ABSTRACT
Purpose: Metabolic associated fatty liver disease is a novel concept defined as fatty liver associated with metabolic disorders. We investigated the effect of metabolic associated fatty liver disease on hepatocellular carcinoma patient mortality. Patients and Methods: A total of 624 patients with hepatocellular carcinoma between 2012 and 2020 were enrolled in this retrospective study. Hepatic steatosis was diagnosed using computed tomography or magnetic resonance imaging. Metabolic associated fatty liver disease was defined based on the proposed criteria in 2020. Propensity score matching was performed for patients with metabolic associated fatty liver disease and those without the condition. A Cox proportional hazards regression model was used to evaluate the association between metabolic associated fatty liver disease and hepatocellular carcinoma patient outcomes. Results: Patients with hepatocellular carcinoma and metabolic associated fatty liver disease tended to achieve better outcomes than did those without metabolic associated fatty liver disease after matching (p<0.001). Metabolic associated fatty liver disease was significantly associated with better prognosis in patients with concurrent hepatitis B infection (p<0.001). Moreover, high levels of hepatitis B viral DNA in serum samples was associated with a significantly increased risk of death in patients without non-metabolic associated fatty liver disease (p=0.045). Additionally, the association between metabolic associated fatty liver disease and survival in hepatitis B virus-related hepatocellular carcinoma was similar in all subgroups based on metabolic traits. Conclusion: Metabolic associated fatty liver disease increases the survival rate of patients with hepatocellular carcinoma and hepatitis B virus infection. The potential interaction of steatosis and virus replication should be considered for future research and clinical treatment strategies.
ABSTRACT
The objective of this study was to evaluate symptoms of depression and anxiety as well as changes in spontaneous neuronal activity in college students studying abroad during the coronavirus 2019 (COVID-19) pandemic. We examined functional brain changes using resting-state functional magnetic resonance imaging (fMRI), the amplitude of low-frequency fluctuations (ALFF), and regional homogeneity (ReHo) in overseas students with enforced isolation due to the COVID-19 pandemic. Additionally, emotional assessments were administered to determine the severity of depression and anxiety. The questionnaire results showed that anxiety and depressive symptoms differed between overseas students (i.e., those attending an overseas college virtually) and local students (i.e., those attending a local college in person). The fMRI data revealed higher ALFF values in the bilateral superior medial frontal gyrus, bilateral pre-central gyrus, left insula, and left superior temporal gyrus as well as lower ALFF values in the bilateral paracentral lobule (supplementary motor area) in overseas students. Moreover, ReHo analysis also revealed significant differences between overseas students and local students. Compared with local students, overseas students showed significantly increased ReHo in the right inferior frontal and superior temporal gyri and decreased ReHo in the bilateral paracentral lobule, bilateral superior medial frontal gyrus (supplementary motor area), and bilateral pre-central gyrus. In addition, in overseas students, altered ReHo in the cluster including the left superior and medial frontal gyri, pre-central gyrus, and paracentral lobule was significantly positively correlated with Self-Rating Depression Scale scores. Thus, spontaneous brain activity in overseas students changed during the COVID-19 pandemic. This change in brain function might be related to depression and anxiety symptoms. These results suggest that mental health services are needed to decrease the risk of anxiety and depression among college students studying abroad during the COVID-19 pandemic.
ABSTRACT
The collapse lake area due to coal mining in Huaibei shows high biodiversity, but the bacterial community composition and diversity in the lake sediments are still rarely studied. Therefore, based on 16S rRNA high-throughput sequencing and combined with analysis of environmental factors, we comparatively analyzed the bacterial community composition and diversity of surface sediments from East Lake (DH) and South Lake (NH) and Middle Lake (ZH) in the collapse lake area of Huaibei. The bacterial community compositions are significantly different in the sediments among Huaibei collapsed lakes, with DH having the largest number of species, and NH having a higher species diversity. Pseudomonadota is the most abundant phylum in the sediments of DH and NH, while the most abundant phyla in ZH are Bacteroidales, Chloroflexales, Acidobacteriales, and Firmicutes. Anaerolineae (24.05% ± 0.20%) is the most abundant class in the DH sediments, and Gammaproteobacteria (25.94% ± 0.40%) dominates the NH sediments, Bacteroidia (32.12% ± 1.32%) and Clostridia (21.98% ± 0.90%) contribute more than 50% to the bacteria in the sediments of ZH. Redundancy analysis (RDA) shows that pH, TN, and TP are the main environmental factors affecting the bacterial community composition in the sediments of the collapsed lake area. The results reveal the bacterial community composition and biodiversity in the sediments of the Huaibei coal mining collapsed lakes, and provide new insights for the subsequent ecological conservation and restoration of the coal mining collapsed lakes.
