Transcript-dependent effects of the CALCA gene on the progression of post-traumatic osteoarthritis in mice

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Transcript-dependent effects of the CALCA gene on the progression of post-traumatic osteoarthritis in mice. / Jiang, Shan; Xie, Weixin; Knapstein, Paul Richard; Donat, Antonia; Albertsen, Lilly-Charlotte; Sevecke, Jan; Erdmann, Cordula; Appelt, Jessika; Fuchs, Melanie; Hildebrandt, Alexander; Maleitzke, Tazio; Frosch, Karl-Heinz; Baranowsky, Anke; Keller, Johannes.

in: COMMUN BIOL, Jahrgang 7, Nr. 1, 23.02.2024, S. 223.

Publikationen: SCORING: Beitrag in Fachzeitschrift/ZeitungSCORING: ZeitschriftenaufsatzForschungBegutachtung

Harvard

Jiang, S, Xie, W, Knapstein, PR, Donat, A, Albertsen, L-C, Sevecke, J, Erdmann, C, Appelt, J, Fuchs, M, Hildebrandt, A, Maleitzke, T, Frosch, K-H, Baranowsky, A & Keller, J 2024, 'Transcript-dependent effects of the CALCA gene on the progression of post-traumatic osteoarthritis in mice', COMMUN BIOL, Jg. 7, Nr. 1, S. 223. https://doi.org/10.1038/s42003-024-05889-0

APA

Jiang, S., Xie, W., Knapstein, P. R., Donat, A., Albertsen, L-C., Sevecke, J., Erdmann, C., Appelt, J., Fuchs, M., Hildebrandt, A., Maleitzke, T., Frosch, K-H., Baranowsky, A., & Keller, J. (2024). Transcript-dependent effects of the CALCA gene on the progression of post-traumatic osteoarthritis in mice. COMMUN BIOL, 7(1), 223. https://doi.org/10.1038/s42003-024-05889-0

Vancouver

Bibtex

@article{16583b07af6d45dca04701e2942dfc95,
title = "Transcript-dependent effects of the CALCA gene on the progression of post-traumatic osteoarthritis in mice",
abstract = "Osteoarthritis represents a chronic degenerative joint disease with exceptional clinical relevance. Polymorphisms of the CALCA gene, giving rise to either a procalcitonin/calcitonin (PCT/CT) or a calcitonin gene-related peptide alpha (αCGRP) transcript by alternative splicing, were reported to be associated with the development of osteoarthritis. The objective of this study was to investigate the role of both PCT/CT and αCGRP transcripts in a mouse model of post-traumatic osteoarthritis (ptOA). WT, αCGRP-/- and CALCA-/- mice were subjected to anterior cruciate ligament transection (ACLT) to induce ptOA of the knee. Mice were sacrificed 4 and 8 weeks post-surgery, followed by micro-CT and histological evaluation. Here we show that the expression of both PCT/CT and αCGRP transcripts is induced in ptOA knees. CALCA-/- mice show increased cartilage degeneration and subchondral bone loss with elevated osteoclast numbers compared to αCGRP-/- and WT mice. Osteophyte formation is reduced to the same extent in CALCA-/- and αCGRP-/- mice compared to WT controls, while a reduced synovitis score is noticed exclusively in mice lacking CALCA. Our data show that expression of the PCT/CT transcript protects from the progression of ptOA, while αCGRP promotes osteophyte formation, suggesting that CALCA-encoded peptides may represent novel targets for the treatment of ptOA.",
author = "Shan Jiang and Weixin Xie and Knapstein, {Paul Richard} and Antonia Donat and Lilly-Charlotte Albertsen and Jan Sevecke and Cordula Erdmann and Jessika Appelt and Melanie Fuchs and Alexander Hildebrandt and Tazio Maleitzke and Karl-Heinz Frosch and Anke Baranowsky and Johannes Keller",
note = "{\textcopyright} 2024. The Author(s).",
year = "2024",
month = feb,
day = "23",
doi = "10.1038/s42003-024-05889-0",
language = "English",
volume = "7",
pages = "223",
journal = "COMMUN BIOL",
issn = "2399-3642",
publisher = "NATURE PUBLISHING GROUP",
number = "1",

