Osteoarthritis-Induced Metabolic Alterations of Human Hip Chondrocytes

GND
129357898
ORCID
0000-0002-0590-3001
Affiliation
Department of Trauma, Hand and Reconstructive Surgery, Experimental Trauma Surgery, Jena University Hospital, Friedrich-Schiller-University Jena, 07747 Jena, Germany;(S.S.);(F.C.K.);(G.O.H.)
Eitner, Annett;
Affiliation
Department of Trauma, Hand and Reconstructive Surgery, Experimental Trauma Surgery, Jena University Hospital, Friedrich-Schiller-University Jena, 07747 Jena, Germany;(S.S.);(F.C.K.);(G.O.H.)
Sparing, Simon;
ORCID
0000-0002-6863-9025
Affiliation
Department of Trauma, Hand and Reconstructive Surgery, Experimental Trauma Surgery, Jena University Hospital, Friedrich-Schiller-University Jena, 07747 Jena, Germany;(S.S.);(F.C.K.);(G.O.H.)
Kohler, Felix C.;
Affiliation
Institute of Immunology, Jena University Hospital, Friedrich-Schiller-University Jena, 07743 Jena, Germany;(S.M.);(T.K.)
Müller, Sylvia;
GND
110673522
Affiliation
Department of Trauma, Hand and Reconstructive Surgery, Experimental Trauma Surgery, Jena University Hospital, Friedrich-Schiller-University Jena, 07747 Jena, Germany;(S.S.);(F.C.K.);(G.O.H.)
Hofmann, Gunther O.;
GND
123172292
Affiliation
Institute of Immunology, Jena University Hospital, Friedrich-Schiller-University Jena, 07743 Jena, Germany;(S.M.);(T.K.)
Kamradt, Thomas;
GND
1093853360
Affiliation
Institute of Physiology 1/Neurophysiology, Jena University Hospital, Friedrich-Schiller-University Jena, 07743 Jena, Germany;
Schaible, Hans-Georg;
ORCID
0000-0002-9039-1687
Affiliation
BG Trauma Center Bergmannstrost, 06112 Halle (Saale), Germany;
Aurich, Matthias

Osteoarthritis (OA) alters chondrocyte metabolism and mitochondrial biology. We explored whether OA and non-OA chondrocytes show persistent differences in metabolism and mitochondrial function and different responsiveness to cytokines and cAMP modulators. Hip chondrocytes from patients with OA or femoral neck fracture (non-OA) were stimulated with IL-1β, TNF, forskolin and opioid peptides. Mediators released from chondrocytes were measured, and mitochondrial functions and glycolysis were determined (Seahorse Analyzer). Unstimulated OA chondrocytes exhibited significantly higher release of IL-6, PGE 2 and MMP1 and lower production of glycosaminoglycan than non-OA chondrocytes. Oxygen consumption rates (OCR) and mitochondrial ATP production were comparable in unstimulated non-OA and OA chondrocytes, although the non-mitochondrial OCR was higher in OA chondrocytes. Compared to OA chondrocytes, non-OA chondrocytes showed stronger responses to IL-1β/TNF stimulation, consisting of a larger decrease in mitochondrial ATP production and larger increases in non-mitochondrial OCR and NO production. Enhancement of cAMP by forskolin prevented IL-1β-induced mitochondrial dysfunction in OA chondrocytes but not in non-OA chondrocytes. Endogenous opioids, present in OA joints, influenced neither cytokine-induced mitochondrial dysfunction nor NO upregulation. Glycolysis was not different in non-OA and OA chondrocytes, independent of stimulation. OA induces persistent metabolic alterations, but the results suggest upregulation of cellular mechanisms protecting mitochondrial function in OA.

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