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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<jats:sub>2<\/jats:sub>S) has been previously described to be involved in macrophage polarization, in this study we examined H<jats:sub>2<\/jats:sub>S biosynthesis in synovial tissue from OA patients with DB, observing a reduction of H<jats:sub>2<\/jats:sub>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<jats:sub>2<\/jats:sub>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<jats:sub>2<\/jats:sub>S donor, GYY-4137, attenuated the expression of M1 markers, but failed to modulate the levels of M2 indicators. GYY-4137 also reduced HIF-1\u03b1 expression and upregulated the protein levels of HO-1, suggesting their involvement in the anti-inflammatory effects of H<jats:sub>2<\/jats:sub>S induction. In addition, we observed that intraarticular administration of H<jats:sub>2<\/jats:sub>S donor attenuated synovial abundance of CD68<jats:sup>+<\/jats:sup> cells, mainly macrophages, in an <jats:italic>in vivo<\/jats:italic> model of OA. Taken together, the findings of this study seem to reinforce the key role of H<jats:sub>2<\/jats:sub>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.<\/jats:p>","DOI":"10.1007\/s13105-023-00968-y","type":"journal-article","created":{"date-parts":[[2023,6,19]],"date-time":"2023-06-19T08:02:41Z","timestamp":1687161761000},"page":"653-667","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Study of hydrogen sulfide biosynthesis in synovial tissue from diabetes-associated osteoarthritis and its influence on macrophage phenotype and abundance"],"prefix":"10.1007","volume":"79","author":[{"given":"Natalia","family":"Lendoiro-Cino","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arianna","family":"Rodr\u00edguez-Coello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Saborido","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"F-Burguera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer A.","family":"Fern\u00e1ndez-Rodr\u00edguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Meijide-Fa\u00edlde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco J.","family":"Blanco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8658-5502","authenticated-orcid":false,"given":"Carlos","family":"Vaamonde-Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,6,19]]},"reference":[{"key":"968_CR1","doi-asserted-by":"publisher","first-page":"2500","DOI":"10.3390\/cells11162500","volume":"11","author":"M Adel","year":"2022","unstructured":"Adel M, Elsayed HRH, El-Nablaway M, Hamed S, Eladl A, Fouad S, El Nashar EM, Al-Otaibi ML, Rabei MR (2022) Targeting hydrogen sulfide modulates dexamethasone-induced muscle atrophy and microvascular rarefaction, through inhibition of NOX4 and induction of MGF, M2 macrophages and endothelial progenitors. 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