Objective To observe the effects of Zhuang Gu Zhi Tong Formula (ZGZTF) on antagonist SOST in canonical Wnt/β-catenin signaling pathway in osteoporosis. Methods We analyzed the differential genes of patients with oste...Objective To observe the effects of Zhuang Gu Zhi Tong Formula (ZGZTF) on antagonist SOST in canonical Wnt/β-catenin signaling pathway in osteoporosis. Methods We analyzed the differential genes of patients with osteoporosis and normal subjects from the GEO database and then found SOST with specific expression. We analyzed SOST as an antagonist of the Wnt signaling pathway by the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Then we studied the effect of ZGZTF on SOST in Wnt signaling pathway. Osteoporosis model was induced by ovariectomy (OVX) in 8-week-old female Sprague–Dawley (SD) rats. After 12 weeks of treatment with ZGZTF by intragastric administration, the rats were put to death in batch. The changes of alkaline phosphatase (ALP), bone gla protein (BGP) and estradiol (E2) in serum were determined, and bone mineral density (BMD) and histomorphology of right femur were observed. Biomechanics of lumbar vertebra were measured, and the expression of SOST, Wnt3a,β-catenin, LRP5, Runx2, Osx and their mRNA involving the canonical Wnt/β-catenin signaling pathway were detected by Western blot, RT-PCR and Immunohistochemical analysis. All data were analyzed by SPSS 22.0. Results Twelve weeks of treatment with ZGZTF could significantly decrease the level of ALP and BGP in serum, increase the BMD of femurs, and improve the biomechanical capability of vertebral body in maximum loading and elastic modulus. Concerning histomorphology, we found ordered arrangement of trabeculae, slightly thinning of trabeculae and none obvious slight fractures in femurs after 12 weeks of treatment with ZGZTF. The expression of LRP5,β-catenin, Runx2 and Osx involved in the canonical Wnt/β-catenin signaling pathway was significantly up-regulated in the presence of ZGZTF,and the expression of SOST in this pathway was down-regulated. Conclusions These results suggest that ZGZTF may be antiosteoporosis by down-regulating SOST protein to promote Wnt/β-catenin signaling pathway.展开更多
Low bone mineral density and the increased risk of fracture in gastrointestinal diseases have a multifactorial pathogenesis. Inflammatory bowel disease （IBD） has been associated with an increased risk of osteoporosi...Low bone mineral density and the increased risk of fracture in gastrointestinal diseases have a multifactorial pathogenesis. Inflammatory bowel disease （IBD） has been associated with an increased risk of osteoporosis and osteopenia and epidemiologic studies have reported an increased prevalence of low bone mass in patients with IBD. Certainly, genetics play an important role, along with other factors such as systemic inflammation, malnutrition, hypogonadism, glucocorticoid therapy in IBD and other lifestyle factors. At a molecular level the proinflammatory cytokines that contribute to the intestinal immune response in IBD are known to enhance bone resorption. There are genes influencing osteoblast function and it is likely that LRP5 may be involved in the skeletal development. Also the identification of vitamin D receptors （VDRs） and some of its polymorphisms have led to consider the possible relationships between them and some autoimmune diseases and may be involved in the pathogenesis through the exertion of its immunomodulatory effects during inflammation. Trying to explain the physiopathology we have found that there is increasing evidence for the integration between systemic inflammation and bone loss likely mediated via receptor for activated nuclear factor kappa-B （RANK）, RANK-ligand, and osteoprotegerin, proteins that can affect both osteoclastogenesis and T-cell activation. Although glucocorticoids can reduce mucosal and systemic inflammation, they have intrinsic qualities that negatively impact on bone mass. It is still controversial if all IBD patients should be screened, especially in patients with preexisting risk factors for bone disease. Available methods to measure BMD include single energy x-ray absorptiometry, DXA, quantitative computed tomography （QCT）, radiographic absorptiometry, and ultrasound.DXA is the establish method to determine BMD, and routinely is measured in the hip and the lumbar spine. There are several treatments options that have proven their effectiveness, while new emergent therapies such as calcitonin and teriparatide among others remain to be assessed.展开更多
Objective： To observe the clinical result and assess clinical value of cemented bipolar hemiarthroplasty with a novel cerclage cable technique for treatment of unstable intertrochanteric hip fractures in senile patie...Objective： To observe the clinical result and assess clinical value of cemented bipolar hemiarthroplasty with a novel cerclage cable technique for treatment of unstable intertrochanteric hip fractures in senile patients. Methods： Forty-eight consecutive patients with unstable intertrochanteric fractures were treated in our hospital from March 2001 to March 2006 （ Evans type Ⅲ in 11 cases, Evans type Ⅳ in 25 cases and Evans type Ⅴ in 22 cases）. All the cases were evaluated by Zuckerman functional recovery score （ FRS ） and operative risk assessment software 1 （ORAS1）, which were based on the patients ＇ physical and laboratory examinations preoperatively. Seventeen cases （19 hips） were treated with cemented bipolar hemiarthroplasty. There were 5 male cases （5 hips） and 12 female cases （14 hips, including 2 patients who suffered from additional slight injuries and resulted in contralateral hip fracture and were treated with the same procedure 3 months after the first operation ）. The average age was 85 years （78-95 years ）. All the operations were carried out under general anesthesia, through Southern incision and lateral approach by the same orthopaedic surgeon. All prostheses consisted of Link SPH femoral stem and bipolar femoral head. All patients were followed up for more than 30 days. Results ： The operative risks of all the 17 cases （ 19 hips） were calculated by ORAS1 preoperatively. The average preoperative FRS was 81.7 （ 80. 