Subject(s)
Geologic Sediments , Lakes , Bacteria/genetics , Biodiversity , China , Firmicutes/genetics , Geologic Sediments/microbiology , Lakes/microbiology , Phylogeny , RNA, Ribosomal, 16S/geneticsABSTRACT
OBJECTIVES: To determine the value of gadobenate dimeglumine (Gd-BOPTA)-enhanced magnetic resonance imaging (MRI) from the hepatobiliary phase for predicting poor outcome in acute-on-chronic liver failure (ACLF) patients. METHODS: In this single-center retrospective study, 74 patients diagnosed as ACLF who underwent Gd-BOPTA-enhanced hepatobiliary magnetic resonance imaging were collected. The quantitative liver-spleen contrast ratio (Q-LSC) and the relative enhancement ratio of the biliary system (REB) at the hepatobiliary phase were measured. Cox proportional hazards regression models were used to evaluate prognostic factors. The capacity of the Q-LSC and REB to predict the 90-day outcome was evaluated via receiver operating characteristic (ROC) curve. RESULTS: During the follow-up period, twenty-eight of 74 ACLF patients (38%) had a poor outcome. The Q-LSC and REB were significant predictive factors (hazard ratio [HR] = 0.03 [0.002-0.54], p < 0.05; HR = 0.07 [0.01-0.88], p < 0.05) for prognosis in patients with ACLF. Moreover, the areas under the ROC curves of Q-LSC and REB for predicting poor outcome in patients with ACLF were 0.81 and 0.80, respectively. The most appropriate cutoff values for the Q-LSC and REB were 1.09 and 0.57, respectively. The ACLF patients with the Q-LSC ≤ 1.09 or REB ≤ 0.57 had a low cumulative survival. CONCLUSIONS: Gd-BOPTA-enhanced hepatobiliary phase MR imaging can predict poor outcome in patients with acute-on-chronic liver failure. KEY POINTS: ⢠The quantitative liver-spleen contrast ratio at the hepatobiliary phase was a significant predictive prognostic factor in patients with acute-on-chronic liver failure. ⢠The relative enhancement ratio of the biliary system at the hepatobiliary phase was a significant prognostic factor in patients with acute-on-chronic liver failure. ⢠Gadobenate dimeglumine contrast-enhanced MR imaging from the hepatobiliary phase can predict poor outcome in patients with acute-on-chronic liver failure.
Subject(s)
Acute-On-Chronic Liver Failure , Organometallic Compounds , Acute-On-Chronic Liver Failure/diagnostic imaging , Contrast Media/pharmacology , Gadolinium DTPA , Humans , Liver/diagnostic imaging , Magnetic Resonance Imaging/methods , Meglumine/analogs & derivatives , Prognosis , Retrospective StudiesABSTRACT
BACKGROUND: Long non-coding RNAs (lncRNAs) are found to involve in modulating the development of atherosclerosis (AS). But the molecular mechanism of lncRNA growth-arrest specific transcript 5 (GAS5) in AS is not fully understood. METHODS: QRT-PCR was performed to measure the abundances of GAS5, miR-128-3p and fibulin 2 (FBLN2). Oxidized low-density lipoprotein (ox-LDL)-treated THP-1 cells were employed as cell models of AS. The cell proliferation and apoptosis were analyzed using CCK-8 and Flow cytometry assays, respectively. Levels of all protein were examined by western blot. The interaction among GAS5, miR-128-3p and FBLN2 was confirmed via dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. RESULTS: GAS5 was elevated and miR-128-3p was decreased in the serum of patients with AS and ox-LDL-stimulated THP-1 cells. Ox-LDL stimulation inhibited proliferation and induced apoptosis of THP-1 cells. Meanwhile, GAS5 directly targeted miR-128-3p and inversely modulated its expression. Importantly, GAS5 depletion facilitated cell proliferation and impaired apoptosis in ox-LDL-induced THP-1 cells. Additionally, GAS5 augmented FBLN2 expression through sponging miR-128-3p, and miR-128-3p facilitated proliferation and retarded apoptosis of ox-LDL-induced THP-1 cells by targeting FBLN2. CONCLUSION: GAS5 knockdown promoted the growth of ox-LDL-induced THP-1 cells through down-modulating FBLN2 and increasing miR-128-3p, suggesting the potential value of GAS5 for treatment of AS.
