Impact of FasL Stimulation on Sclerostin Expression and Osteogenic Profile in IDG-SW3 Osteocytes

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985904%3A_____%2F21%3A00546149" target="_blank" >RIV/67985904:_____/21:00546149 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/62157124:16170/21:43879165

Výsledek na webu

<a href="https://www.mdpi.com/2079-7737/10/8/757" target="_blank" >https://www.mdpi.com/2079-7737/10/8/757</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/biology10080757" target="_blank" >10.3390/biology10080757</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Impact of FasL Stimulation on Sclerostin Expression and Osteogenic Profile in IDG-SW3 Osteocytes

Popis výsledku v původním jazyce

FasL used to be considered as a classical ligand triggering cell death (apoptosis) via its receptor, Fas and thefollowing caspase cascade. As such, it is known to be involved in regulation within the bone. Recently, however, the knowledge has expanded about the non-apoptotic and caspase-independent engagement of the Fas/FasL pathway. The present investigation identified that stimulation of osteocytic IDG-SW3 cells by FasL leads to a dramatic decrease in expression of the major osteocytic marker, sclerostin. Additionally, other key components of the osteogenic pathways were impacted, notably in a caspase-independent manner. Such findings are of importance for basic biology as well as biomedical applications since osteocytes are the major population within adult bones and Fas signalling is one of therapeutical targets, e.g., in the anti-osteoporotic treatment. The Fas ligand (FasL) is known from programmed cell death, the immune system, and recently also from bone homeostasis. As such, Fas signalling is a potential target of anti-osteoporotic treatment based on the induction of osteoclastic cell death. Less attention has been paid to osteocytes, although they represent the majority of cells within the mature bone and are the key regulators. To determine the impact of FasL stimulation on osteocytes, differentiated IDG-SW3 cells were challenged by FasL, and their osteogenic expression profiles were evaluated by a pre-designed PCR array. Notably, the most downregulated gene was the one for sclerostin, which is the major marker of osteocytes and a negative regulator of bone formation. FasL stimulation also led to significant changes (over 10-fold) in the expression of other osteogenic markers: Gdf10, Gli1, Ihh, Mmp10, and Phex. To determine whether these alterations involved caspase-dependent or caspase-independent mechanisms, the IDG-SW3 cells were stimulated by FasL with and without a caspase inhibitor: Q-VD-OPh. The alterations were also detected in the samples treated by FasL along with Q-VD-OPh, pointing to the caspase-independent impact of FasL stimulation. These results contribute to an understanding of the recently emerging pleiotropic effects of Fas/FasL signalling and specify its functions in bone cells.

Název v anglickém jazyce

Impact of FasL Stimulation on Sclerostin Expression and Osteogenic Profile in IDG-SW3 Osteocytes

Popis výsledku anglicky

FasL used to be considered as a classical ligand triggering cell death (apoptosis) via its receptor, Fas and thefollowing caspase cascade. As such, it is known to be involved in regulation within the bone. Recently, however, the knowledge has expanded about the non-apoptotic and caspase-independent engagement of the Fas/FasL pathway. The present investigation identified that stimulation of osteocytic IDG-SW3 cells by FasL leads to a dramatic decrease in expression of the major osteocytic marker, sclerostin. Additionally, other key components of the osteogenic pathways were impacted, notably in a caspase-independent manner. Such findings are of importance for basic biology as well as biomedical applications since osteocytes are the major population within adult bones and Fas signalling is one of therapeutical targets, e.g., in the anti-osteoporotic treatment. The Fas ligand (FasL) is known from programmed cell death, the immune system, and recently also from bone homeostasis. As such, Fas signalling is a potential target of anti-osteoporotic treatment based on the induction of osteoclastic cell death. Less attention has been paid to osteocytes, although they represent the majority of cells within the mature bone and are the key regulators. To determine the impact of FasL stimulation on osteocytes, differentiated IDG-SW3 cells were challenged by FasL, and their osteogenic expression profiles were evaluated by a pre-designed PCR array. Notably, the most downregulated gene was the one for sclerostin, which is the major marker of osteocytes and a negative regulator of bone formation. FasL stimulation also led to significant changes (over 10-fold) in the expression of other osteogenic markers: Gdf10, Gli1, Ihh, Mmp10, and Phex. To determine whether these alterations involved caspase-dependent or caspase-independent mechanisms, the IDG-SW3 cells were stimulated by FasL with and without a caspase inhibitor: Q-VD-OPh. The alterations were also detected in the samples treated by FasL along with Q-VD-OPh, pointing to the caspase-independent impact of FasL stimulation. These results contribute to an understanding of the recently emerging pleiotropic effects of Fas/FasL signalling and specify its functions in bone cells.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10601 - Cell biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2021

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Biology

ISSN

2079-7737

e-ISSN

2079-7737

Svazek periodika

10

Číslo periodika v rámci svazku

8

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

13

Strana od-do

757

Kód UT WoS článku

000688952800001

EID výsledku v databázi Scopus

2-s2.0-85112471275