Calcified apoptotic vesicles from PROCR+ fibroblasts initiate heterotopic ossification.
J Extracell Vesicles
; 13(4): e12425, 2024 Apr.
Article
em En
| MEDLINE
| ID: mdl-38594791
ABSTRACT
Heterotopic ossification (HO) comprises the abnormal formation of ectopic bone in extraskeletal soft tissue. The factors that initiate HO remain elusive. Herein, we found that calcified apoptotic vesicles (apoVs) led to increased calcification and stiffness of tendon extracellular matrix (ECM), which initiated M2 macrophage polarization and HO progression. Specifically, single-cell transcriptome analyses of different stages of HO revealed that calcified apoVs were primarily secreted by a PROCR+ fibroblast population. In addition, calcified apoVs enriched calcium by annexin channels, absorbed to collagen I via electrostatic interaction, and aggregated to produce calcifying nodules in the ECM, leading to tendon calcification and stiffening. More importantly, apoV-releasing inhibition or macrophage deletion both successfully reversed HO development. Thus, we are the first to identify calcified apoVs from PROCR+ fibroblasts as the initiating factor of HO, and might serve as the therapeutic target for inhibiting pathological calcification.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ossificação Heterotópica
/
Vesículas Extracelulares
Limite:
Humans
Idioma:
En
Revista:
J Extracell Vesicles
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China
País de publicação:
Estados Unidos