RESUMEN
Aging drives the accumulation of senescent cells (SnCs) by secreting factors that cause the senescence-associated secretory phenotype (SASP), including stem cells in the bone marrow, which contribute to aging-related bone degradation. Osteoarthritis (OA) is a serious chronic injury disease, and increasing age is a major risk factor. The accumulation of SnCs may accelerate the development of OA, and the accumulation of SnCs may benefit from its resistance to apoptotic stimuli. Therefore, local elimination of SnCs could be a promising treatment for OA. Apoptosis inhibitor protein (IAP) is an important antiapoptotic protein in vivo. AT-406 is a small molecule inhibitor of the IAP genes and also regulates the transcription of several genes. Here, we show that SnCs upregulate the antiapoptotic proteins c-IAP1, c-IAP2 and XIAP.The combined inhibition of c-IAP1, c-IAP2 and XIAP using siRNA or AT-406 specifically induce the apoptosis of SnCs.In addition, XIAP and STX17 bind to each other to regulate the fusion of autophagosomes and lysosomes in SnCs, which in turn, affects the fate of SnCs. It is worth noting that the clearance of SnCs attenuated the secretion of SASP and created a proregenerative environment. Most importantly, local clearance of SnCs significantly attenuated the progression of osteoarthritis in rats without significant toxic effects. Thus, local elimination of SnCs may be a potential treatment for OA. This is the first report of inhibition of IAPs for clearing SnCs and suggests that eradication of SnCs may be a new strategy for the treatment of age-related diseases.
Asunto(s)
Senescencia Celular/fisiología , Proteínas Inhibidoras de la Apoptosis/metabolismo , Osteoartritis/metabolismo , Animales , Apoptosis , Autofagosomas , Autofagia , Azocinas/antagonistas & inhibidores , Compuestos de Bencidrilo/antagonistas & inhibidores , Ciclo Celular , Proliferación Celular , Modelos Animales de Enfermedad , Regulación de la Expresión Génica , Proteínas Inhibidoras de la Apoptosis/genética , Lisosomas , Osteoartritis/patología , Proteínas Qa-SNARE/metabolismo , Ratas , Ratas Sprague-Dawley , Factores de RiesgoRESUMEN
Periarticular fracture of the shoulder is a common type of fractures in the elderly. Postoperative adverse events such as internal fixation failure, humeral head ischemic necrosis and upper limb dysfunction occur frequently, which seriously endangers the exercise and health of the elderly. Compared with the fracture with normal bone mass, the osteoporotic periarticular fracture of the shoulder is complicated with slow healing and poor rehabilitation, so the clinical management becomes more difficult. At present, there is no targeted guideline or consensus for this type of fracture in China. In such context, experts from Youth Osteoporosis Group of Chinese Orthopedic Association, Orthopedic Expert Committee of Geriatrics Branch of Chinese Association of Gerontology and Geriatrics, Osteoporosis Group of Youth Committee of Chinese Association of Orthopedic Surgeons and Osteoporosis Committee of Shanghai Association of Chinese Integrative Medicine developed the Chinese expert consensus on the diagnosis and treatment of osteoporotic periarticular fracture of the shoulder in the elderly ( version 2023). Nine recommendations were put forward from the aspects of diagnosis, treatment strategies and rehabilitation of osteoporotic periarticular fracture of the shoulder, hoping to promote the standardized, systematic and personalized diagnosis and treatment concept and improve functional outcomes and quality of life in elderly patients with osteoporotic periarticular fracture of the shoulder.