Subject(s)
Lipoproteins, LDL/metabolism , MicroRNAs/metabolism , RNA, Long Noncoding/metabolism , THP-1 Cells/metabolism , Cell Proliferation , Humans , RNA, Long Noncoding/genetics , TransfectionABSTRACT
BACKGROUND: The aim of the study was to evaluate the change of subchondral bone collagen and trabecular bone in the weight-bearing area of femoral head from patients with osteoarthritis (OA) or osteonecrosis of femoral head (ONFH), and discuss the effect of collagen degradation on OA and ONFH. METHODS: Femoral heads from patients with femoral neck fracture (FNF) were collected as control group. All collected samples were divided into OA group (N = 10), ONFH group (N = 10), and FNF group (N = 10). Differences of subchondral bone collagen were compared through scanning electron microscope (SEM) observation, immunohistochemistry staining, and Masson's trichrome staining. Alteration of subchondral bone was displayed through hematoxylin and eosin (H&E) staining and gross morphology. RESULTS: SEM results showed that collagen fibers in OA and ONFH group appeared to be thinner, rougher, sparser, and more wizened. Immunohistochemistry and Masson's trichrome staining results demonstrated that the content of collagen fibers in the OA and ONFH group was obviously less than the FNF group. H&E staining results showed that trabecular bone in OA and ONFH group appeared to be thinner and ruptured. Gross morphology results showed that the degeneration and destruction of cartilage and subchondral bone in OA and ONFH group were severer than FNF group. The characteristics mentioned above in ONFH group were more apparent than OA group. CONCLUSIONS: This study revealed that degradation of collagen fibers from subchondral bone in the weight-bearing area of femoral head was associated with OA and ONFH, which may help to find new therapeutic strategies of the diseases.
Subject(s)
Collagen/metabolism , Femur Head Necrosis/metabolism , Femur Head/metabolism , Osteoarthritis/metabolism , Proteolysis , Weight-Bearing/physiology , Aged , Cancellous Bone/metabolism , Cancellous Bone/physiopathology , Female , Femur Head/physiopathology , Femur Head Necrosis/physiopathology , Humans , Male , Middle Aged , Osteoarthritis/physiopathologyABSTRACT
PURPOSE: Aseptic loosening is a major complication after total joint replacement. Reactive oxygen species generated by local tissue cells and liberated from implant surfaces have been suggested to cause implant failures. Surface modification of titanium (Ti)-based implants with proanthocyanidins (PAC) is a promising approach for the development of anti-oxidant defense mechanism to supplement the mechanical functions of Ti implants. In this study, a controlled PAC release system was fabricated on the surface of Ti substrates using the layer-by-layer (LBL) assembly. MATERIALS AND METHODS: Polyethyleneimine (PEI) base layer was fabricated to enable layer-by-layer (LBL) deposition of hyaluronic acid/chitosan (HA/CS) multi-layers without or with the PAC. Surface topography and wettability of the fabricated HA/CS-PAC substrates were characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM), Fourier-transform infrared spectroscopy (FTIR) and contact angle measurement. PAC release profiles were investigated using drug release assays. MC3T3-E1 pre-osteoblast cells were used to assess the osteo-inductive effects of HA/CS-PAC substrates under conditions H2O2-induced oxidative stress in vitro. A rat model of femoral intramedullary implantation evaluated the osseo-integration and osteo-inductive potential of the HA/CS-PAC coated Ti implants in vivo. RESULTS: SEM, AFM, FTIR and contact angle measurements verified the successful fabrication of Ti surfaces with multi-layered HA/CS-PAC coating. Drug release assays revealed controlled and sustained release of PAC over 14 days. In vitro, cell-based assays showed high tolerability and enhanced the osteogenic potential of MC3T3-E1 cells on HA/CS-PAC substrates when under conditions of H2O2-induced oxidative stress. In vivo evaluation of femoral bone 14 days after femoral intramedullary implantation confirmed the enhanced osteo-inductive potential of the HA/CS-PAC coated Ti implants. CONCLUSION: Multi-layering of HA/CS-PAC coating onto Ti-based surfaces by the LBL deposition significantly enhances implant osseo-integration and promotes osteogenesis under conditions of oxidative stress. This study provides new insights for future applications in the field of joint arthroplasty.
