ABSTRACT
PURPOSE: The effects of resveratrol administration on calvarial bone defects with alloplastic graft material was investigated for osteoinductive reaction and bone development in rats. METHODS: Healthy male rats were randomly divided into 3 groups consisting of 10 rats. Groups were as follows: control (defect) group, defect + graft group, and defect + graft + resveratrol group. A calvarial bone defect was created in all groups, alloplastic bone grafts were applied to the defect in the 2nd and 3rd group, resveratrol (5 mg/kg/day) was added to the drinking water of the animals following graft application for 28 days in the 3rd group. RESULTS: Increase in osteoclasts and necrotic changes were observed histopathologically in the control group. In the 2nd group, reduction of inflammation, congestion of blood vessels, increased osteblastic activity, osteoinductive effect, progression of osteocyte development and increased collagen fibers in connective tissue were observed. In the 3rd group, osteoblasts seemed to secrete bone matrix and accelerate osteoinductive effect with increased osteopregenitor activity and positive osteopontin and osteonectin expressions. CONCLUSION: Resveratrol treatment was thought to be an alternative and supportive drug for implant application by inducing new bone formation in the calvaral defect region as a result of short-term treatment.
Subject(s)
Bone Regeneration/drug effects , Bone Substitutes/administration & dosage , Bone Transplantation/methods , Resveratrol/administration & dosage , Skull/surgery , Animals , Bone Substitutes/therapeutic use , Disease Models, Animal , Drug Administration Schedule , Male , Osseointegration/drug effects , Osteoblasts/drug effects , Osteogenesis/drug effects , Osteonectin/administration & dosage , Osteopontin/administration & dosage , Rats , Skull/drug effectsABSTRACT
Abstract Purpose: The effects of resveratrol administration on calvarial bone defects with alloplastic graft material was investigated for osteoinductive reaction and bone development in rats. Methods: Healthy male rats were randomly divided into 3 groups consisting of 10 rats. Groups were as follows: control (defect) group, defect + graft group, and defect + graft + resveratrol group. A calvarial bone defect was created in all groups, alloplastic bone grafts were applied to the defect in the 2nd and 3rd group, resveratrol (5 mg/kg/day) was added to the drinking water of the animals following graft application for 28 days in the 3rd group. Results: Increase in osteoclasts and necrotic changes were observed histopathologically in the control group. In the 2nd group, reduction of inflammation, congestion of blood vessels, increased osteblastic activity, osteoinductive effect, progression of osteocyte development and increased collagen fibers in connective tissue were observed. In the 3rd group, osteoblasts seemed to secrete bone matrix and accelerate osteoinductive effect with increased osteopregenitor activity and positive osteopontin and osteonectin expressions. Conclusion: Resveratrol treatment was thought to be an alternative and supportive drug for implant application by inducing new bone formation in the calvaral defect region as a result of short-term treatment.
Subject(s)
Animals , Male , Rats , Skull/surgery , Bone Regeneration/drug effects , Bone Transplantation/methods , Bone Substitutes/administration & dosage , Resveratrol/administration & dosage , Osteoblasts/drug effects , Osteogenesis/drug effects , Skull/drug effects , Drug Administration Schedule , Osteonectin/administration & dosage , Osseointegration/drug effects , Bone Substitutes/therapeutic use , Disease Models, Animal , Osteopontin/administration & dosageABSTRACT
It is known that SPARC gates VEGF-A signal transduction towards KDR, the primary angiogenic VEGF receptor. We sought to determine whether inhibition of SPARC activity using anti-SPARC peptide could inhibit laser-induced CNV by promoting binding of VEGF-A to FLT-1. We created anti-SPARC l-peptide and retro-inverso anti-SPARC d-peptide. Anti-SPARC peptides or PBS were injected intravitreally 1day before or after laser induction. Intravitreal injection of anti-SPARC l-peptide 1day before laser induction promotes FLT-1 phosphorylation and inhibited laser-induced CNV and anti-SPARC d-peptide had no effect. Injection 1day after laser injury did not affect size of laser-induced CNV. Inhibition of SPARC activity could be complementary to existing anti-CNV therapy.
