AUTHOR=Song Yunjia , Wu Siyu , Zhang Rong , Zhong Qing , Zhang Xuanming , Sun Xutao 

TITLE=Therapeutic potential of hydrogen sulfide in osteoarthritis development

JOURNAL=Frontiers in Pharmacology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1336693

DOI=10.3389/fphar.2024.1336693

ISSN=1663-9812

ABSTRACT=<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<sub>2</sub>S) in OA and the therapeutic potential of H<sub>2</sub>S donors. The review highlights the importance of changes in the endogenous H<sub>2</sub>S pathway in OA development and systematically elaborates on the role of H<sub>2</sub>S as a third gaseous transmitter that regulates inflammation, oxidative stress, and pain associated with OA. It also explains how H<sub>2</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-κB) and mitogen-activated protein kinase (MAPK). Additionally, H<sub>2</sub>S is shown to mitigate mitochondrial dysfunction and endoplasmic reticulum stress, and to modulate Nrf2, NF-κB, PI3K/Akt, and MAPK pathways, thereby decreasing oxidative stress-induced chondrocyte apoptosis. Moreover, H<sub>2</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<sub>2</sub>S donors, including sustained-release H<sub>2</sub>S donors, natural H<sub>2</sub>S donors, and synthetic H<sub>2</sub>S donors. Understanding the role of H<sub>2</sub>S in OA can lead to the discovery of new therapeutic targets, while innovative H<sub>2</sub>S donors offer promising new treatments for patients with OA.</p>