Cargando…

Lysyl hydroxylase 2 mediated collagen post-translational modifications and functional outcomes

Lysyl hydroxylase 2 (LH2) is a member of LH family that catalyzes the hydroxylation of lysine (Lys) residues on collagen, and this particular isozyme has been implicated in various diseases. While its function as a telopeptidyl LH is generally accepted, several fundamental questions remain unanswere...

Descripción completa

Detalles Bibliográficos
Autores principales: Terajima, Masahiko, Taga, Yuki, Nakamura, Tomoyuki, Guo, Hou-Fu, Kayashima, Yukako, Maeda-Smithies, Nobuyo, Parag-Sharma, Kshitij, Kim, Jeong Seon, Amelio, Antonio L., Mizuno, Kazunori, Kurie, Jonathan M., Yamauchi, Mitsuo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9395344/
https://www.ncbi.nlm.nih.gov/pubmed/35995931
http://dx.doi.org/10.1038/s41598-022-18165-0
_version_ 1784771670804791296
author Terajima, Masahiko
Taga, Yuki
Nakamura, Tomoyuki
Guo, Hou-Fu
Kayashima, Yukako
Maeda-Smithies, Nobuyo
Parag-Sharma, Kshitij
Kim, Jeong Seon
Amelio, Antonio L.
Mizuno, Kazunori
Kurie, Jonathan M.
Yamauchi, Mitsuo
author_facet Terajima, Masahiko
Taga, Yuki
Nakamura, Tomoyuki
Guo, Hou-Fu
Kayashima, Yukako
Maeda-Smithies, Nobuyo
Parag-Sharma, Kshitij
Kim, Jeong Seon
Amelio, Antonio L.
Mizuno, Kazunori
Kurie, Jonathan M.
Yamauchi, Mitsuo
author_sort Terajima, Masahiko
collection PubMed
description Lysyl hydroxylase 2 (LH2) is a member of LH family that catalyzes the hydroxylation of lysine (Lys) residues on collagen, and this particular isozyme has been implicated in various diseases. While its function as a telopeptidyl LH is generally accepted, several fundamental questions remain unanswered: 1. Does LH2 catalyze the hydroxylation of all telopeptidyl Lys residues of collagen? 2. Is LH2 involved in the helical Lys hydroxylation? 3. What are the functional consequences when LH2 is completely absent? To answer these questions, we generated LH2-null MC3T3 cells (LH2KO), and extensively characterized the type I collagen phenotypes in comparison with controls. Cross-link analysis demonstrated that the hydroxylysine-aldehyde (Hyl(ald))-derived cross-links were completely absent from LH2KO collagen with concomitant increases in the Lys(ald)-derived cross-links. Mass spectrometric analysis revealed that, in LH2KO type I collagen, telopeptidyl Lys hydroxylation was completely abolished at all sites while helical Lys hydroxylation was slightly diminished in a site-specific manner. Moreover, di-glycosylated Hyl was diminished at the expense of mono-glycosylated Hyl. LH2KO collagen was highly soluble and digestible, fibril diameters were diminished, and mineralization impaired when compared to controls. Together, these data underscore the critical role of LH2-catalyzed collagen modifications in collagen stability, organization and mineralization in MC3T3 cells.
format Online
Article
Text
id pubmed-9395344
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-93953442022-08-24 Lysyl hydroxylase 2 mediated collagen post-translational modifications and functional outcomes Terajima, Masahiko Taga, Yuki Nakamura, Tomoyuki Guo, Hou-Fu Kayashima, Yukako Maeda-Smithies, Nobuyo Parag-Sharma, Kshitij Kim, Jeong Seon Amelio, Antonio L. Mizuno, Kazunori Kurie, Jonathan M. Yamauchi, Mitsuo Sci Rep Article Lysyl hydroxylase 2 (LH2) is a member of LH family that catalyzes the hydroxylation of lysine (Lys) residues on collagen, and this particular isozyme has been implicated in various diseases. While its function as a telopeptidyl LH is generally accepted, several fundamental questions remain unanswered: 1. Does LH2 catalyze the hydroxylation of all telopeptidyl Lys residues of collagen? 