Subject(s)
Antioxidants/pharmacology , Osteogenesis/drug effects , Proanthocyanidins/pharmacology , Prostheses and Implants , Titanium/pharmacology , Animals , Apoptosis/drug effects , Cell Differentiation/drug effects , Cell Line , Cell Proliferation/drug effects , Chitosan/chemistry , Drug Liberation , Female , Hyaluronic Acid/chemistry , Hydrogen Peroxide/pharmacology , Intracellular Space/metabolism , Mice , Osseointegration/drug effects , Osteoblasts/cytology , Osteoblasts/drug effects , Polyethyleneimine/chemistry , Rats, Sprague-Dawley , Reactive Oxygen Species/metabolism , Tumor Suppressor Protein p53/metabolism , Wettability , X-Ray MicrotomographyABSTRACT
Osteoporosis is a severe health problem causing bone fragility and consequent fracture. Titanium (Ti) implants, used in patients with osteoporotic fractures, are prone to failure because of the decreased bone mass and strength. Therefore, it is of utmost importance to fabricate implants possessing osteogenic properties to improve implant osseointegration. To improve the long-term survival rate of Ti implants in osteoporotic patients, hyaluronic acid/ϵ-polylysine multilayers containing the parathyroid hormone (PTH)-related protein (PTHrP) were deposited on Ti implants by a layer-by-layer (LBL) electro assembly technique. The murine pre-osteoblast cell line MC3T3-E1, possessing a high potential of osteoblast differentiation, was used to evaluate the osteo-inductive effects of Ti-LBL-PTHrP in vitro. In addition, the performance of the Ti (Ti-LBL-PTHrP) implant was evaluated in vivo in a femoral intramedullary implantation in Sprague Dawley rats. The Ti-LBL-PTHrP implant regulated the release of the loaded PTHrP to increase bone formation in the early stage of implantation. The in vitro results revealed that cells on Ti-LBL-PTHrP did not show any evident proliferation, but a high level of alkaline phosphatase activity and osteoblast-related protein expression was found, compared to the uncoated Ti group (p < 0.05). In addition, in vivo micro-CT and histological analysis demonstrated that the Ti-LBL-PTHrP implants could significantly promote the formation and remodeling of new bone in osteoporotic rats at 14 d after implantation. Overall, this study established a profound and straightforward methodology for the manufacture of biofunctional Ti implants for the treatment of osteoporosis.
Subject(s)
Osteogenesis , Osteoporosis/drug therapy , Osteoporosis/surgery , Parathyroid Hormone/metabolism , Titanium/chemistry , 3T3 Cells , Alkaline Phosphatase/metabolism , Animals , Biomimetics , Bone and Bones/physiology , Cell Differentiation/drug effects , Female , Femur/surgery , Mice , Osseointegration/drug effects , Osteoblasts/metabolism , Prostheses and Implants , Rats , Rats, Sprague-Dawley , Spectroscopy, Fourier Transform Infrared , Surface Properties , X-Ray MicrotomographyABSTRACT
Osteoporosis is caused by disturbance in the dynamic balance of bone remodelling, a physiological process, vital for maintenance of healthy bone tissue in adult humans. In this process, a new bone is formed by osteoblasts and the pre-existing bone matrix is resorbed by osteoclasts. Imperatorin, a widely available and inexpensive plant extract with antioxidative and apoptotic effects, is reported to treat osteoporosis. However, the underlying mechanism and specific effects on bone metabolism have not been elucidated. In this study, we used rat bone marrow-derived mesenchymal stem cells and found that imperatorin can activate RUNX2, COL1A1 and osteocalcin by promoting the Ser9 phosphorylation of GSK3ß and entry of ß-catenin into the nucleus. Imperatorin also enhanced the production of phospho-AKT (Ser473), an upstream factor that promotes the Ser9 phosphorylation of GSK3ß. We used ipatasertib, a pan-AKT inhibitor, to inhibit the osteogenic effect of imperatorin, and found that imperatorin promotes osteogenesis via AKT/GSK3ß/ß-catenin pathway. Next, we used rat bone marrow-derived monocytes, to check whether imperatorin inhibits osteoclast differentiation via AKT/GSK3ß/ß-catenin pathway. Further, we removed the bilateral ovaries of rats to establish an osteoporotic model. Intragastric administration of imperatorin promoted osteogenesis and inhibited osteoclast in vivo. Our experiments showed that imperatorin is a potential drug for osteoporosis treatment.
