tetano
Editor, Senior Moderator
Nat Microbiol
. 2024 Sep 11.
doi: 10.1038/s41564-024-01802-x. Online ahead of print. Blockade of endothelin receptors mitigates SARS-CoV-2-induced osteoarthritis
Man Ting Au[SUP] #[/SUP][SUP] 1 [/SUP], Junguo Ni[SUP] #[/SUP][SUP] 1 [/SUP], Kaiming Tang[SUP] #[/SUP][SUP] 2 [/SUP], Wei Wang[SUP] 1 [/SUP], Lanlan Zhang[SUP] 1 [/SUP], Hantang Wang[SUP] 1 [/SUP], Fangyi Zhao[SUP] 1 [/SUP], Zhan Li[SUP] 1 [/SUP], Peng Luo[SUP] 2 [/SUP], Lawrence Chun-Man Lau[SUP] 3 [/SUP], Ping-Keung Chan[SUP] 3 [/SUP], Cuiting Luo[SUP] 2 [/SUP], Bo Zhou[SUP] 4 [/SUP], Lin Zhu[SUP] 5 [/SUP], Charlie Yuli Zhang[SUP] 1 [/SUP], Tianshu Jiang[SUP] 1 [/SUP], Marianne Lauwers[SUP] 1 [/SUP], Jasper Fuk-Woo Chan[SUP] 2 6 7 [/SUP], Shuofeng Yuan[SUP] 8 9 10 [/SUP], Chunyi Wen[SUP] 11 12 [/SUP]
Affiliations
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.
. 2024 Sep 11.
doi: 10.1038/s41564-024-01802-x. Online ahead of print. Blockade of endothelin receptors mitigates SARS-CoV-2-induced osteoarthritis
Man Ting Au[SUP] #[/SUP][SUP] 1 [/SUP], Junguo Ni[SUP] #[/SUP][SUP] 1 [/SUP], Kaiming Tang[SUP] #[/SUP][SUP] 2 [/SUP], Wei Wang[SUP] 1 [/SUP], Lanlan Zhang[SUP] 1 [/SUP], Hantang Wang[SUP] 1 [/SUP], Fangyi Zhao[SUP] 1 [/SUP], Zhan Li[SUP] 1 [/SUP], Peng Luo[SUP] 2 [/SUP], Lawrence Chun-Man Lau[SUP] 3 [/SUP], Ping-Keung Chan[SUP] 3 [/SUP], Cuiting Luo[SUP] 2 [/SUP], Bo Zhou[SUP] 4 [/SUP], Lin Zhu[SUP] 5 [/SUP], Charlie Yuli Zhang[SUP] 1 [/SUP], Tianshu Jiang[SUP] 1 [/SUP], Marianne Lauwers[SUP] 1 [/SUP], Jasper Fuk-Woo Chan[SUP] 2 6 7 [/SUP], Shuofeng Yuan[SUP] 8 9 10 [/SUP], Chunyi Wen[SUP] 11 12 [/SUP]
Affiliations
- PMID: 39261580
- DOI: 10.1038/s41564-024-01802-x
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.