Therapeutic potential of hydrogen sulfide in osteoarthritis development.

The pathological mechanisms and treatments of osteoarthritis (OA) are critical topics in medical research. This paper reviews the regulatory mechanisms of hydrogen sulfide (HS) in OA and the therapeutic potential of HS donors. The review highlights the importance of changes in the endogenous HS pathway in OA development and systematically elaborates on the role of HS as a third gaseous transmitter that regulates inflammation, oxidative stress, and pain associated with OA. It also explains how HS 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, HS 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, HS 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 HS donors, including sustained-release HS donors, natural HS donors, and synthetic HS donors. Understanding the role of HS in OA can lead to the discovery of new therapeutic targets, while innovative HS donors offer promising new treatments for patients with OA.