Study of hydrogen sulfide biosynthesis in synovial tissue from diabetes-associated osteoarthritis and its influence on macrophage phenotype and abundance

• Published in: Journal of physiology and biochemistry 2023-08, Vol.79 (3), p.653-667
• Main Authors: Lendoiro-Cino, Natalia, Rodríguez-Coello, Arianna, Saborido, Anna, F-Burguera, Elena, Fernández-Rodríguez, Jennifer A., Meijide-Faílde, Rosa, Blanco, Francisco J., Vaamonde-García, Carlos
• Format: Article
• Language: English
• Subjects: Analysis; Animal Physiology; Arthritis; Biomedical and Life Sciences; Biomedicine; Biosynthesis; CD11c antigen; CD163 antigen; CD86 antigen; Cell differentiation; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - metabolism; Enzymes; Ethylenediaminetetraacetic acid; Genetic aspects; Genotype & phenotype; Human Physiology; Humans; Hydrogen sulfide; Hydrogen Sulfide - metabolism; Hydrogen Sulfide - pharmacology; Hypoxia-inducible factor 1a; In vivo methods and tests; Inflammation; Inflammatory response; Interleukin 6; Macrophages; Macrophages - metabolism; Nitric-oxide synthase; Original; Original Article; Osteoarthritis; Osteoarthritis - metabolism; Phenotype; Phenotypes; Polarization; Risk factors; Type 2 diabetes
• ISSN: 1138-7548; 1877-8755
• DOI: 10.1007/s13105-023-00968-y

Type 2 diabetes (DB) is an independent risk factor for osteoarthritis (OA). However, the mechanisms underlying the connection between both diseases remain unclear. Synovial macrophages from OA patients with DB present a marked pro-inflammatory phenotype. Since hydrogen sulphide (H 2 S) has been previously described to be involved in macrophage polarization, in this study we examined H 2 S biosynthesis in synovial tissue from OA patients with DB, observing a reduction of H 2 S-synthetizing enzymes in this subset of individuals. To elucidate these findings, we detected that differentiated TPH-1 cells to macrophages exposed to high levels of glucose presented a lower expression of H 2 S-synthetizing enzymes and an increased inflammatory response to LPS, showing upregulated expression of markers associated with M1 phenotype (i.e., CD11c, CD86, iNOS, and IL-6) and reduced levels of those related to M2 fate (CD206 and CD163). The co-treatment of the cells with a slow-releasing H 2 S donor, GYY-4137, attenuated the expression of M1 markers, but failed to modulate the levels of M2 indicators. GYY-4137 also reduced HIF-1α expression and upregulated the protein levels of HO-1, suggesting their involvement in the anti-inflammatory effects of H 2 S induction. In addition, we observed that intraarticular administration of H 2 S donor attenuated synovial abundance of CD68 + cells, mainly macrophages, in an in vivo model of OA. Taken together, the findings of this study seem to reinforce the key role of H 2 S in the M1-like polarization of synovial macrophages associated to OA and specifically its metabolic phenotype, opening new therapeutic perspectives in the management of this pathology.