RESUMEN
BACKGROUND:Steroid-induced osteonecrosis of the femoral head (SONFH) is a common bone disease characterized as high morbidity and poor prognosis,but the pathogenesis is unclear.Oxidative stress treatment is closely related to the occurrence and development of SONFH,and has tremendous potential in the treatment of SONFH,which can be realized by Nano-Se.OBJECTIVE:To observe the protective effect of porous Se@SiO2 nanocomposite on chondrocytes by antioxidant stress,and to further explore its mechanism of protection and treatment of SONFH.METHODS:(1) In vitro experiment:The rat chondrocytes were isolated,cultured and identified.Then,the chondrocytes were cultured with porous Se@SiO2 nanocomposite to suppress the production of reactive oxygen species (ROS).(2) In vivo experiment:A total of 36 rats were randomly divided into three groups.Steroid-induced group and experimental group were treated with intraperitoneal injection of lipopolysaccharide and intramuscular injection of methylprednisolone to induce SON FH models.Seven days after modeling,the experimental group was intraperitoneally injected with porous Se@SiO2 nanocomposite.No intervention was done in control group (blank control).At 8 weeks after modeling,rat bilateral femoral heads were taken for hematoxylin-eosin staining and Micro-CT scanning.RESULTS AND CONCLUSION:Results from the ROS detection and TUNEL apoptosis tests showed that the level of ROS in the chondrocytes was significantly reduced after intervention with Se@SiO2 (P < 0.05).Micro-CT scanning findings showed that the bone mineral density,bone volume,bone area/bone volume,trabecular number,trabecular thickness,and trabecular separation in the steroid-induced and experimental groups were significantly different from those in the control group (P < 0.05).Hematoxylin-eosin staining results showed smooth femoral head,normal bone cells,chondrocytes and trabecular bone,as well as few empty bone lacunae and fat cells in the control group,while in the steroid-induced group,there was bone trabecular fracture,fat cell hypertrophy fusion,a large number of empty bone lacunae and obvious osteonecrosis.These manifestations were significantly improved in the experimental group.To conclude,the porous Se@SiO2 nanocomposite has good antioxidative stress ability,suppresses the ROS production and exerts therapeutic effects on SONFH.
RESUMEN
Objective To explore the operative techniques for AO/OTA type 31-A3.1 and 31-A3.2 intertrochanteric fractures fixed with intrameduallary nail.Methods Seventy-four cases of unstable intertrochanteric fracture (AO/OTA type 31-A3.1 and 31-A3.2) from January 2007 to December 2010 were analyzed retrospectively.There were 33 males and 41 females,aged from 36-87 years (mean,71 years).The right hip was involved in 34 patients and the left in 40 patients.The mechanism of injury was traffic injuries in 27 cases,fall damage in 43 cases,injury by falling in 3 case and crush injury in 6 cases.Percutaneous joystick technique,Homann retractor technique,clamp technique and mini-incision was applied to aid reduction during the surgery.All cases were fixed with proximal intrameduallary nail.Clinical and radiographic outcomes were recorded.The postoperative hip function was evaluated using Harris score.Results With the aid of C-arm,closed reduction was performed in 73 cases.Only one patient experienced open reduction because of failure of closed reduction.Sixty-five cases were followed up for 8 to 23 months (mean,14.5 months).Bone union was observed in all cases with the average time of 7.4 months (range,8-23).The operation time,blood loss,the frequency of X-ray exposure was 75±4 minutes,135±5 ml and 24±3 times,respectively.At final follow-up,29 cases were classified as excellent,31 as good,and 5 as fair.The mean Harris hip score was 91.4 points (range,87-95).The overall rate of excellent or good result was 92.3%.Conclusion It is difficult to perform close reduction for unstable intertrochanteric hip fracture (AO/OTA type 31-A3.1and 31-A3.2),especially in relatively young patients.Special operative skills are necessary in some cases.
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[Objective]To understand the changes of periprosthetic bone mineral density(BMD) of the proximal femur in patients with failed hip arthroplasty by measuring with dual energy X-ray absorptiometry(DEXA). [Method]Periprosthetic BMD was determined in 9 patients with revision total hip arthroplasty by dual energy X-ray absorptiometry(DEXA),defining regions of interest according to Gruen(1~7),and comparing the operation side with the nonoperation side.Clinic results of the cases were evaluated according to Harris Hip Score(HHS).[Result]The mean HHS was 61 points in 9 patients at this follow-up examination.There was a significant decrease(8.9%~27.6 %) in BMD in every Gruen zone as compared with the nonoperation side.[Conclusion]The bone loss in the proximal femur in patients with failed hip arthroplasty is significant,and the pattern of bone loss around failed hip arthroplasty may be different from the typical remodeling seen after successful hip arthroplasty.