Blockade of endothelin receptors mitigates SARS-CoV-2-induced osteoarthritis

Au, Man Ting1; Ni, Junguo1; Tang, Kaiming2; Wang, Wei1; Zhang, Lanlan1; Wang, Hantang1; Zhao, Fangyi1; Li, Zhan1; Luo, Peng2; Lau, Lawrence Chun-Man3; Chan, Ping-Keung3; Luo, Cuiting2; Zhou, Bo4; Zhu, Lin5; Zhang, Charlie Yuli1; Jiang, Tianshu1; Lauwers, Marianne1; Chan, Jasper Fuk-Woo2,6,7; Yuan, Shuofeng2,6,7; Wen, Chunyi1,8

2024-09-01

10.1038/s41564-024-01802-x

NATURE MICROBIOLOGY   影响因子和分区

2058-5276

["Joint pain and osteoarthritis can occur as coronavirus disease 2019 (COVID-19) sequelae after infection. However, little is known about the damage to articular cartilage. Here we illustrate knee joint damage after wild-type, Delta and Omicron variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in vivo. Rapid joint injury with cystic lesions at the osteochondral junction was observed in two patients with post-COVID osteoarthritis and recapitulated in a golden Syrian hamster model. SARS-CoV-2-activated endothelin-1 signalling increased vascular permeability and caused viral spike proteins leakage into the subchondral bone. Osteoclast activation, chondrocyte dropout and cyst formation were confirmed histologically. The US Food and Drug Administration-approved endothelin receptor antagonist, macitentan, mitigated cystic lesions and preserved chondrocyte number in the acute phase of viral infection in hamsters. Delayed macitentan treatment at post-acute infection phase alleviated chondrocyte senescence and restored subchondral bone loss. It is worth noting that it could also attenuate viral spike-induced joint pain. Our work suggests endothelin receptor blockade as a novel therapeutic strategy for post-COVID arthritis.","Endothelin-1 activation after SARS-CoV-2 infection leads to vascular permeability, chondrocyte senescence, osteoclast activation and cyst formation in affected joints of hamsters, which can be alleviated using macitentan. Joint injury was also seen in two patients after COVID-19 infection."]

SCI

英语

其他

Food and Health Bureau of the Government of the Hong Kong Special Administrative Region | Health and Medical Research Fund (HMRF)["16172691","07210107"] ; Food and Health Bureau, The Government of the Hong Kong Special Administrative Region["151061/20M","PolyU15100821M","15100324","C7060-21G","T11-709/21-N"] ; National Natural Science Foundation of China (NSFC)["N_PolyU 520/20","N_HKU767/22","MHP/011/20"] ; Innovation and Technology Commission["2021YFC0866100","2023YFC3041600","32322087","32300134"] ; National Key Research and Development Program of China[I2022A006]

Microbiology

Microbiology

WOS:001310046300001

NATURE PORTFOLIO

Web of Science

1.Hong Kong Polytech Univ, Dept Biomed Engn, Hong Kong, Peoples R China
2.Univ Hong Kong, Li Ka Shing Fac Med, Sch Clin Med, Dept Microbiol,State Key Lab Emerging Infect Dis, Hong Kong, Peoples R China
3.Univ Hong Kong, Li Ka Shing Fac Med, Sch Clin Med, Dept Orthopaed & Traumatol, Hong Kong, Peoples R China
4.Southern Univ Sci & Technol, Dept Biochem, Sch Med, Shenzhen, Peoples R China
5.Hong Kong Baptist Univ, State Key Lab Environm & Biol Anal, Hong Kong, Peoples R China
6.Univ Hong Kong, Shenzhen Hosp, Dept Infect Dis & Microbiol, Shenzhen, Peoples R China
7.Ctr Virol Vaccinol & Therapeut, Hong Kong Sci & Technol Pk, Hong Kong, Peoples R China
8.Hong Kong Polytech Univ, Res Inst Smart Ageing, Hong Kong, Peoples R China

Au, Man Ting,Ni, Junguo,Tang, Kaiming,et al. Blockade of endothelin receptors mitigates SARS-CoV-2-induced osteoarthritis[J]. NATURE MICROBIOLOGY,2024.

Au, Man Ting.,Ni, Junguo.,Tang, Kaiming.,Wang, Wei.,Zhang, Lanlan.,...&Wen, Chunyi.(2024).Blockade of endothelin receptors mitigates SARS-CoV-2-induced osteoarthritis.NATURE MICROBIOLOGY.

Au, Man Ting,et al."Blockade of endothelin receptors mitigates SARS-CoV-2-induced osteoarthritis".NATURE MICROBIOLOGY (2024).