Carbon Monoxide Stimulates Chondrocyte Mitochondria and Protects Mitochondria During Cartilage Injury
Year: 2025
Type: article
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.
Source: Antioxidants
Institutions: University of Iowa, University of North Carolina Wilmington
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,499
Funders: National Science Foundation, U.S. Department of Defense, American Cancer Society, V Foundation for Cancer Research, National Institutes of Health, Holden Comprehensive Cancer Center, University of Iowa, National Cancer Institute, National Institute of Arthritis and Musculoskeletal and Skin Diseases
Awards: G1045139486, G1700165370, G3780238105, G4119534169, G43984215, G5289693159, G5381295387, G5739943101, Collaborative Research: Role of endogenous carbon monoxide (CO) in hypoxia tolerant species, TRANSLATING METABOLIC RESPONSES TO MECHANICAL INSULT INTO EARLY INTERVENTIONS TO PREVENT PTOA, G630064964, G6469831421, MITOCHONDRIAL-BASED TREATMENTS THAT PREVENT POST-TRAUMATIC OSTEOARTHRITIS IN A TRANSLATIONAL LARGE ANIMAL INTRAARTICULAR FRACTURE SURVIVAL MODEL, G6789205356, G6947463281, G6984237608, G7011019624, Preclinical models of serous endometrial cancer from diverse patient populations, G765467158, G8166743225, G8299222776, G8368690009, G9000018865, G9000055956, G9000238641
OpenAlex ID: W4409814152