2. Is LH2 involved in the helical Lys hydroxylation? 3. What are the functional consequences when LH2 is completely absent? To answer these questions, we generated LH2-null MC3T3 cells (LH2KO), and extensively characterized the type I collagen phenotypes in comparison with controls. Cross-link analysis demonstrated that the hydroxylysine-aldehyde (Hyl(ald))-derived cross-links were completely absent from LH2KO collagen with concomitant increases in the Lys(ald)-derived cross-links. Mass spectrometric analysis revealed that, in LH2KO type I collagen, telopeptidyl Lys hydroxylation was completely abolished at all sites while helical Lys hydroxylation was slightly diminished in a site-specific manner. Moreover, di-glycosylated Hyl was diminished at the expense of mono-glycosylated Hyl. LH2KO collagen was highly soluble and digestible, fibril diameters were diminished, and mineralization impaired when compared to controls. Together, these data underscore the critical role of LH2-catalyzed collagen modifications in collagen stability, organization and mineralization in MC3T3 cells. Nature Publishing Group UK 2022-08-22 /pmc/articles/PMC9395344/ /pubmed/35995931 http://dx.doi.org/10.1038/s41598-022-18165-0 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Terajima, Masahiko
Taga, Yuki
Nakamura, Tomoyuki
Guo, Hou-Fu
Kayashima, Yukako
Maeda-Smithies, Nobuyo
Parag-Sharma, Kshitij
Kim, Jeong Seon
Amelio, Antonio L.
Mizuno, Kazunori
Kurie, Jonathan M.
Yamauchi, Mitsuo
Lysyl hydroxylase 2 mediated collagen post-translational modifications and functional outcomes
title Lysyl hydroxylase 2 mediated collagen post-translational modifications and functional outcomes
title_full Lysyl hydroxylase 2 mediated collagen post-translational modifications and functional outcomes
title_fullStr Lysyl hydroxylase 2 mediated collagen post-translational modifications and functional outcomes
title_full_unstemmed Lysyl hydroxylase 2 mediated collagen post-translational modifications and functional outcomes
title_short Lysyl hydroxylase 2 mediated collagen post-translational modifications and functional outcomes
title_sort lysyl hydroxylase 2 mediated collagen post-translational modifications and functional outcomes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9395344/
https://www.ncbi.nlm.nih.gov/pubmed/35995931
http://dx.doi.org/10.1038/s41598-022-18165-0
work_keys_str_mv AT terajimamasahiko lysylhydroxylase2mediatedcollagenposttranslationalmodificationsandfunctionaloutcomes
AT tagayuki lysylhydroxylase2mediatedcollagenposttranslationalmodificationsandfunctionaloutcomes
AT nakamuratomoyuki lysylhydroxylase2mediatedcollagenposttranslationalmodificationsandfunctionaloutcomes
AT guohoufu lysylhydroxylase2mediatedcollagenposttranslationalmodificationsandfunctionaloutcomes
AT kayashimayukako lysylhydroxylase2mediatedcollagenposttranslationalmodificationsandfunctionaloutcomes
AT maedasmithiesnobuyo lysylhydroxylase2mediatedcollagenposttranslationalmodificationsandfunctionaloutcomes
AT paragsharmakshitij lysylhydroxylase2mediatedcollagenposttranslationalmodificationsandfunctionaloutcomes
AT kimjeongseon lysylhydroxylase2mediatedcollagenposttranslationalmodificationsandfunctionaloutcomes
AT amelioantoniol lysylhydroxylase2mediatedcollagenposttranslationalmodificationsandfunctionaloutcomes
AT mizunokazunori lysylhydroxylase2mediatedcollagenposttranslationalmodificationsandfunctionaloutcomes
AT kuriejonathanm lysylhydroxylase2mediatedcollagenposttranslationalmodificationsandfunctionaloutcomes
AT yamauchimitsuo lysylhydroxylase2mediatedcollagenposttranslationalmodificationsandfunctionaloutcomes