SARS-CoV-2-induced Overexpression of miR-4485 Suppresses Osteogenic Differentiation and Impairs Fracture Healing

被引：42

作者：

Mi, Bobin ^{[1
]}

Xiong, Yuan ^{[1
]}

Zhang, Chenming ^{[1
]}

Zhou, Wu ^{[1
]}

Chen, Lang ^{[1
]}

Cao, Faqi ^{[1
]}

Chen, Fenghua ^{[2
]}

Geng, Zhi ^{[2
]}

Panayi, Adriana C. ^{[3
]}

Sun, Yun ^{[4
]}

Wang, Lin ^{[2
]}

Liu, Guohui ^{[1
]}

机构：

[1] Huazhong Univ Sci & Technol Wuhan, Union Hosp, Tongji Med Coll, Dept Orthoped, Wuhan 430022, Hubei, Peoples R China

[2] Huazhong Univ Sci & Technol Wuhan, Union Hosp, Tongji Med Coll, Dept Clin Lab, Wuhan 430022, Hubei, Peoples R China

[3] Harvard Med Sch, Brigham & Womens Hosp, Div Plast Surg, Boston, MA 02115 USA

[4] Huazhong Univ Sci & Technol Wuhan, Union Hosp, Tongji Med Coll, Dept Neurosurg, Wuhan 430022, Hubei, Peoples R China

来源：

INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES | 2021年 / 17卷 / 05期

基金：

美国国家科学基金会;

关键词：

INHIBITION; CELLS;

D O I：

10.7150/ijbs.56657

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The angiotensin-converting enzyme 2 (ACE2) receptor has been identified as the cell entry point for SARS-CoV-2. Although ACE2 receptors are present in the bone marrow, the effects of SARS-CoV-2 on the biological activity of bone tissue have not yet been elucidated. In the present study we sought to investigate the impact of SARS-CoV-2 on osteoblastic activity in the context of fracture healing. MicroRNA-4485 (miR-4485), which we found to be upregulated in COVID-19 patients, negatively regulates osteogenic differentiation. We demonstrate this effect both in vitro and in vivo. Moreover, we identified the toll-like receptor 4 (TLR-4) as the potential target gene of miR-4485, and showed that reduction of TLR-4 induced by miR-4485 suppresses osteoblastic differentiation in vitro. Taken together, our findings highlight that up-regulation of miR-4485 is responsible for the suppression of osteogenic differentiation in COVID-19 patients, and TLR-4 is the potential target through which miR-4485 acts, providing a promising target for pro-fracture-healing and anti-osteoporosis therapy in COVID-19 patients.

引用

页码：1277 / 1288

页数：12

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