Caspase-8 Deficient Osteoblastic Cells Display Alterations in Non-Apoptotic Pathways

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14310%2F22%3A00119709" target="_blank" >RIV/00216224:14310/22:00119709 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/68081715:_____/22:00557511 RIV/67985904:_____/22:00557511 RIV/00159816:_____/22:00077648 RIV/62157124:16170/22:43880201

Výsledek na webu

<a href="https://www.frontiersin.org/articles/10.3389/fcell.2022.794407/full" target="_blank" >https://www.frontiersin.org/articles/10.3389/fcell.2022.794407/full</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3389/fcell.2022.794407" target="_blank" >10.3389/fcell.2022.794407</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Caspase-8 Deficient Osteoblastic Cells Display Alterations in Non-Apoptotic Pathways

Popis výsledku v původním jazyce

Caspase-8 is the key component of the receptor-mediated (extrinsic) apoptotic pathway. Immunological localization of active caspase-8 showed its presence in osteoblasts, including non-apoptotic ones. Further in vivo exploration of caspase-8 functions in the bone is hindered by the fact that the caspase-8 knock-out is lethal prenatally. Examinations were thus performed using individual cell populations in vitro. In this study, caspase-8 was eliminated by the CRISPR/cas9 technology in MC3T3-E1 cells, the most common in vitro model of osteoblastic populations. The aim of the work was to specify the consequences of caspase-8 deficiency on non-apoptotic pathways. The impact on the osteogenic gene expression of the osteoblastic cells along with alterations in proliferation, caspase cascades and rapamycin induced autophagy response were evaluated. Osteogenic differentiation of caspase-8 deficient cells was inhibited as these cells displayed a decreased level of mineralization and lower activity of alkaline phosphatase. Among affected osteogenic genes, based on the PCR Array, major changes were observed for Ctsk, as down-regulated, and Gdf10, as up-regulated. Other significantly down-regulated genes included those coding osteocalcin, bone morphogenetic proteins (-3, -4 and -7), collagens (-1a1, -14a1) or Phex. The formation of autophagosomes was not altered in rapamycin-treated caspase-8 deficient cells, but expression of some autophagy-related genes, including Tnfsf10, Cxcr4, Dapk1 and Igf1, was significantly downregulated. These data provide new insight into the effects of caspase-8 on non-apoptotic osteogenic pathways.

Název v anglickém jazyce

Caspase-8 Deficient Osteoblastic Cells Display Alterations in Non-Apoptotic Pathways

Popis výsledku anglicky

Caspase-8 is the key component of the receptor-mediated (extrinsic) apoptotic pathway. Immunological localization of active caspase-8 showed its presence in osteoblasts, including non-apoptotic ones. Further in vivo exploration of caspase-8 functions in the bone is hindered by the fact that the caspase-8 knock-out is lethal prenatally. Examinations were thus performed using individual cell populations in vitro. In this study, caspase-8 was eliminated by the CRISPR/cas9 technology in MC3T3-E1 cells, the most common in vitro model of osteoblastic populations. The aim of the work was to specify the consequences of caspase-8 deficiency on non-apoptotic pathways. The impact on the osteogenic gene expression of the osteoblastic cells along with alterations in proliferation, caspase cascades and rapamycin induced autophagy response were evaluated. Osteogenic differentiation of caspase-8 deficient cells was inhibited as these cells displayed a decreased level of mineralization and lower activity of alkaline phosphatase. Among affected osteogenic genes, based on the PCR Array, major changes were observed for Ctsk, as down-regulated, and Gdf10, as up-regulated. Other significantly down-regulated genes included those coding osteocalcin, bone morphogenetic proteins (-3, -4 and -7), collagens (-1a1, -14a1) or Phex. The formation of autophagosomes was not altered in rapamycin-treated caspase-8 deficient cells, but expression of some autophagy-related genes, including Tnfsf10, Cxcr4, Dapk1 and Igf1, was significantly downregulated. These data provide new insight into the effects of caspase-8 on non-apoptotic osteogenic pathways.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10605 - Developmental biology

Projekt

<a href="/cs/project/GA19-14727S" target="_blank" >GA19-14727S: Specifikace osteogenního potenciálu kaspáz v kontextu kraniofaciálního vývoje</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach

Rok uplatnění

2022

Kód důvěrnosti údajů

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

Název periodika

Frontiers in Cell and Developmental Biology

ISSN

2296-634X

e-ISSN

2296-634X

Svazek periodika

10

Číslo periodika v rámci svazku

March

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

11

Strana od-do

1-11

Kód UT WoS článku

000777473600001

EID výsledku v databázi Scopus

2-s2.0-85127513684