Subject(s)
Choroidal Neovascularization/metabolism , Oligopeptides/metabolism , Osteonectin/antagonists & inhibitors , Animals , Choroidal Neovascularization/pathology , Disease Models, Animal , Intravitreal Injections , Lasers/adverse effects , Mice , Mice, Inbred BALB C , Osteonectin/administration & dosage , Phosphorylation , Vascular Endothelial Growth Factors/metabolismABSTRACT
Overcoming resistance to chemotherapy and radiation therapy has been a difficult but important goal in the effort to cure cancer. We used gene-expression microarrays to identify differentially expressed genes involved in colorectal cancer resistance to chemotherapy and identified secreted protein, acidic and rich in cysteine (osteonectin) (SPARC) as a putative resistance-reversal gene by demonstrating low SPARC expression in refractory human MIP101 colon cancer cells. We were able to achieve restoration of their radiosensitivity and sensitivity to 5-fluorouracil and irinotecan by reexpression of SPARC in tumor xenografts. Moreover, treatment of mice with SPARC conferred increased sensitivity to chemotherapy and led to significant regression of xenografted tumors. The results show that modulation of SPARC expression affects colorectal cancer sensitivity to radiation and chemotherapy. SPARC-based gene or protein therapy may ameliorate the emergence of resistant clones and eradicate existing refractory clones and offers a novel approach to treating cancer.
Subject(s)
Antineoplastic Agents/administration & dosage , Camptothecin/analogs & derivatives , Colonic Neoplasms/drug therapy , Drug Resistance, Neoplasm/drug effects , Neoplasms, Experimental/drug therapy , Osteonectin/administration & dosage , Animals , Camptothecin/administration & dosage , Cell Line, Tumor , Colonic Neoplasms/metabolism , Colonic Neoplasms/pathology , Fluorouracil/administration & dosage , Gene Expression Profiling , Gene Expression Regulation, Neoplastic/drug effects , Humans , Irinotecan , Mice , Mice, Nude , Neoplasms, Experimental/metabolism , Neoplasms, Experimental/pathology , Oligonucleotide Array Sequence Analysis , Osteonectin/metabolism , Transplantation, HeterologousABSTRACT
It is urgently necessary to clarify functions of uncharacterized proteins. To understand life processes, we must investigate the functions and networks of proteins expressed from genomic DNA. In the near future, microinfusion experiments will become a more important method for analyzing uncharacterized function of proteins in vivo. Here we provide a practical manual for performing microinfusion experiments in mice. We also describe our experiment in which we performed a single injection of morphine following Secreted Protein Acidic and Rich in Cysteine (SPARC) infusion into the basolateral amygdala of previously uninjected mice and found markedly enhanced locomotor activity. We discuss the utility of microinfusion experiments in mice.
Subject(s)
Microinjections/methods , Pharmacology/methods , Animals , Mice , Morphine/administration & dosage , Morphine/pharmacology , Motor Activity/drug effects , Osteonectin/administration & dosage , Osteonectin/genetics , RNA, Messenger/metabolism , Up-RegulationABSTRACT
Repeated administration of morphine substantially increases its locomotor-enhancing activity, a phenomenon termed locomotor sensitization. Here we show that secreted protein acidic and rich in cysteine (SPARC), an anti-adhesive glycoprotein present in the basolateral amygdala, contributes to the establishment of locomotor sensitization. The morphine-induced increase in SPARC levels in the basolateral amygdala persisted after morphine withdrawal and coincided with the duration of locomotor sensitization. Moreover, a single injection of morphine after SPARC infusion into the basolateral amygdala of previously uninjected mice substantially enhanced locomotor activity. Thus, SPARC may be an important element for establishing locomotor sensitization to morphine.
