Elevated Lipid Metabolites in Stored Clinical OCA Media Correlate With Chondrocyte Death.

Autor:	Tabbaa SM; University of California, San Francisco, San Francisco, California, USA., Guilak F; Washington University, St. Louis, Missouri, USA.; Shriners Hospitals for Children, St. Louis, Missouri, USA., Lemmerman LR; The Ohio State University, Columbus, Ohio, USA., Glembotski N; Scripps Clinic, La Jolla, California, USA., D'Lima DD; Scripps Clinic, La Jolla, California, USA., Wang T; University of Tennessee, Knoxville, Tennessee, USA., Bugbee WD; The Ohio State University, Columbus, Ohio, USA.
Jazyk:	angličtina
Zdroj:	The American journal of sports medicine [Am J Sports Med] 2024 Jul; Vol. 52 (8), pp. 2119-2128. Date of Electronic Publication: 2024 Jun 10.
DOI:	10.1177/03635465241252653
Abstrakt:	Background: A major limitation of osteochondral allografts (OCA) is the deterioration of cartilage health associated with cell death during prolonged storage. However, little is known about the mechanisms that contribute to chondrocyte death during storage. Purpose/hypothesis: This study aimed to determine whether bioactive lipid metabolites accumulate in the storage media of OCA and whether they are associated with a loss of chondrocyte viability during prolonged storage. It was hypothesized that free fatty acids (FFAs) would accumulate over time in the storage media of OCA and adversely affect cartilage health during storage. Study Design: Controlled laboratory study. Methods: A group of 21 (n = 6-8 OCA/treatment group) fresh human hemicondylar OCA tissues and media were analyzed after 7, 28, and 68 days of prolonged cold (4°C) storage. Targeted mass spectrometry analysis was used to quantify bioactive FFAs, as well as primary (lipid hydroperoxide [ROOH]) and secondary (malondialdehyde) lipid oxidation products. Chondrocyte viability was measured using a fluorescence-based live/dead assay and confocal microscopy. Results: The concentration of all targeted fatty acid metabolites in storage media was significantly increased with increased cold storage time ( P < .05). ROOH was significantly higher on day 28 of cold storage. No difference in secondary ROOH products in storage media was observed. Chondrocyte viability significantly declined in both the en face and the vertical cross-sectional analysis with increased cold storage time and inversely correlated with fatty acid metabolites ( P < .05). Conclusion: It is well established that elevated levels of certain FFAs and lipid oxidation products can alter cell function and cause cell death via lipotoxicity and other mechanisms. This work is the first to identify elevated levels of FFA metabolites and primary oxidation lipid products in the storage media from clinical OCA. The concentrations of FFA metabolites were measured at levels (>100 µM) known to induce cell death and were directly correlated with chondrocyte viability. Clinical Relevance: These findings provide important targets for understanding why cartilage health declines during cold storage, which can be used to optimize media formulations and improve graft health. Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: S.M.T. has received consulting fees from JRF Ortho and is a member of Restoration Biologics LLC. F.G. is a shareholder and employee of Cytex Therapeutics Inc and is a member of Restoration Biologics LLC. L.R.L. has received consulting fees from Restoration Biologics LLC. N.G. has received research support from Restoration Biologics LLC for this project. D.D. has received research support from Restoration Biologics LLC for this project. W.D.B. has received consulting fees from JRF Ortho, Arthrex, Depuy Synthes, Insight Medical, OrthAlign, Smith & Nephew, Medical Device Business Services, and Bioventus; research support from Depuy Synthes; and royalties from DePuy, Smith & Nephew, Zimmer Biomet, and Encore Medical and is a member of Restoration Biologics LLC; he holds stock or stock options from Insight Medical and Orthalign. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.
Databáze:	MEDLINE
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