Enhanced BMP signaling in Cathepsin K-positive tendon progenitors induces heterotopic ossification.

Mice Animals Cathepsin K / metabolism Mechanotransduction, Cellular Hedgehog Proteins Ossification, Heterotopic / metabolism Tendons / metabolism
BMP signaling Hedgehog signaling Heterotopic ossification Mechanotransduction Mouse

Journal

Biochemical and biophysical research communications
ISSN: 1090-2104
Titre abrégé: Biochem Biophys Res Commun
Pays: United States
ID NLM: 0372516

Informations de publication

Date de publication:
25 12 2023
Historique:
received: 29 08 2023
accepted: 23 10 2023
pmc-release: 25 12 2024
medline: 27 11 2023
pubmed: 11 11 2023
entrez: 10 11 2023
Statut: ppublish

Résumé

Heterotopic ossification (HO) is abnormal bone growth in soft tissues that results from injury, trauma, and rare genetic disorders. Bone morphogenetic proteins (BMPs) are critical osteogenic regulators which are involved in HO. However, it remains unclear how BMP signaling interacts with other extracellular stimuli to form HO. To address this question, using the Cre-loxP recombination system in mice, we conditionally expressed the constitutively activated BMP type I receptor ALK2 with a Q207D mutation (Ca-ALK2) in Cathepsin K-Cre labeled tendon progenitors (hereafter "Ca-Alk2:Ctsk-Cre"). Ca-Alk2:Ctsk-Cre mice were viable but they formed spontaneous HO in the Achilles tendon. Histological and molecular marker analysis revealed that HO is formed via endochondral ossification. Ectopic chondrogenesis coincided with enhanced GLI1 production, suggesting that elevated Hedgehog (Hh) signaling is involved in the pathogenesis of HO. Interestingly, focal adhesion kinase, a critical mediator for the mechanotransduction pathway, was also activated in Ca-Alk2:Ctsk-Cre mice. Our findings suggest that enhanced BMP signaling may elevate Hh and mechanotransduction pathways, thereby causing HO in the regions of the Achilles tendon.

Identifiants

DOI: 10.1016/j.bbrc.2023.149147 PMID: 37948912 PMC: PMC10952113
pubmed: 37948912
pii: S0006-291X(23)01241-X
doi: 10.1016/j.bbrc.2023.149147
pmc: PMC10952113
mid: NIHMS1972849
pii:
doi:

Substances chimiques

Cathepsin K EC 3.4.22.38
Hedgehog Proteins 0

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

149147

Subventions

Organisme : NIDCR NIH HHS
ID : R01 DE025897
Pays : United States

Informations de copyright

Copyright © 2023 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interest The authors declared no potential conflicts of interest for the research, authorship, and/or publication of this article.

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Auteurs

Hiroyuki Yamaguchi (H)

Department of Pediatrics, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.

Margaret Li (M)

Department of Pediatrics, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA; Department of Kinesiology, Rice University Wiess School of Natural Science, Houston, TX, 77005, USA.

Megumi Kitami (M)

Division of Dental Pharmacology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, 951-8514, Japan; Center for Advanced Oral Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata, 951-8514, Japan.

Sowmya Swaminathan (S)

Department of Pediatrics, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA; The College of Natural Sciences, The University of Texas at Austin, Austin, TX, 78712, USA.

Yuji Mishina (Y)

Department of Biologic and Materials Sciences & Prosthodontics, School of Dentistry, University of Michigan, Ann Arbor, MI, 48109, USA.

Yoshihiro Komatsu (Y)

Department of Pediatrics, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA; Graduate Program in Genetics and Epigenetics, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX, 77030, USA. Electronic address: Yoshihiro.Komatsu@uth.tmc.edu.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Enhanced BMP signaling in Cathepsin K-positive...
questionsmedicales.fr › Eucaryotes › Animaux › Enhanced BMP signaling in Cathepsin K-positive...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Hydrolases › Peptide hydrolases › Endopeptidases › Cysteine endopeptidases › Cathepsine K › Enhanced BMP signaling in Cathepsin K-positive...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Mécanotransduction cellulaire › Enhanced BMP signaling in Cathepsin K-positive...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Protéines Hedgehog › Enhanced BMP signaling in Cathepsin K-positive...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Ossification hétérotopique › Enhanced BMP signaling in Cathepsin K-positive...
questionsmedicales.fr › Appareil locomoteur › Tendons › Enhanced BMP signaling in Cathepsin K-positive...