Natalia Lendoiro-Cino, Arianna Rodríguez-Coello, Anna Saborido, Elena F-Burguera, Jennifer A Fernández-Rodríguez, Rosa Meijide-Faílde, Francisco J Blanco, Carlos Vaamonde-García
{"title":"糖尿病相关性骨关节炎滑膜组织硫化氢生物合成及其对巨噬细胞表型和丰度影响的研究。","authors":"Natalia Lendoiro-Cino, Arianna Rodríguez-Coello, Anna Saborido, Elena F-Burguera, Jennifer A Fernández-Rodríguez, Rosa Meijide-Faílde, Francisco J Blanco, Carlos Vaamonde-García","doi":"10.1007/s13105-023-00968-y","DOIUrl":null,"url":null,"abstract":"<p><p>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<sub>2</sub>S) has been previously described to be involved in macrophage polarization, in this study we examined H<sub>2</sub>S biosynthesis in synovial tissue from OA patients with DB, observing a reduction of H<sub>2</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<sub>2</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<sub>2</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-1α expression and upregulated the protein levels of HO-1, suggesting their involvement in the anti-inflammatory effects of H<sub>2</sub>S induction. In addition, we observed that intraarticular administration of H<sub>2</sub>S donor attenuated synovial abundance of CD68<sup>+</sup> 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<sub>2</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.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":null,"pages":null},"PeriodicalIF":3.7000,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10338594/pdf/","citationCount":"0","resultStr":"{\"title\":\"Study of hydrogen sulfide biosynthesis in synovial tissue from diabetes-associated osteoarthritis and its influence on macrophage phenotype and abundance.\",\"authors\":\"Natalia Lendoiro-Cino, Arianna Rodríguez-Coello, Anna Saborido, Elena F-Burguera, Jennifer A Fernández-Rodríguez, Rosa Meijide-Faílde, Francisco J Blanco, Carlos Vaamonde-García\",\"doi\":\"10.1007/s13105-023-00968-y\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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<sub>2</sub>S) has been previously described to be involved in macrophage polarization, in this study we examined H<sub>2</sub>S biosynthesis in synovial tissue from OA patients with DB, observing a reduction of H<sub>2</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<sub>2</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<sub>2</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-1α expression and upregulated the protein levels of HO-1, suggesting their involvement in the anti-inflammatory effects of H<sub>2</sub>S induction. In addition, we observed that intraarticular administration of H<sub>2</sub>S donor attenuated synovial abundance of CD68<sup>+</sup> 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<sub>2</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.</p>\",\"PeriodicalId\":16779,\"journal\":{\"name\":\"Journal of physiology and biochemistry\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2023-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10338594/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of physiology and biochemistry\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1007/s13105-023-00968-y\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of physiology and biochemistry","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1007/s13105-023-00968-y","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Study of hydrogen sulfide biosynthesis in synovial tissue from diabetes-associated osteoarthritis and its influence on macrophage phenotype and abundance.
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 (H2S) has been previously described to be involved in macrophage polarization, in this study we examined H2S biosynthesis in synovial tissue from OA patients with DB, observing a reduction of H2S-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 H2S-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 H2S 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 H2S induction. In addition, we observed that intraarticular administration of H2S 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 H2S 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.
期刊介绍:
The Journal of Physiology and Biochemistry publishes original research articles and reviews describing relevant new observations on molecular, biochemical and cellular mechanisms involved in human physiology. All areas of the physiology are covered. Special emphasis is placed on the integration of those levels in the whole-organism. The Journal of Physiology and Biochemistry also welcomes articles on molecular nutrition and metabolism studies, and works related to the genomic or proteomic bases of the physiological functions. Descriptive manuscripts about physiological/biochemical processes or clinical manuscripts will not be considered. The journal will not accept manuscripts testing effects of animal or plant extracts.