ABSTRACT
Previous studies have demonstrated the beneficial effect of melatonin (MEL) on bone tissue and bone metabolism. Rapamycin (RAP) promotes osteoblast proliferation and inhibits osteoclast proliferation, and positively affects bone regeneration; however, reports about effects of RAP on bone loss for aged female rats with MEL administration are limited. This study investigated the impact of treatment with RAP on bone loss for aged female rats with MEL administration. Female Sprague-Dawley rats weighing approximately 520â¯g were randomly divided into 3 groups of 10: group CON, group MEL and group MELâ¯+ RAP and received saline, MEL, RAP plus MEL treatment until death at 12 weeks, respectively. The results of maintaining bone mass and bone strength with RAP plus MEL administration were evaluated by histology, microcomputerized tomography (Micro-CT), gene expression analysis and biomechanical testing. Results from this study indicated that MELâ¯+ RAP had stronger effects on the prevention and treatment of osteoporosis than MEL administration. Administration of MELâ¯+ RAP produced the strongest effects on bone parameters and strength for distal femurs and regulation of OPG/RANKL signalling pathway-related gene expression. These results seemed to indicate that RAP could increase the effects of MEL on age-dependent bone loss.
Subject(s)
Melatonin/metabolism , Animals , Bone Density , Bone and Bones , Female , Rats , Rats, Sprague-Dawley , SirolimusABSTRACT
OBJECTIVE: To investigate the relationship between the shape of the lateral wall and the early failure of internal fixation in the fracture of the femoral trochanteric region(FFT). METHODS: Total 295 patients with femoral trochanteric fracture underwent internal fixation from January 2015 to January 2020 were selected. The patients were divided into two groups according to whether there was early internal fixation failure after surgery, 19 patients in the failure group and 276 patients in the normal group. Gender, affected side, age, AO classification, body mass index(BMI), preoperative hemoglobin, X-ray measurement of lower lateral wall thickness, preoperative internal diseases, intraoperative blood loss, postoperative tip apex distance(TAD), postoperative neck shaft angle, operation time and other data were compared between two groups. The shape of the lateral wall was compared between two groups, and the correlation between the shape of the lateral wall and the early internal fixation failure of femoral trochanteric fracture was analyzed. RESULTS: All patients were followed up for more than 1 year. There was no significant difference between two groups in terms of intraoperative blood loss, operation time, postoperative TAD, and postoperative neck shaft angle(P>0.05). At the latest follow-up, the visual anaglue scale (VAS) of the failure group was higher than that of the normal group(P<0.01), and the Harris score of the failure group was lower than that of normal group(P<0.05). The receiver operator characteristic (ROC) curve between shape of lateral wall and failure of early internal fixation of femoral trochanteric fracture was drawn. The critical value of the midpoint lateral wall thickness was 16.5 mm, and the area under the ROC curve was 0.845;The critical value of average sidewall thickness was 16.5 mm, and the area under ROC curve was 0.838;The critical value of the axial area of the sidewall was 7.5 mm, and the area under the ROC curve was 0.826. CONCLUSION: The shape of the lateral femoral wall measured by CT could be used as a predictive factor for the early failure of internal fixation of femoral trochanteric fractures. For patients at risk, more reasonable surgical plans and postoperative preventive measures should be developed.
Subject(s)
Fracture Fixation, Intramedullary , Hip Fractures , Humans , Treatment Outcome , Bone Nails , Retrospective Studies , Hip Fractures/surgery , Fracture Fixation, InternalABSTRACT
The widespread use of therapeutic glucocorticoids has increased the incidences of glucocorticoid-induced osteoporosis (GIOP). Oxidative stress and mitochondrial dysfunction are major causes of GIOP; therefore, alleviation of excess oxidative stress in osteoblasts is a potential therapeutic strategy for osteoporosis. Exosomes derived from ADSCs (ADSCs-Exos), as novel cell-free therapeutics, can modulate various biological processes, such as immunomodulation, reduce oxidative damage, and promote tissue repair as well as regeneration. In this study, ADSCs-Exos restored the viability and osteogenic potential of MC3T3-E1 cells by attenuating apoptosis, oxidative damage, intracellular ROS generation, and mitochondrial dysfunction. Moreover, after pretreatment with ADSCs-Exos, Nrf2 expressions were upregulated in Dex-stimulated osteoblasts. Inhibitory assays showed that silencing Nrf2 partially eliminated the protective effects of ADSCs-Exos. The rat model assays confirmed that ADSCs-Exos alleviated the Dex-induced increase in oxidation levels, restored bone mass of the distal femur, and increased the expressions of Nrf2 and osteogenic markers in bone tissues. Thus, ADSCs-Exos alleviated apoptosis and oxidative stress by regulating Nrf2/HO-1 expressions after Dex and prevented the development of GIOP in vivo.
