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Carbon Monoxide Stimulates Chondrocyte Mitochondria and Protects Mitochondria During Cartilage Injury
Journal article   Open access   Peer reviewed

Carbon Monoxide Stimulates Chondrocyte Mitochondria and Protects Mitochondria During Cartilage Injury

Suryamin Liman, Madeline R. Hines, Piedad C. Gómez-Contreras, Emily Witt, Jacob S. Fisher, Kevin J. Lu, Lauren D. McNally, Alicia T. Cotoia, Maxwell Y. Sakyi, Brett A. Wagner, …
Antioxidants, Vol.14(5), 514
04/25/2025
DOI: 10.3390/antiox14050514
PMCID: PMC12108337
PMID: 40427396
url
https://doi.org/10.3390/antiox14050514View
Published (Version of record) Open Access

Abstract

Objective: Joint injury precipitates post-traumatic osteoarthritis (PTOA) via chondrocyte mitochondrial oxidative damage. Carbon monoxide (CO) is a small molecule with potent antioxidant and mitochondrial benefits in other tissues that have not been explored in healthy chondrocytes. We hypothesized that CO would subvert the mitochondrial effects of articular cartilage injuries upon resident chondrocytes. Design: We evaluated intra-articular delivery of a novel carbon monoxide-containing foam (COF). We used in vitro impact injuries to explore mitochondrial and redox endpoints after CO exposure. We then applied intra-articular injections of COF or control room air foam (RAF) to assess safety, efficacy, and other intra-articular responses. Results: COF increased the expression of HO1 and mitofusin-1 within 1 h and this increase was sustained for 12 h in vitro. COF increased chondrocyte mitochondrial respiration by 40% and increased reduced (not oxidized) thiols by 50% following in vitro injury to osteochondral explants. After cartilage injury, COF prevented the formation of 3-nitrotyrosine and the loss of articular chondrocyte mitochondria. When injected intra-articularly, COF was retained for 24 h post-injection in mouse stifle joints. It increased HO1 in those joints, enhanced reduced thiol levels in rabbit stifle joints, and exhibited no toxicity 1 and 4 weeks after injection. Conclusions: This study supports the hypothesis that CO functions as an antioxidant for articular chondrocytes by supporting mitochondria and intracellular GSH in the presence or absence of cartilage injury. Challenges in delivering exogenous CO have limited its preclinical development, but new CO-releasing materials like COF may enable new examinations of this promising small molecule.
 cartilage carbon monoxide mitochondria glutathione monochlorobimane

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