5–205, 51005 Tartu
Faculty of Science and Technology
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Vanemuise 46–208, 51014 Tartu
  • Dean's Office
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  • Estonian Marine Institute
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  • Institute of Physics
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  • Institute of Mathematics and Statistics
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  • Institute of Molecular and Cell Biology
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  • Tartu Observatory
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  • Institute of Technology
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  • Youth Academy
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  • Institute of Genomics
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    Riia 23b, 51010 Tartu
  • Museum
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  • University of Tartu Natural History Museum and Botanical Garden
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    Faculty address: 
    Narva mnt 18, 51009, Tartu
  • University Office in Tallinn
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    Faculty address: 
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  • Estates Office
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    Faculty address: 
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  • Finance Office
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  • Grant Office
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    Lossi 3, III floor, 51003 Tartu
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  • Procurement Office
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  • View all other units

Irina Kerna "The contribution of ADAM12 and CILP genes to the development of knee osteoarthritis"

Date: 
23.05.2014 - 14:00 to 16:00

Thesis supervisors:
Agu Tamm, MD, PhD, DMSci, Professor, Department of Internal Medicine, University of Tartu

Kalle Kisand, MD, PhD, Department of Biomedicine, Institute of Biomedicine and Translational Medicine, University of Tartu

Opponent: Kari Pulkki, MD, PhD, FEBMB, Professor, Department of Clinical Chemistry (Laboratory Medicine),
School of Medicine University of Eastern Finland, Kuopio,
Finland Eastern Finland Laboratory Centre

Summary:
Osteoarthritis (OA) is the most common arthritic disorder, with a large number of environmental and genetic risk factors. Genetic factors have been shown to influence the dynamics and outcomes of OA, as have other OA risk factors. Currently, OA is recognised as a form of arthritis with an inflammatory component, which involves all of the joint tissues. The global burden of the disease and lack of definitive treatment, as well insufficient knowledge of several pathogenetic steps, ensure the importance of genetic research in OA. Comprehensive consideration of promising candidate genes on the mRNA and protein levels could improve our current knowledge of the disease. The aims of the present study were to perform an analysis of two OA candidate genes-ADAM12 (disintegrin and metalloproteinase domain 12) and CILP (cartilage intermediate layer protein)-on DNA-RNA-protein levels in radiographic knee OA (rKOA). The study consisted of a population-based cohort (N=437) and subjects undergoing arthroscopy (N=91), aged 32-60. The current study demonstrated that ADAM12 is associated with rKOA processes at different levels (gene and protein).

Polymorphisms of the ADAM12 gene carried the risk of rKOA. In males and females rKOA risk was associated with different variants. In both genders the risk was associated only with osteophytosis. The protein product of the ADAM12 gene (ADAM12-S) was found at higher concentrations in the late stages of the disease. The expression of ADAM12 mRNA and protein in synovia was up-regulated during synovial inflammation, especially in fibrosis.

CILP, which is thought to be a specific cartilage biomarker, was found in synovia at the mRNA and protein levels, suggesting that synovia may be an additional source of CILP production. Similarly to ADAM12, the synovial expression of CILP mRNA was found to be up-regulated in fibrotic samples. Moreover, CILP mRNA expression was down-regulated in subjects with advanced stages of joint space narrowing. Both genes demonstrated gender-specific effects on rKOA risk and synovial fibrogenesis.

The present study establishes the association of ADAM12 and CILP genes with different aspects of KOA pathogenesis, suggesting involvement of the ADAM12 gene in bone remodelling (osteophytosis), as well the role of ADAM12 and CILP genes in the development of synovial fibrosis.

Location: 
Ravila 19-1038
Event category: