Thesis supervisor: Beáta Albert
Location of studies (in Hungarian): Sapientia Hungarian University of Transylvania Abbreviation of location of studies: EMTE
Description of the research topic:
NP plays an important role in maintaining the biomechanical properties of the spine such that in youth the healthy NP is rich in large, vacuolated notochordal cells (NCs) and possesses a proteoglycan rich ECM. However, NCs observed during childhood are gradually replaced by small chondrocyte-like cells (CLCs) by early adolescence in humans, a NP cellular phenotype o en associated with disc degeneration. The degenerative disc NP is a catabolic phenotype representing a failure of homeostatic regulation of the microenvironment with the increased expression of pro-in ammatory cytokines and matrix metalloproteinases (MMPs) leading to progressive cell death, loss of proteoglycan content and development of an inferior, brocartilaginous extra-cellular matrix (ECM). is a ects IVD structural integrity, compromising its biomechanical properties often leading to pain, neurological compromise and disability.
More recently, Wnt family members have been found to be involved in regulating skeletal development. Wnt proteins are important signaling molecules that have been shown to regulate cell proliferation and differentiation during embryonic development and tumor formation. Studies carried out in chick have shown that ectopic Wnt5a expression delays chondrocyte differentiation, whereas ectopicWnt4 expression promotes chondrocyte differentiation. However, direct evidence to show that endogenous Wnt gene function is required for chondrocyte proliferation or differentiation is lacking. Several controversies exist in the literature today regarding the mechanisms by which Wnt proteins signal. Much of the conflicting data, however, can be attributed to the variety of cellular and organismal systems studied coupled with the previous lack of soluble, active Wnt proteins.
However, there have been no reports on the role of Wnt/b-catenin signals in IVD cells or on the impact of Wnt/b-catenin signals on the metabolism of IVD cells, and as a result the degenerative process remains poorly characterized. Therefore, it is expected that the clarification of the mechanisms controlling Wnt/b-catenin signals (inhibition and activation) as well as the mechanism of Wnt/b-catenin transcriptional activation will clarify disc differentiation and the subsequent degenerative IVD process.
The aim of the study is to explore the transcriptome profile of the IVD cells, performing complex microarray studies from human surgical samples. Human mRNA expression studies will be performed on an Agilent microarray platform using adult nucleus pulposus samples. We will use normal IVD disc expression profile as control, downloaded from microarray databases. Expression differences will be validated with quantitative real-time RT-PCR technique. Transcriptome expression data will be statistically analysed applying hierarchial clustering and robust non-parametric tests. Pathway analyses will be performed using an integrative bioinformatic approach (e.g. GeneSpring, Ingenuity Pathway Analysis) to identify the key molecular elements of the IVD degeneration. Results of the comparative transcriptional profiling studies help us to understand the pathogenesis of IVD degeneration providing the chance to find new molecular targets for the future development of an effective systemic therapy and early diagnostic tools.
Recommended language skills (in Hungarian): English Number of students who can be accepted: 1
Deadline for application: 2019-05-31
2024. IV. 17. ODT ülés Az ODT következő ülésére 2024. június 14-én, pénteken 10.00 órakor kerül sor a Semmelweis Egyetem Szenátusi termében (Bp. Üllői út 26. I. emelet).
Login
