A Chemically Modified Curcumin (CMC 2.24) Inhibits Nuclear Factor kappa B Activation and Inflammatory Bone Loss in Murine Models of LPS-Induced Experimental Periodontitis and Diabetes-Associated Natural Periodontitis

Author(s)

Elburki, Muna S. ; Rossa, Jr., Carlos ; Guimares-Stabili, Morgana R. ; Lee, Hsi-Ming ; Curylofo-Zotti, Fabiana A. ; Johnson, Francis ; Golub, Lorne M.

• Document type: Journal article
• Source: Inflammation; v. 40, n. 4, p. 1436-1449, AUG 2017.
• Web of Science Citations: 9

Abstract

The purpose of this study was to assess the effect of a novel chemically modified curcumin (CMC 2.24) on NF-kappa B and MAPK signaling and inflammatory cytokine production in two experimental models of periodontal disease in rats. Experimental model I: Periodontitis was induced by repeated injections of LPS into the gingiva (3x/week, 3 weeks); control rats received vehicle injections. CMC 2.24, or the vehicle, was administered by daily oral gavage for 4 weeks. Experimental model II: Diabetes was induced in adult male rats by streptozotocin injection; periodontal breakdown then results as a complication of uncontrolled hyperglycemia. Non-diabetic rats served as controls. CMC 2.24, or the vehicle, was administered by oral gavage daily for 3 weeks to the diabetics. Hemimaxillae and gingival tissues were harvested, and bone loss was assessed radiographically. Gingival tissues were pooled according to the experimental conditions and processed for the analysis of matrix metalloproteinases (MMPs) and bone-resorptive cytokines. Activation of p38 MAPK and NF-kappa B signaling pathways was assessed by western blot. Both LPS and diabetes induced an inflammatory process in the gingival tissues associated with excessive alveolar bone resorption and increased activation of p65 (NF-kappa B) and p38 MAPK. In both models, the administration of CMC 2.24 produced a marked reduction of inflammatory cytokines and MMPs in the gingival tissues, decreased bone loss, and decreased activation of p65 (NF-kappa B) and p38 MAPK. Inhibition of these cell signaling pathways by this novel tri-ketonic curcuminoid (natural curcumin is di-ketonic) may play a role in its therapeutic efficacy in locally and systemically associated periodontitis. (AU)

• FAPESP's process: 10/19660-2 - Biological mechanisms of curcumin-mediated modulation of osteoclastogenesis, bone resorption and repair
• Grantee: Morgana Rodrigues Guimarães Stabili
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 12/15826-9 - Modulation of inflammatory bone resorption by a novel chemically modified curcumin: focus on osteoclastogenesis
• Grantee: Fabiana Almeida Curylofo Zotti
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 10/20091-2 - Biological mechanisms of curcumin-mediated modulation of osteoclastogenesis, bone resorption and repair
• Grantee: Carlos Rossa Junior
• Support Opportunities: Regular Research Grants
• FAPESP's process: 09/54080-0 - Acquisition of an in vivo microtomography scanner for use in the Laboratory for Characterization and Evaluation of Biological Responses
• Grantee: Elcio Marcantonio Junior
• Support Opportunities: Multi-user Equipment Program