Increased collagen crosslinking in stiff clubfoot tissue: Implications for the improvement of therapeutic strategies

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F21%3A10433646" target="_blank" >RIV/00216208:11110/21:10433646 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11130/21:10433646

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=vBsmeKie9P" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=vBsmeKie9P</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/ijms222111903" target="_blank" >10.3390/ijms222111903</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Increased collagen crosslinking in stiff clubfoot tissue: Implications for the improvement of therapeutic strategies

Popis výsledku v původním jazyce

Congenital clubfoot is a complex musculoskeletal deformity, in which a stiff, contracted tissue forms in the medial part of the foot. Fibrotic changes are associated with increased collagen deposition and lysyl oxidase (LOX)-mediated crosslinking, which impair collagen degradation and increase the tissue stiffness. First, we studied collagen deposition, as well as the expression of colla-gen and the amount of pyridinoline and deoxypyridinoline crosslinks in the tissue of relapsed clubfoot by immunohistochemistry, real-time PCR, and enzyme-linked immunosorbent assay (ELISA). We then isolated fibroblast-like cells from the contracted tissue to study the potential inhibition of these processes in vitro. We assessed the effects of a LOX inhibitor, β-aminopropionitrile (BAPN), on the cells by a hydroxyproline assay, ELISA, and Second Harmonic Generation imaging. We also evaluated the cell-mediated contraction of extracellular matrix in 3D cell-populated collagen gels. For the first time, we have confirmed significantly increased crosslinking and excessive collagen type I deposition in the clubfoot-contracted tissue. We successfully reduced these processes in vitro in a dose-dependent manner with 10-40 µg/mL of BAPN, and we observed an increasing trend in the inhibition of the cell-mediated contraction of collagen gels. The in vitro inhibitory effects indi-cate that BAPN has good potential for the treatment of relapsed and resistant clubfeet.

Název v anglickém jazyce

Increased collagen crosslinking in stiff clubfoot tissue: Implications for the improvement of therapeutic strategies

Popis výsledku anglicky

Congenital clubfoot is a complex musculoskeletal deformity, in which a stiff, contracted tissue forms in the medial part of the foot. Fibrotic changes are associated with increased collagen deposition and lysyl oxidase (LOX)-mediated crosslinking, which impair collagen degradation and increase the tissue stiffness. First, we studied collagen deposition, as well as the expression of colla-gen and the amount of pyridinoline and deoxypyridinoline crosslinks in the tissue of relapsed clubfoot by immunohistochemistry, real-time PCR, and enzyme-linked immunosorbent assay (ELISA). We then isolated fibroblast-like cells from the contracted tissue to study the potential inhibition of these processes in vitro. We assessed the effects of a LOX inhibitor, β-aminopropionitrile (BAPN), on the cells by a hydroxyproline assay, ELISA, and Second Harmonic Generation imaging. We also evaluated the cell-mediated contraction of extracellular matrix in 3D cell-populated collagen gels. For the first time, we have confirmed significantly increased crosslinking and excessive collagen type I deposition in the clubfoot-contracted tissue. We successfully reduced these processes in vitro in a dose-dependent manner with 10-40 µg/mL of BAPN, and we observed an increasing trend in the inhibition of the cell-mediated contraction of collagen gels. The in vitro inhibitory effects indi-cate that BAPN has good potential for the treatment of relapsed and resistant clubfeet.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30106 - Anatomy and morphology (plant science to be 1.6)

Projekt

<a href="/cs/project/LM2015062" target="_blank" >LM2015062: Národní infrastruktura pro biologické a medicínské zobrazování</a><br>

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

International Journal of Molecular Sciences

ISSN

1661-6596

e-ISSN

—

Svazek periodika

22

Číslo periodika v rámci svazku

21

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

18

Strana od-do

11903

Kód UT WoS článku

000719119700001

EID výsledku v databázi Scopus

2-s2.0-85118249737