Subject(s)
Furocoumarins/pharmacology , Glycogen Synthase Kinase 3 beta/metabolism , Osteoclasts/drug effects , Osteogenesis/drug effects , Proto-Oncogene Proteins c-akt/metabolism , Wnt Signaling Pathway/drug effects , beta Catenin/metabolism , Animals , Cell Differentiation/drug effects , Collagen Type I , Collagen Type I, alpha 1 Chain , Core Binding Factor Alpha 1 Subunit/metabolism , Male , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/metabolism , Osteoblasts/drug effects , Osteoblasts/metabolism , Osteocalcin/drug effects , Osteocalcin/metabolism , Osteoclasts/metabolism , Osteoporosis/drug therapy , Osteoporosis/metabolism , Piperazines/pharmacology , Pyrimidines/pharmacology , Rats , Rats, Sprague-Dawley , Wnt Signaling Pathway/physiologyABSTRACT
Accumulating evidence suggests that the degradation and resorption of calcium phosphate ceramics is always relatively slow, which may inhibit calcium phosphate ceramics' replacement by new bone tissues and the ultimate bone defect repair. Bone morphogenetic proteins (BMPs) and Teriparatide (PTH) are extensively applied in the treatment of bone pathologies, while their effects on the degradation of calcium phosphate ceramics is limited. In this study, we tested the effects of BMP and PTH on degradation of ß-tricalcium phosphate (ß-TCP) ceramics and bone formation on ß-TCP in ovariectomized (OVX) rat models. After establishment of femur defect model on OVX rats, the BMP + PTH group's rats were injected Teriparatide (30 µg/kg) subcutaneous every other day, while rats of control group and group BMP were injected equal-to-group volume sterilized saline water. Twelve weeks after femur surgery, all rats were sacrificed for Micro-CT scanning and histology tests. The results showed that BMP facilitated degradation of ß-TCP and new bone formation on ß-TCP ceramics. And PTH showed an additional effect on degradation of ß-TCP when combined with BMP. In addition, the results explained that PTH promoted the remodeling of the bone callus occurred during repair.
Subject(s)
Biocompatible Materials/metabolism , Bone Morphogenetic Protein 2/administration & dosage , Calcium Phosphates/metabolism , Osteogenesis/drug effects , Osteoporosis, Postmenopausal/metabolism , Teriparatide/administration & dosage , Animals , Drug Therapy, Combination , Female , Humans , Osteogenesis/physiology , Osteoporosis, Postmenopausal/drug therapy , Osteoporosis, Postmenopausal/pathology , Ovariectomy/adverse effects , Ovariectomy/trends , Random Allocation , RatsABSTRACT
Osteoporosis is accompanied by insufficient osteogenic capacity. Several lines of evidence suggested that solutions to enhance osteoblastogenesis were important strategies for osteoporotic bone defect repair. This study investigated the effect of combined treatment with vitamin K2 and PTH on bone formation in calvarial bone defect in osteoporotic rats and its influence on osteoblast in vitro. Bilateral ovariectomy was used in SPF Sprague Dawley rats to generate an osteoporosis model. Subsequently, a calvarial defect model was established and all osteoporotic rats were randomly assigned to the following groups: control, VK (vitamin K2, 30 mg/kg everyday), PTH (recombinant human PTH (1-34), 60 µg/kg, three times a week) or VK + PTH (vitamin K2, 30 mg/kg everyday plus PTH, 60 µg/kg three times a week) for 8 weeks. In vitro, bone marrow-derived stem cells (BMSCs) were cultured and treated with vitamin K2, PTH or vitamin K2+PTH. ALP staining and western blot were performed to observe the influence of combined treatment on BMSCs. Bone formation within calvarial defect were assessed by serum γ-carboxylated osteocalcin (Gla-OC), micro-CT, histological and immunofluorescent labeling. In this study, combined treatment of PTH and vitamin K2 showed positive effects on preventing bone loss in femurs in OVX rats. Combined treatment increased serum Gla-OC and promoted bone formation in osteoporotic calvarial bone defects. Immunohistochemistry showed that OCN and RUNX2 were more highly expressed in the VK + PTH group than in the control groups. In vitro studies results suggested that combined treatment with PTH and vitamin K2 increased expression of ALP, BMP2 and RUNX2 in BMSCs. Our data suggested that the combination of vitamin K2 and PTH increased differentiation of osteoblast and had a synergistic effect on bone formation in osteoporotic calvarial bone defect.
