Κατεύθυνση Εφαρμογές της Βιολογίας στην Ιατρική
Library of the School of Science

2019-11-25

2019

Pateraki Evangelia

Ιωάννης Τρουγκάκος, Καθηγητής Βιολογίας Ζωικού Κυττάρου & Ηλεκτρονικής Μικροσκοπίας, Τμήμα Βιολογίας, ΕΚΠΑ
Δημήτρης Κλέτσας, Α΄Ερευνητής, ΕΚΕΦΕ Δημόκριτος
Μαριάννα Αντωνέλου, Επίκουρη Καθηγήτρια Βιολογίας Ζωικού Κυττάρου, Τμήμα Βιολογίας, ΕΚΠΑ

Επίδραση φαρμακευτικών παρεμβάσεων στην ομοιοστασία κυττάρων του μεσοσπονδύλιου δίσκου

Greek

Influence of medication interventions on intervertebral disc cell homeostasis

The intervertebral discs lie between the vertebral bodies, linking them together. They consist from the inside to the outside of the nucleus puplosus and the annulus fibrosus, and are surrounded by the vertebral endplates. The components of the extracellular matrix of the tissue are in a dynamic equilibrium, that is, they are constantly synthesized and degraded. A particularly important feature of intervertebral discs is their reduced vascularity, leading to a reduced transportation into the disc, as well as a reduced clearance at the metabolism’s byproducts. The difficulty of metabolism’s wastes removal from the tissue can cause them to accumulate and lead to disruption of homeostasis and degeneration of the intervertebral disc.
Furthermore, chemotherapy is a common treatment resime for tumours in several tissues. However, the effect of chemotherapeutic drugs on intervertebral disc cells has not been adequately investigated. For this reason, the effect of three cytotoxic compounds (doxorubicin, cisplatin and zoledronic acid) in bovine nucleus pulposus cells of the intervertebral disc was studied.
All three compounds studied exhibit a dose-dependent cytotoxicity based on the MTT assay, but also by the direct determination of active cells’s number, while they also affect intracellular ROS levels. Specifically, zoledronic acid, under these experimental conditions, doesn’t cause DNA damage and does not induce apoptosis via activation of caspase-3. However, although zoledronic acid does not affect the expression of aggrecan at mRNA level, it causes a decrease in the expression of collagen II, a major component of the extracellular matrix of the nucleus pulposus. At the same time, it causes an increase in the expression of catabolic enzymes, such as MMP-13 and ADAMTS-5. In addition, an increase in pro-inflammatory factors such as IL-1β was observed.
These results suggest that exposure of the nucleus pulposus to zoledronic acid, causes an increase in the expression of factors that degrade the extracellular matrix of the disc thereby disrupting tissue homeostasis leading to the degeneration of intervertebral disc.

Science

Ιntervertebral disc, Νucleus puplosus, Chemotherapy, Degeneration of the intervertebral disc, Zoledronic acid

Yes

2

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https://pergamos.lib.uoa.gr/uoa/dl/object/2886289