Red blood cell exposure increases chondrocyte susceptibility to oxidative stress following hemarthrosis.

Autor: Lee AJ; Department of Biomedical Engineering, Columbia University, 351 Engineering Terrace, Mail Code 8904, 1210 Amsterdam Avenue, New York, NY, USA. Electronic address: jl3924@columbia.edu., Gangi LR; Department of Biomedical Engineering, Columbia University, 351 Engineering Terrace, Mail Code 8904, 1210 Amsterdam Avenue, New York, NY, USA. Electronic address: lrg2147@columbia.edu., Zandkarimi F; Department of Chemistry, Columbia University, 216 Havemeyer Hall, 3000 Broadway, Mail Code 3183, New York, NY, USA. Electronic address: fz2262@columbia.edu., Stockwell BR; Department of Chemistry, Columbia University, 216 Havemeyer Hall, 3000 Broadway, Mail Code 3183, New York, NY, USA; Department of Biological Sciences, Columbia University, 1208 NWC Building, 550 West 120th St. M.C. 4846, New York, NY, USA. Electronic address: bstockwell@columbia.edu., Hung CT; Department of Biomedical Engineering, Columbia University, 351 Engineering Terrace, Mail Code 8904, 1210 Amsterdam Avenue, New York, NY, USA; Department of Orthopaedic Surgery, Columbia University, New York, NY, USA. Electronic address: cth6@columbia.edu.
Jazyk: angličtina
Zdroj: Osteoarthritis and cartilage [Osteoarthritis Cartilage] 2023 Oct; Vol. 31 (10), pp. 1365-1376. Date of Electronic Publication: 2023 Jun 25.
DOI: 10.1016/j.joca.2023.06.007
Abstrakt: Objective: The detrimental effects of blood exposure on articular tissues are well characterized, but the individual contributions of specific whole blood components are yet to be fully elucidated. Better understanding of mechanisms that drive cell and tissue damage in hemophilic arthropathy will inform novel therapeutic strategies. The studies here aimed to identify the specific contributions of intact and lysed red blood cells (RBCs) on cartilage and the therapeutic potential of Ferrostatin-1 in the context of lipid changes, oxidative stress, and ferroptosis.
Methods: Changes to biochemical and mechanical properties following intact RBC treatment were assessed in human chondrocyte-based tissue-engineered cartilage constructs and validated against human cartilage explants. Chondrocyte monolayers were assayed for changes to intracellular lipid profiles and the presence of oxidative and ferroptotic mechanisms.
Results: Markers of tissue breakdown were observed in cartilage constructs without parallel losses in DNA (control: 786.3 (102.2) ng/mg; RBC INT : 751 (126.4) ng/mg; P = 0.6279), implicating nonlethal chondrocyte responses to intact RBCs. Dose-dependent loss of viability in response to intact and lysed RBCs was observed in chondrocyte monolayers, with greater toxicity observed with lysates. Intact RBCs induced changes to chondrocyte lipid profiles, upregulating highly oxidizable fatty acids (e.g., FA 18:2) and matrix disrupting ceramides. RBC lysates induced cell death via oxidative mechanisms that resemble ferroptosis.
Conclusions: Intact RBCs induce intracellular phenotypic changes to chondrocytes that increase vulnerability to tissue damage while lysed RBCs have a more direct influence on chondrocyte death by mechanisms that are representative of ferroptosis.
Competing Interests: Conflict of Interest A.J.L., L.R.G., F.Z., and C.T.H have nothing to disclose. B.R.S. is an inventor on patents and patent applications involving small molecule drug discovery and ferroptosis; has co-founded and serves as a consultant to Inzen Therapeutics, Exarta Therapeutics, and ProJenX, Inc.; serves as a consultant to Weatherwax Biotechnologies Corporation and Akin Gump Strauss Hauer & Feld LLP; and receives sponsored research support from Sumitomo Dainippon Pharma Oncology.
(Copyright © 2023 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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