Subject(s)
Cell Differentiation/drug effects , Osteogenesis/drug effects , Parathyroid Hormone/pharmacology , Vitamin K 2/pharmacology , Animals , Biomarkers/blood , Bone Marrow Cells/cytology , Collagen Type I/blood , Core Binding Factor Alpha 1 Subunit/metabolism , Female , Femur/diagnostic imaging , Femur/metabolism , Femur/pathology , Humans , Osteoblasts/cytology , Osteoblasts/drug effects , Osteoblasts/metabolism , Osteocalcin/metabolism , Ovariectomy , Parathyroid Hormone/genetics , Parathyroid Hormone/metabolism , Peptide Fragments/blood , Rats , Rats, Sprague-Dawley , Recombinant Proteins/biosynthesis , Recombinant Proteins/isolation & purification , Recombinant Proteins/pharmacology , Stem Cells/cytology , Stem Cells/drug effects , Stem Cells/metabolism , X-Ray MicrotomographyABSTRACT
Accumulating evidence suggests that improvements in osteogenesis and angiogenesis play an important role in repairing osteoporotic bone defects. Cinnamomum cassia (C. cassia), a traditional Chinese medicinal herb, is reported to show anabolic effects on osteoblasts. However, whether C. cassia could actually repair bone defects in osteoporotic conditions remains unknown. The purpose of this study was to evaluate the effect of combined treatment with Cinnamaldehyde (main oil isolated from the C. cassia) and ß-tricalcium phosphate (ß-TCP) on bone formation and angiogenesis in critical size calvarial defects in ovariectomized (OVX) rats. Using a previously established OVX model, 5 mm critical size calvarial defect was established in OVX rats. All OVX rats were then randomly divided into OVX group (OVX rats + empty defect), TCP group (OVX rats + ß-TCP), and CTCP group (Cinnamaldehyde 75 mg/kg/day for 12 weeks + ß-TCP). Twelve weeks after treatment, according to Micro-CT and HE staining, combination of Cinnamaldehyde and ß-TCP had an additive effect on bone regeneration compared with other groups (p < 0.05). Based on dynamic fluorochrome-labelling analysis, Cinnamaldehyde+ß-TCP continuously promoted new bone mineralization compared with other groups at each time point (p < 0.05). Microfil perfusion suggested that CTCP group showed more neovascularization compared with other groups (p < 0.05). Immunohistochemical assay supported the findings that Cinnamaldehyde+ß-TCP enhanced expression of OCN, VEGF and CD31. The present study demonstrated that combined treatment with Cinnamaldehyde and ß-TCP promoted bone formation and angiogenesis in osteoporotic bone defects, which provides a promising new strategy for repairing bone defects in osteoporotic conditions.
