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Calcified apoptotic vesicles from PROCR + fibroblasts initiate heterotopic ossification

Year: 2024
Type: article
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.
DOI: 10.1002/jev2.12425
Authors: Jianfei Yan, Bo Gao, Chenyu Wang, Weicheng Lu, Wenpin Qin, Xiaoxiao Han, Yingying Liu, Tao Li, Zhenxing Guo, Tao Ye, Qianqian Wan, Haoqing Xu, Junjun Kang, Naining Lu, Changhe Gao, Zixuan Qin, Chi Yang, Jisi Zheng, Pei Shen, Lina Niu, Weiguo Zou, Kai Jiao
Institutions: Air Force Medical University, Xijing Hospital, Stomatology Hospital, Xi'an Jiaotong University, Northwest University, Shanghai Jiao Tong University, Shanghai Ninth People's Hospital, Chinese Academy of Sciences, Center for Excellence in Molecular Cell Science, University of Chinese Academy of Sciences, State Key Laboratory of Cell Biology
Language: English
Subfield: Rheumatology
Field: Medicine
Open Access status: gold
Estimated APC paid: $4,410
OpenAlex ID: W4394685013
FWCI: 5.671
Cites: 72
Cited by: 23
Related to: 9