{"title":"METTL3抑制剂通过靶向MyD88减轻小鼠骨髓炎的发作","authors":"Chuan-Yu Hu, Yong Jiao","doi":"10.7883/yoken.JJID.2022.454","DOIUrl":null,"url":null,"abstract":"<p><p>We aimed to study the effects of a methyltransferase 3 (METTL3) inhibitor on osteomyelitis. Bone marrow cells (BMs) and peripheral blood mononuclear cells (PBMCs) were isolated from osteomyelitis patients at our hospital. Primary BM-derived macrophages (BMDMs) were incubated with lipopolysaccharide (LPS), poly(I:C), or PAM3CSK4 after pretreatment with STM2457. S. aureus was injected into the intramedullary canal to construct an osteomyelitis C57BL/6 mice model, which was then treated with STM2457. Body weights, μCT three-dimensional analyses, and bacterial burdens of the mice were obtained. Up-regulated METTL3 expression was found in both BMs and PBMCs of osteomyelitis patients. LPS and PAM3CSK4-induced IL-6 and TNF-α secretion in BMDMs could be inhibited by STM2457 pretreatment, while STM2457 pretreatment did not affect the relative expression of NOS2, IL-6, and TNF-α after incubation with poly(I:C). STM2457 alleviated the symptoms of osteomyelitis in mice with increased body weights, diminished reactive bone formation and cortical bone loss, increased bacterial burdens, and decreased IL-6 and TNF-α secretion. STM2457 pretreatment down-regulated the relative expression of myeloid differentiation factor 88 (MyD88), p-TAK, and p-IKKα/β in LPS-stimulated BMDMs, while it did not show any effect on poly(I:C)-stimulated BMDMs. STM2457 alleviates the onset of osteomyelitis in mice by down-regulating the relative expression of MyD88 and NF-κB relevant inflammation molecules in macrophages.</p>","PeriodicalId":14608,"journal":{"name":"Japanese journal of infectious diseases","volume":null,"pages":null},"PeriodicalIF":1.3000,"publicationDate":"2023-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A METTL3 Inhibitor Alleviates the Onset of Osteomyelitis in a Mouse Model by Targeting MyD88.\",\"authors\":\"Chuan-Yu Hu, Yong Jiao\",\"doi\":\"10.7883/yoken.JJID.2022.454\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>We aimed to study the effects of a methyltransferase 3 (METTL3) inhibitor on osteomyelitis. Bone marrow cells (BMs) and peripheral blood mononuclear cells (PBMCs) were isolated from osteomyelitis patients at our hospital. Primary BM-derived macrophages (BMDMs) were incubated with lipopolysaccharide (LPS), poly(I:C), or PAM3CSK4 after pretreatment with STM2457. S. aureus was injected into the intramedullary canal to construct an osteomyelitis C57BL/6 mice model, which was then treated with STM2457. Body weights, μCT three-dimensional analyses, and bacterial burdens of the mice were obtained. Up-regulated METTL3 expression was found in both BMs and PBMCs of osteomyelitis patients. LPS and PAM3CSK4-induced IL-6 and TNF-α secretion in BMDMs could be inhibited by STM2457 pretreatment, while STM2457 pretreatment did not affect the relative expression of NOS2, IL-6, and TNF-α after incubation with poly(I:C). STM2457 alleviated the symptoms of osteomyelitis in mice with increased body weights, diminished reactive bone formation and cortical bone loss, increased bacterial burdens, and decreased IL-6 and TNF-α secretion. STM2457 pretreatment down-regulated the relative expression of myeloid differentiation factor 88 (MyD88), p-TAK, and p-IKKα/β in LPS-stimulated BMDMs, while it did not show any effect on poly(I:C)-stimulated BMDMs. STM2457 alleviates the onset of osteomyelitis in mice by down-regulating the relative expression of MyD88 and NF-κB relevant inflammation molecules in macrophages.</p>\",\"PeriodicalId\":14608,\"journal\":{\"name\":\"Japanese journal of infectious diseases\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.3000,\"publicationDate\":\"2023-05-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Japanese journal of infectious diseases\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.7883/yoken.JJID.2022.454\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"INFECTIOUS DISEASES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Japanese journal of infectious diseases","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.7883/yoken.JJID.2022.454","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}
A METTL3 Inhibitor Alleviates the Onset of Osteomyelitis in a Mouse Model by Targeting MyD88.
We aimed to study the effects of a methyltransferase 3 (METTL3) inhibitor on osteomyelitis. Bone marrow cells (BMs) and peripheral blood mononuclear cells (PBMCs) were isolated from osteomyelitis patients at our hospital. Primary BM-derived macrophages (BMDMs) were incubated with lipopolysaccharide (LPS), poly(I:C), or PAM3CSK4 after pretreatment with STM2457. S. aureus was injected into the intramedullary canal to construct an osteomyelitis C57BL/6 mice model, which was then treated with STM2457. Body weights, μCT three-dimensional analyses, and bacterial burdens of the mice were obtained. Up-regulated METTL3 expression was found in both BMs and PBMCs of osteomyelitis patients. LPS and PAM3CSK4-induced IL-6 and TNF-α secretion in BMDMs could be inhibited by STM2457 pretreatment, while STM2457 pretreatment did not affect the relative expression of NOS2, IL-6, and TNF-α after incubation with poly(I:C). STM2457 alleviated the symptoms of osteomyelitis in mice with increased body weights, diminished reactive bone formation and cortical bone loss, increased bacterial burdens, and decreased IL-6 and TNF-α secretion. STM2457 pretreatment down-regulated the relative expression of myeloid differentiation factor 88 (MyD88), p-TAK, and p-IKKα/β in LPS-stimulated BMDMs, while it did not show any effect on poly(I:C)-stimulated BMDMs. STM2457 alleviates the onset of osteomyelitis in mice by down-regulating the relative expression of MyD88 and NF-κB relevant inflammation molecules in macrophages.
期刊介绍:
Japanese Journal of Infectious Diseases (JJID), an official bimonthly publication of National Institute of Infectious Diseases, Japan, publishes papers dealing with basic research on infectious diseases relevant to humans in the fields of bacteriology, virology, mycology, parasitology, medical entomology, vaccinology, and toxinology. Pathology, immunology, biochemistry, and blood safety related to microbial pathogens are among the fields covered. Sections include: original papers, short communications, epidemiological reports, methods, laboratory and epidemiology communications, letters to the editor, and reviews.