Subject(s)
Acrolein/analogs & derivatives , Angiogenesis Inducing Agents/administration & dosage , Calcium Phosphates/administration & dosage , Osteogenesis/drug effects , Osteoporosis/drug therapy , Ovariectomy/adverse effects , Acrolein/administration & dosage , Animals , Biocompatible Materials/administration & dosage , Drug Therapy, Combination , Female , Osteogenesis/physiology , Osteoporosis/diagnostic imaging , Osteoporosis/metabolism , Ovariectomy/trends , Rats , Rats, Sprague-Dawley , Skull/diagnostic imaging , Skull/drug effects , Skull/metabolismABSTRACT
PURPOSE: The aim of this study was to evaluate the effect of combining human parathyroid hormone (1-34) (PTH1-34; PTH) and menaquinone-4 (MK-4) on calvarial bone defect repair in osteopenic rats. METHODS: Fourteen week olds were subject to craniotomy for the establishment of osteopenic animal models fed through a chronically low-protein diet. After that, critical calvarial defect model was established and all rats were randomly divided into four groups: sham, MK-4, PTH, and PTH + MK-4. The animals received MK-4 (30 mg/kg/day), PTH1-34 (60 µg/kg, three times a week), or PTH1-34 (60 µg/kg, three times a week) plus MK-4 (30 mg/kg/day) for 8 weeks, respectively. Serum γ-carboxylated osteocalcin (Gla-OC) levels, histological and immunofluorescent labeling were employed to evaluate the bone formation and mineralization in calvarial bone defect. In addition, Microfil perfusion, immunohistochemical, and micro-CT suggested enhanced angiogenesis and bone formation in calvarial bone healing. RESULTS: In this study, treatment with either PTH1-34 or MK-4 promoted bone formation and vascular formation in calvarial bone defects compared with the sham group. In addition, combined treatment of PTH1-34 plus MK-4 increased serum level of Gla-OC, improved vascular number and vascular density, and enhanced bone formation in calvarial bone defect in osteopenic conditions as compared with monotherapy. CONCLUSIONS: In summary, this study indicated that PTH1-34 plus MK-4 combination therapy accelerated bone formation and angiogenesis in calvarial bone defects in presence of osteopenia.
Subject(s)
Bone Diseases, Metabolic/drug therapy , Neovascularization, Physiologic/drug effects , Osteogenesis/drug effects , Parathyroid Hormone/administration & dosage , Skull/drug effects , Vitamin K 2/analogs & derivatives , Animals , Bone Diseases, Metabolic/complications , Bone Diseases, Metabolic/diagnosis , Bone Diseases, Metabolic/pathology , Drug Therapy, Combination , Female , Fracture Healing/drug effects , Fractures, Spontaneous/diagnosis , Fractures, Spontaneous/drug therapy , Fractures, Spontaneous/etiology , Fractures, Spontaneous/pathology , Rats , Rats, Sprague-Dawley , Skull/diagnostic imaging , Skull/injuries , Skull/pathology , Skull Fractures/diagnosis , Skull Fractures/drug therapy , Skull Fractures/etiology , Skull Fractures/pathology , Vitamin K 2/administration & dosage , X-Ray MicrotomographyABSTRACT
The study was to investigate the effect of combining treatment with cinnamaldehyde and parathyroid hormone (1-34) (PTH) on glucocorticoid-induced osteoporosis (GIO) and compare with monotherapy. Forty Sprague-Dawley male rats with GIO were divided into four groups randomly: control group (CON group, N = 10); group that intragastric administration with cinnamaldehyde (CIN group, N = 10); group that subcutaneous injection with PTH, three times per week(PTH group, N = 10); both administration with cinnamaldehyde and PTH (CIN + PTH group, N = 10). Distal femurs were harvested for hematoxylin and eosin (H&E) staining, micro-CT scanning and immunohistochemical analysis. Murine mesenchymal stem cells were cultured and dealt with the presence of dexamethasone(DEX group), DEX + cinnamaldehyde(DEX + CIN group), DEX + PTH(DEX + PTH group) or DEX + cinnamaldehyde + PTH(DEX + CIN + PTH group). Alkaline phosphatase (ALP) staining was performed subsequently. The results showed that bone formation in CIN + PTH group was notably promoted compared with other groups. And the expression of tartrate-resistant acid phosphatase (trap) and runt-related transcription factor 2 (runx2) in CIN + PTH group were down-regulated and up-regulated respectively compared with PTH group. In vitro study revealed that ALP-positive cell number in DEX + CIN + PTH group was obviously enhanced compared with other groups. The study revealed that combined treatment with cinnamaldehyde and PTH enhances the therapeutic effect on GIO through inhibiting osteoclastogenesis and promoting osteoblastogenesis.
