Faculty, Staff and Student Publications

Language

English

Publication Date

12-25-2023

Journal

Biochemical and Biophysical Research Communications

DOI

10.1016/j.bbrc.2023.149147

PMID

37948912

PMCID

PMC10952113

PubMedCentral® Posted Date

12-25-2024

PubMedCentral® Full Text Version

Author MSS

Abstract

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.

Keywords

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

Published Open-Access

yes

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