Subject(s)
Exosomes , Glucocorticoids , Mesenchymal Stem Cells , Osteoporosis , Animals , Rats , Dexamethasone/adverse effects , Exosomes/metabolism , Glucocorticoids/adverse effects , Mesenchymal Stem Cells/metabolism , NF-E2-Related Factor 2/metabolism , Osteoporosis/chemically induced , Osteoporosis/metabolism , Mice , Heme Oxygenase-1ABSTRACT
Oxidative stress is an important contributor to the development of osteoporosis. Melatonin, an indoleamine secreted by the pineal gland, has antioxidant properties. This study aims to explore whether melatonin can promote bone formation and elucidate the mechanisms underlying this process. In this study, we used an in vitro hydrogen peroxide (H2O2)-induced oxidative stress model in MC3T3-E1 cells and an in vivo ovariectomized osteoporotic bone defect model in rats to explore the protective effects of melatonin against osteoporotic bone defects along with the mechanism underlying these effects. We found that melatonin significantly increased alkaline phosphatase activity, mineralization capacity, and the expression of BMP2, RUNX2, and OPN in MC3T3-E1 cells treated with H2O2. Furthermore, melatonin was found to activate SIRT1, SIRT3 and inhibit p66Shc, reduce the intracellular reactive oxygen species levels, stabilize mitochondria, reduce malondialdehyde levels, increase superoxide dismutase activity, and reduce apoptosis in MC3T3-E1 cells treated with H2O2. Intriguingly, these effects could be reversed by the SIRT1 inhibitor EX527. In vivo experiments confirmed that melatonin improves the microstructure and bone mineral density of the distal femoral bone trabecula and promotes bone formation. Meanwhile, melatonin activated SIRT1, inhibited p66Shc and increased SIRT3 expression. Taken together, our findings showed that melatonin can restrain oxidative damage in MC3T3-E1 cells and promote osteogenesis by activating SIRT1 which regulate the activity of SIRT3 and inhibit the expression of p66Shc, suggesting that melatonin could be a potential therapeutic agent for osteoporosis-related bone metabolic diseases.
Subject(s)
Melatonin , Osteoporosis , Sirtuin 3 , Animals , Hydrogen Peroxide/metabolism , Melatonin/pharmacology , Melatonin/therapeutic use , Osteoblasts/metabolism , Osteogenesis , Osteoporosis/chemically induced , Osteoporosis/drug therapy , Osteoporosis/metabolism , Oxidative Stress , Rats , Sirtuin 1/genetics , Sirtuin 1/metabolism , Sirtuin 3/genetics , Sirtuin 3/metabolism , Src Homology 2 Domain-Containing, Transforming Protein 1/metabolism , Src Homology 2 Domain-Containing, Transforming Protein 1/pharmacology , Src Homology 2 Domain-Containing, Transforming Protein 1/therapeutic useABSTRACT
OBJECTIVE: To measure the maximum corridor parameters of the infra acetabular screw and evaluate the feasibility of screw insertion through digital analysis of the acetabular structure. METHODS: The pelvic CT data of 100 patients who received plain pelvic CT scan from April 2013 to June 2015 were retrospectively analyzed. There were 50 males, aged 20 to 84 years, with an average age of (48.42±17.48) years, and 50 females, aged 18 to 87 years, with an average age of (55.02±19.54) years. Patients with acetabular fractures, hip dysplasia, and metal implants in the acetabulum were excluded. Import CT data into Mimics software in DICOM format to generate a three-dimensional model, and find the axialprojection of the infra-acetabular corridor in the middle of the pubis ramus in the inlet view. A virtual screw was placed in the infra-acetabular space and measure the parameters including the diameter and the length of the maximum corridor, the distance from the insertion point to the pubic symphysis, to the anterosuperior iliac spine and to the medial edge of the pelvis. Then import the pelvic model into 3- matic software, establish the pelvic model anterior pelvic plane and median sagittal plane, and measure the angle between the screw axis and the two planes. A minimum corridor diameter of at least 5 mm was defined as a cutoff for placing a 3.5 mm screw, and calculate the screw insertion rate. RESULTS: In 100 cases, 49% of patients had a infra acetabular corridor with a diameter ≥5 mm, and the rate of screw placement in men was significantly higher than that in women. The average diameter of the maximum corridor of infra-acetabular screw was (4.86±1.72) mm, the average length was (94.04±8.29) mm, the average distance from the insertion point to the pubic symphysis was (60.92±4.84) mm, to the anterosuperior iliac spine was (85.15± 6.85) mm, and to the medial edge of the pelvis was (6.12±3.32) mm. The mean angle between the axis of the screw and the median sagittal plane was (-1.38±4.74)°, and the mean angle between the axis of the screw and the anterior pelvic plane was (56.77±7.93)°. There are significant differences between male and female measured parameters, except for the angle between the screw axis and the anterior pelvic plane. There was no statistically significant difference in the maximum corridor parameters of infra-acetabular screw on both sides of the pelvis. CONCLUSION: This study shows that the insertion rate of infra-acetabular screws is low in local patients, and the feasibility of screw insertion should be fully evaluated before surgery.