Subject(s)
Acrolein/analogs & derivatives , Osteoblasts/drug effects , Osteogenesis/drug effects , Osteoporosis/drug therapy , Parathyroid Hormone/therapeutic use , Acrolein/therapeutic use , Animals , Cells, Cultured , Drug Therapy, Combination , Glucocorticoids/adverse effects , Male , Mesenchymal Stem Cells/drug effects , Mice , Osteoporosis/chemically induced , Rats , Rats, Sprague-DawleyABSTRACT
To explore the effect of cinnamaldehyde on the distal femur in ovariectomized rats and its influence on osteoblast in vitro. Female Sprague-Dawley rats which underwent either bilateral ovariectomy or sham operation were divided into five groups randomly: group OVX (OVX, N = 10) and group sham (SHAM, N = 10) received normal saline (NS) by gavage at a dose of 50 ml/kg·d; group low dose, group middle dose and group high dose received cinnamaldehyde by gavage at a dose of 25 mg/kg·d (OLD, N = 10), 50 mg/kg·d (OMD, N = 10), and 75 mg/kg·d (OHD, N = 10) respectively. Distal femurs were harvested for hematoxylin and eosin (HE) staining, micro-ct scanning and immunohistochemical analysis. Murine mesenchymal stem cells were cultured and dealt with the presence of either cinnamaldehyde at a dose of 15ug/ml (OLD), 30ug/ml (OMD), 60ug/ml (OHD) or vehicle. ALP staining and western blot were performed to observe the influence of cinnamaldehyde on the differentiation of osteoblast. HE and micro-ct results indicated that osteogenesis were promoted with the treatment of cinnamaldehyde. Immunohistochemical results showed that cinnamaldehyde increased the number of osteoblast and decreased the number of osteoclast. In vitro studies indicated that cinnamaldehyde promoted expression of alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2), osteocalcin (OCN) and collagen type IÉ1 (COL1É1). The treatment effect behaved as dose-dependently. Thus, cinnamaldehyde inhibits osteoclastogenesis and promotes osteoblastogenesis, and may plays an important role in the treatment of osteoporosis clinically.
Subject(s)
Acrolein/analogs & derivatives , Cell Differentiation/drug effects , Osteoblasts/physiology , Osteogenesis/drug effects , Ovariectomy , Acrolein/administration & dosage , Acrolein/pharmacology , Alkaline Phosphatase/genetics , Alkaline Phosphatase/metabolism , Animals , Cells, Cultured , Collagen Type I/metabolism , Collagen Type I, alpha 1 Chain , Core Binding Factor Alpha 1 Subunit/genetics , Core Binding Factor Alpha 1 Subunit/metabolism , Depression, Chemical , Dose-Response Relationship, Drug , Female , Gene Expression/drug effects , Mice , Osteocalcin/genetics , Osteocalcin/metabolism , Osteoclasts/physiology , Osteoporosis/drug therapy , Phytotherapy , Rats, Sprague-Dawley , Stimulation, ChemicalABSTRACT
Chitosan Oligosaccharide (COS) has been widely used for the systemic treatment of clinical diseases such as bone tissue engineering. However, its influence on osteoclast formation, which plays a critical role in bone homeostasis, has never been investigated. The aim of this study was to investigate the effect of chitosan oligosaccharide on differentiation of osteoclast. Using cell counting kit-8, tartrate-resistant acid phosphatase staining, reverse transcriptionquantitative polymerase chain reaction assay and western blot analysis, we demonstrated that chitosan oligosaccharide cannot inhibit RANKL-induced osteoclast precursor proliferation but does promote osteoclast differentiation by stimulating the activation of p38/mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK)/MAPK, extracellular signal-regulated kinase (ERK)/MAPK and protein kinase B (AKT) without affecting nuclear factor kappaB (NF-kB) signaling pathways. Based on the promoting effect of chitosan oligosaccharide on osteoclast differentiation, we suggest that this property of chitosan oligosaccharide may have potential detrimental effect on bone homeostasis.