}

RIS

TY - JOUR

T1 - Transcript-dependent effects of the CALCA gene on the progression of post-traumatic osteoarthritis in mice

AU - Jiang, Shan

AU - Xie, Weixin

AU - Knapstein, Paul Richard

AU - Donat, Antonia

AU - Albertsen, Lilly-Charlotte

AU - Sevecke, Jan

AU - Erdmann, Cordula

AU - Appelt, Jessika

AU - Fuchs, Melanie

AU - Hildebrandt, Alexander

AU - Maleitzke, Tazio

AU - Frosch, Karl-Heinz

AU - Baranowsky, Anke

AU - Keller, Johannes

N1 - © 2024. The Author(s).

PY - 2024/2/23

Y1 - 2024/2/23

N2 - Osteoarthritis represents a chronic degenerative joint disease with exceptional clinical relevance. Polymorphisms of the CALCA gene, giving rise to either a procalcitonin/calcitonin (PCT/CT) or a calcitonin gene-related peptide alpha (αCGRP) transcript by alternative splicing, were reported to be associated with the development of osteoarthritis. The objective of this study was to investigate the role of both PCT/CT and αCGRP transcripts in a mouse model of post-traumatic osteoarthritis (ptOA). WT, αCGRP-/- and CALCA-/- mice were subjected to anterior cruciate ligament transection (ACLT) to induce ptOA of the knee. Mice were sacrificed 4 and 8 weeks post-surgery, followed by micro-CT and histological evaluation. Here we show that the expression of both PCT/CT and αCGRP transcripts is induced in ptOA knees. CALCA-/- mice show increased cartilage degeneration and subchondral bone loss with elevated osteoclast numbers compared to αCGRP-/- and WT mice. Osteophyte formation is reduced to the same extent in CALCA-/- and αCGRP-/- mice compared to WT controls, while a reduced synovitis score is noticed exclusively in mice lacking CALCA. Our data show that expression of the PCT/CT transcript protects from the progression of ptOA, while αCGRP promotes osteophyte formation, suggesting that CALCA-encoded peptides may represent novel targets for the treatment of ptOA.

AB - Osteoarthritis represents a chronic degenerative joint disease with exceptional clinical relevance. Polymorphisms of the CALCA gene, giving rise to either a procalcitonin/calcitonin (PCT/CT) or a calcitonin gene-related peptide alpha (αCGRP) transcript by alternative splicing, were reported to be associated with the development of osteoarthritis. The objective of this study was to investigate the role of both PCT/CT and αCGRP transcripts in a mouse model of post-traumatic osteoarthritis (ptOA). WT, αCGRP-/- and CALCA-/- mice were subjected to anterior cruciate ligament transection (ACLT) to induce ptOA of the knee. Mice were sacrificed 4 and 8 weeks post-surgery, followed by micro-CT and histological evaluation. Here we show that the expression of both PCT/CT and αCGRP transcripts is induced in ptOA knees. CALCA-/- mice show increased cartilage degeneration and subchondral bone loss with elevated osteoclast numbers compared to αCGRP-/- and WT mice. Osteophyte formation is reduced to the same extent in CALCA-/- and αCGRP-/- mice compared to WT controls, while a reduced synovitis score is noticed exclusively in mice lacking CALCA. Our data show that expression of the PCT/CT transcript protects from the progression of ptOA, while αCGRP promotes osteophyte formation, suggesting that CALCA-encoded peptides may represent novel targets for the treatment of ptOA.

U2 - 10.1038/s42003-024-05889-0

DO - 10.1038/s42003-024-05889-0

M3 - SCORING: Journal article

C2 - 38396204

VL - 7

SP - 223

JO - COMMUN BIOL

JF - COMMUN BIOL

SN - 2399-3642

IS - 1

ER -