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Pharmacol."],"abstract":"<jats:p>The pathological mechanisms and treatments of osteoarthritis (OA) are critical topics in medical research. This paper reviews the regulatory mechanisms of hydrogen sulfide (H<jats:sub>2<\/jats:sub>S) in OA and the therapeutic potential of H<jats:sub>2<\/jats:sub>S donors. The review highlights the importance of changes in the endogenous H<jats:sub>2<\/jats:sub>S pathway in OA development and systematically elaborates on the role of H<jats:sub>2<\/jats:sub>S as a third gaseous transmitter that regulates inflammation, oxidative stress, and pain associated with OA. It also explains how H<jats:sub>2<\/jats:sub>S can lessen bone and joint inflammation by inhibiting leukocyte adhesion and migration, reducing pro-inflammatory mediators, and impeding the activation of key inflammatory pathways such as nuclear factor kappa B (NF-\u03baB) and mitogen-activated protein kinase (MAPK). Additionally, H<jats:sub>2<\/jats:sub>S is shown to mitigate mitochondrial dysfunction and endoplasmic reticulum stress, and to modulate Nrf2, NF-\u03baB, PI3K\/Akt, and MAPK pathways, thereby decreasing oxidative stress-induced chondrocyte apoptosis. Moreover, H<jats:sub>2<\/jats:sub>S alleviates bone and joint pain through the activation of Kv7, K-ATP, and Nrf2\/HO-1-NQO1 pathways. Recent developments have produced a variety of H<jats:sub>2<\/jats:sub>S donors, including sustained-release H<jats:sub>2<\/jats:sub>S donors, natural H<jats:sub>2<\/jats:sub>S donors, and synthetic H<jats:sub>2<\/jats:sub>S donors. Understanding the role of H<jats:sub>2<\/jats:sub>S in OA can lead to the discovery of new therapeutic targets, while innovative H<jats:sub>2<\/jats:sub>S donors offer promising new treatments for patients with OA.<\/jats:p>","DOI":"10.3389\/fphar.2024.1336693","type":"journal-article","created":{"date-parts":[[2024,2,2]],"date-time":"2024-02-02T04:16:27Z","timestamp":1706847387000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Therapeutic potential of hydrogen sulfide in osteoarthritis development"],"prefix":"10.3389","volume":"15","author":[{"given":"Yunjia","family":"Song","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyu","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuanming","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xutao","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,2,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1016\/j.mcna.2019.10.007","article-title":"Osteoarthritis: pathology, diagnosis, and treatment options","volume":"104","author":"Abramoff","year":"2020","journal-title":"Med. 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