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

Result code in 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>

Alternative codes found

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

Result on the web

<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>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10605 - Developmental biology

Project

<a href="/en/project/GA19-14727S" target="_blank" >GA19-14727S: Specification of osteogenic potential of caspases in context of craniofacial development</a><br>

Continuities

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

Publication year

2022

Confidentiality

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

Name of the periodical

Frontiers in Cell and Developmental Biology

ISSN

2296-634X

e-ISSN

2296-634X

Volume of the periodical

10

Issue of the periodical within the volume

March

Country of publishing house

CH - SWITZERLAND

Number of pages

11

Pages from-to

1-11

UT code for WoS article

000777473600001

EID of the result in the Scopus database

2-s2.0-85127513684