AnnexinA6: a potential therapeutic target gene for extracellular matrix mineralization

Jie Yang; Tong Pei; Guanyue Su; Peiyan Duan; Xiaoheng Liu

doi:10.3389/fcell.2023.1201200

AnnexinA6: a potential therapeutic target gene for extracellular matrix mineralization

Front Cell Dev Biol. 2023 Sep 4:11:1201200. doi: 10.3389/fcell.2023.1201200. eCollection 2023.

Authors

Jie Yang^#¹, Tong Pei^#¹, Guanyue Su¹, Peiyan Duan¹, Xiaoheng Liu¹

Affiliation

¹ Institute of Biomedical Engineering, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, China.

^# Contributed equally.

Abstract

The mineralization of the extracellular matrix (ECM) is an essential and crucial process for physiological bone formation and pathological calcification. The abnormal function of ECM mineralization contributes to the worldwide risk of developing mineralization-related diseases; for instance, vascular calcification is attributed to the hyperfunction of ECM mineralization, while osteoporosis is due to hypofunction. AnnexinA6 (AnxA6), a Ca²⁺-dependent phospholipid-binding protein, has been extensively reported as an essential target in mineralization-related diseases such as osteoporosis, osteoarthritis, atherosclerosis, osteosarcoma, and calcific aortic valve disease. To date, AnxA6, as the largest member of the Annexin family, has attracted much attention due to its significant contribution to matrix vesicles (MVs) production and release, MVs-ECM interaction, cytoplasmic Ca²⁺ influx, and maturation of hydroxyapatite, making it an essential target in ECM mineralization. In this review, we outlined the recent advancements in the role of AnxA6 in mineralization-related diseases and the potential mechanisms of AnxA6 under normal and mineralization-related pathological conditions. AnxA6 could promote ECM mineralization for bone regeneration in the manner described previously. Therefore, AnxA6 may be a potential osteogenic target for ECM mineralization.

Keywords: AnnexinA6; Ca2+ regulation; bone regeneration; extracellular matrix mineralization; matrix vesicles; osteogenesis.

Publication types

Review

Grants and funding

This study was supported by the National Natural Science Foundation of China (Nos 11932014 and 31971239) and Sichuan Science and Technology Program (Nos 2022NSFSC0765 and 2022ZYD0079).