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Increased Collagen Crosslinking in Stiff Clubfoot Tissue: Implications for the Improvement of Therapeutic Strategies
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SYSNO ASEP 0549781 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Increased Collagen Crosslinking in Stiff Clubfoot Tissue: Implications for the Improvement of Therapeutic Strategies Tvůrce(i) Knitlová, Jarmila (FGU-C) RID, ORCID
Doubková, Martina (FGU-C) ORCID, RID
Eckhardt, Adam (FGU-C) RID, ORCID
Ošťádal, M. (CZ)
Musílková, Jana (FGU-C) RID, ORCID
Bačáková, Lucie (FGU-C) RID, ORCID
Novotný, T. (CZ)Číslo článku 11903 Zdroj.dok. International Journal of Molecular Sciences. - : MDPI
Roč. 22, č. 21 (2021)Poč.str. 18 s. Jazyk dok. eng - angličtina Země vyd. CH - Švýcarsko Klíč. slova relapsed clubfoot ; congenital idiopathic Talipes equinovarus ; collagen ; contraction ; crosslinking ; beta-aminopropionitrile (BAPN) ; fibrosis Vědní obor RIV FI - Traumatologie, ortopedie Obor OECD Orthopaedics CEP NV17-31564A GA MZd - Ministerstvo zdravotnictví LM2015062 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Způsob publikování Open access Institucionální podpora FGU-C - RVO:67985823 UT WOS 000719119700001 EID SCOPUS 85118249737 DOI 10.3390/ijms222111903 Anotace 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 collagen 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, beta-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 mu g/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 indicate that BAPN has good potential for the treatment of relapsed and resistant clubfeet. Pracoviště Fyziologický ústav Kontakt Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Rok sběru 2022 Elektronická adresa https://www.mdpi.com/1422-0067/22/21/11903
Počet záznamů: 1