1、Fluoride physicochemical effects carbonated hydroxylapatite carbonated fluorapatite biologic effects chemical forms,doses,and exposuresFluoridenarrow therapeutic/toxicity window 530 Mbiphasic actionsLow dose -increase bone massHigh dose -reduce bone massgenetic background Fluoride The stimulatory ef
2、fects of sodium fluoride(NaF)on bone formation have been explained solely by its activation of osteoblastsWnt/-catenin signaling pathway F-phosphorylation of glycogen synthase kinase-3 (GSK3)(-)nuclear accumulation of the-catenin runt-related transcription factor 2(Runx2)Wnt/-catenin signaling pathw
3、ay Runx2 signaling pathway Insulin signal pathwayFluoride InsR on steoblastTwist2Runx2insulinBMP/Smad Pathway BMP-2 serine/threonine kinase receptor II serine/threonine kinase receptor I Smads Runx2BMP/Smad Pathway R-Smads +Co-Smads(4)I-Smads necleusBMP/Smad Pathway PERK signaling-ER stress misfolde
4、d and unfolded proteins UPR ER PERK signaling-ER stressF-Toxic effects-NOpentose phosphate oxidative pathwayF-Fibroblast&osteoblast G6PD NADPH NO glutathione reductase intracellular glutathione Fibroblast&osteoblast Fibroblast osteoblast TNF-/BMP-2/bFGF/F-Cbfa1 ALP,OCN,COL I Skin FB Osteoporosis:OB=FBFibroblast&osteoblast Skin FB osteoblast like cell Osteoporosis:OB=FB
