Wnts are a large family of growth factors that mediate essential biological processes like embryogenesis, morpho- genesis and organogenesis. These proteins also play a role in oncogenesis, and they regulate apoptosis ...Wnts are a large family of growth factors that mediate essential biological processes like embryogenesis, morpho- genesis and organogenesis. These proteins also play a role in oncogenesis, and they regulate apoptosis in many tissues. Wnts bind to a membrane receptor complex comprised of a frizzled （FZD） G-protein-coupled receptor and a low-density lipoprotein （LDL） receptor-related protein （LRP）. The formation of this ligand-receptor complex initiates a number of signaling cascades that include the canonical/beta-catenin pathway as well as several noncanonical pathways. In recent years, canonical Wnt signaling has been reported to play a significant role in the control of bone formation. Clinical studies have found that mutations in LRP-5 are associated with reduced bone mineral density （BMD） and fractures. Investigations of knockout and transgenic mouse models of Wnt pathway components have shown that canonical Wnt signaling modulates most aspects ofosteoblast physiology including proliferation, differentiation, function and apoptosis. Transgenic mice expressing a gain of function mutant of LRP-5 in bone, or mice lacking the Wnt antagonist secreted frizzled-related protein-l, exhibit elevated BMD and suppressed osteoblast apoptosis. In addition, preclinical studies with pharmacologic compounds such as those that inhibit glycogen synthase kinase-3β support the importance of the canonical Wnt pathway in modulation of bone formation and osteoblast apoptosis.展开更多
Objective To study mRNA expression of the mediating-related genes in osteoblasts after expo-sure to Titanium-alloy panicles and cytochalasin-D. Methods Human osteoblasts were isolated from trabecular fragments and exp...Objective To study mRNA expression of the mediating-related genes in osteoblasts after expo-sure to Titanium-alloy panicles and cytochalasin-D. Methods Human osteoblasts were isolated from trabecular fragments and exposed to 0.01% (v/v) titanium-alloy particles for 8h. Pretreatment of osteoblasts with cytochalasin-D(5μmol/L) to prevent phagocytosis prior to the addition of Titanium-alloy particles, mRNA expression of RANKL, OPG, and IL-6 was semi-quantified by RT-PCR. Results Expressions of RANKL, OPG, and IL-6 mRNA at respective levels were found in osteoblasts under normal condition, which did not show significant changes in the samples treated with cytochalasin-D but without particles. Exposure of osteoblasts to particles after being treated with or without cytochalasin-D altered mRNA expression of these genes, however, an increase in the ratio of RANKL/OPG mRNA was only found in samples without cytochalasin-D treatment. Conclusion Changes of expression of RANKL, OPG, and IL-6 mRNA in osteoblasts after exposure to titanium-alloy particles were independent of phagocytosis, whereas phagocytosis has a direct effect on their ability to stimulate osteoclast differentiation and function.展开更多
文摘Wnts are a large family of growth factors that mediate essential biological processes like embryogenesis, morpho- genesis and organogenesis. These proteins also play a role in oncogenesis, and they regulate apoptosis in many tissues. Wnts bind to a membrane receptor complex comprised of a frizzled （FZD） G-protein-coupled receptor and a low-density lipoprotein （LDL） receptor-related protein （LRP）. The formation of this ligand-receptor complex initiates a number of signaling cascades that include the canonical/beta-catenin pathway as well as several noncanonical pathways. In recent years, canonical Wnt signaling has been reported to play a significant role in the control of bone formation. Clinical studies have found that mutations in LRP-5 are associated with reduced bone mineral density （BMD） and fractures. Investigations of knockout and transgenic mouse models of Wnt pathway components have shown that canonical Wnt signaling modulates most aspects ofosteoblast physiology including proliferation, differentiation, function and apoptosis. Transgenic mice expressing a gain of function mutant of LRP-5 in bone, or mice lacking the Wnt antagonist secreted frizzled-related protein-l, exhibit elevated BMD and suppressed osteoblast apoptosis. In addition, preclinical studies with pharmacologic compounds such as those that inhibit glycogen synthase kinase-3β support the importance of the canonical Wnt pathway in modulation of bone formation and osteoblast apoptosis.
文摘Objective To study mRNA expression of the mediating-related genes in osteoblasts after expo-sure to Titanium-alloy panicles and cytochalasin-D. Methods Human osteoblasts were isolated from trabecular fragments and exposed to 0.01% (v/v) titanium-alloy particles for 8h. Pretreatment of osteoblasts with cytochalasin-D(5μmol/L) to prevent phagocytosis prior to the addition of Titanium-alloy particles, mRNA expression of RANKL, OPG, and IL-6 was semi-quantified by RT-PCR. Results Expressions of RANKL, OPG, and IL-6 mRNA at respective levels were found in osteoblasts under normal condition, which did not show significant changes in the samples treated with cytochalasin-D but without particles. Exposure of osteoblasts to particles after being treated with or without cytochalasin-D altered mRNA expression of these genes, however, an increase in the ratio of RANKL/OPG mRNA was only found in samples without cytochalasin-D treatment. Conclusion Changes of expression of RANKL, OPG, and IL-6 mRNA in osteoblasts after exposure to titanium-alloy particles were independent of phagocytosis, whereas phagocytosis has a direct effect on their ability to stimulate osteoclast differentiation and function.
