Assessment of the role of soluble epoxide hydrolase (sEH) in bone metabolism during bone regeneration and senescence

• Grant number: 24/01495-8
• Support Opportunities: Regular Research Grants
• Start date: October 01, 2024
• End date: September 30, 2026
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Marcelo Henrique Napimoga
• Grantee: Marcelo Henrique Napimoga
• Host Institution: Centro de Pesquisas Odontológicas São Leopoldo Mandic. Faculdade São Leopoldo Mandic (SLMANDIC). Sociedade Regional de Ensino e Saúde S/S Ltda (SRES). Campinas , SP, Brazil
• Associated researchers: Elizabeth Ferreira Martinez ; Francisco Humberto Nociti Junior ; Henrique Ballassini Abdalla ; Juliana Trindade Clemente Napimoga ; Mariana Quirino Silveira Soares

Abstract

Our research group has recently concluded the Thematic Research Grant (#17/22334-9), in which, through various published articles, we demonstrated that the inhibition of the soluble epoxide hydrolase (sEH) enzyme has anti-inflammatory effects, thereby hindering the progression of inflammatory osteolytic diseases. sEH inhibition was able to increase the systemic production of Specialized Pro-resolving Mediators (SPMs) (PMID: 36508312), associated with regulatory actions on T cells (PMID: 38117781), favoring the resolution of inflammation and inhibiting the progression of periodontal disease (PMID: 29851077). On the other hand, sEH inhibition modulated the phenotype of regulatory T cells to decrease the impact of rheumatoid arthritis (PMID: 32400048). Additionally, through lipidomic analysis, it demonstrated the ability to reduce various diols that can trigger an inflammatory response, coupled with an increase in anti-inflammatory lipid precursors (PMID: 37984607). However, the potential of sEH enzyme inhibition on bone events associated with cellular senescence, including processes such as bone neoformation and bone quality, remains unknown. Long-chain polyunsaturated fatty acid epoxides (EpFAs) generated by the CYP450 pathway are important bioactive lipids with immunomodulatory actions. In the presence of sEH, these lipids lose their ability to resolve/control the inflammatory process during cellular senescence as well as events related to bone tissue homeostasis. In this context, the current project aims to: Investigate the role of the sEH enzyme in the process of bone neoformation after critical defect in the calvaria. Examine the influence of the absence of the sEH enzyme on mandibular bone levels and parameters. Evaluate inflammatory parameters related to gingival tissue aging in the absence of the sEH enzyme in an in vivo senescence model. Through this project, we hope to elucidate the role played by the sEH enzyme in biological events associated with bone tissue, as well as in controlling the impact of senescence on mineralized tissues. (AU)