7- 82.7 ）. The average predictive value of operative morbidity was 10% （7 %-15 % ）. The average predictive value of mortality was 2.97 % （ 2. 1%-3.2 % ）. The average operation time was 1.5 hours. The average blood transfusion was 400 nd. There were no operative or anesthetic complications and no deaths within 30 days after operation. Sitting up was permitted 3 to 4 days after operation, and partial weight bearing was permitted 5 to 7 days after operation. Patients were allowed to walk with a walker 10 days after operation. The average FRS was 78.7 at 30 days postoperatively. No patient died during at least one year follow-up. Conclusions Although the value of the technique of cemented bipolar hemiarthroplasty in the treatment of unstable intertrochanteric hip fracture is not widely recognized, we have consistently achieved satisfactory results with strict preoperative risk assessment, strict indication selection and systematic postoperative rehabilitation.展开更多
基金the funding support from the National Natural Science Foundation of China (No. 81573956)Natural Science Foundation of Hunan Province (No. 2018JJ2297)+3 种基金Key Program of Chinese Medicine Science Research Plan of Hunan Province (No. 201612)Key Program of Scientific Research Fund of Hunan Provincial Education Department (No. 16A162)National College Students Innovation and Entrepreneurship Project (No. 201710541002)The Project of Research Learning and Innovative Experiment for College Students in Hunan (No. 2015217, No. 2015220, No. 2016284 and No. 2016281)
文摘Objective To observe the effects of Zhuang Gu Zhi Tong Formula (ZGZTF) on antagonist SOST in canonical Wnt/β-catenin signaling pathway in osteoporosis. Methods We analyzed the differential genes of patients with osteoporosis and normal subjects from the GEO database and then found SOST with specific expression. We analyzed SOST as an antagonist of the Wnt signaling pathway by the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Then we studied the effect of ZGZTF on SOST in Wnt signaling pathway. Osteoporosis model was induced by ovariectomy (OVX) in 8-week-old female Sprague–Dawley (SD) rats. After 12 weeks of treatment with ZGZTF by intragastric administration, the rats were put to death in batch. The changes of alkaline phosphatase (ALP), bone gla protein (BGP) and estradiol (E2) in serum were determined, and bone mineral density (BMD) and histomorphology of right femur were observed. Biomechanics of lumbar vertebra were measured, and the expression of SOST, Wnt3a,β-catenin, LRP5, Runx2, Osx and their mRNA involving the canonical Wnt/β-catenin signaling pathway were detected by Western blot, RT-PCR and Immunohistochemical analysis. All data were analyzed by SPSS 22.0. Results Twelve weeks of treatment with ZGZTF could significantly decrease the level of ALP and BGP in serum, increase the BMD of femurs, and improve the biomechanical capability of vertebral body in maximum loading and elastic modulus. Concerning histomorphology, we found ordered arrangement of trabeculae, slightly thinning of trabeculae and none obvious slight fractures in femurs after 12 weeks of treatment with ZGZTF. The expression of LRP5,β-catenin, Runx2 and Osx involved in the canonical Wnt/β-catenin signaling pathway was significantly up-regulated in the presence of ZGZTF,and the expression of SOST in this pathway was down-regulated. Conclusions These results suggest that ZGZTF may be antiosteoporosis by down-regulating SOST protein to promote Wnt/β-catenin signaling pathway.
文摘Low bone mineral density and the increased risk of fracture in gastrointestinal diseases have a multifactorial pathogenesis. Inflammatory bowel disease （IBD） has been associated with an increased risk of osteoporosis and osteopenia and epidemiologic studies have reported an increased prevalence of low bone mass in patients with IBD. Certainly, genetics play an important role, along with other factors such as systemic inflammation, malnutrition, hypogonadism, glucocorticoid therapy in IBD and other lifestyle factors. At a molecular level the proinflammatory cytokines that contribute to the intestinal immune response in IBD are known to enhance bone resorption. There are genes influencing osteoblast function and it is likely that LRP5 may be involved in the skeletal development. Also the identification of vitamin D receptors （VDRs） and some of its polymorphisms have led to consider the possible relationships between them and some autoimmune diseases and may be involved in the pathogenesis through the exertion of its immunomodulatory effects during inflammation. Trying to explain the physiopathology we have found that there is increasing evidence for the integration between systemic inflammation and bone loss likely mediated via receptor for activated nuclear factor kappa-B （RANK）, RANK-ligand, and osteoprotegerin, proteins that can affect both osteoclastogenesis and T-cell activation. Although glucocorticoids can reduce mucosal and systemic inflammation, they have intrinsic qualities that negatively impact on bone mass. It is still controversial if all IBD patients should be screened, especially in patients with preexisting risk factors for bone disease. Available methods to measure BMD include single energy x-ray absorptiometry, DXA, quantitative computed tomography （QCT）, radiographic absorptiometry, and ultrasound.DXA is the establish method to determine BMD, and routinely is measured in the hip and the lumbar spine. There are several treatments options that have proven their effectiveness, while new emergent therapies such as calcitonin and teriparatide among others remain to be assessed.
文摘Objective： To observe the clinical result and assess clinical value of cemented bipolar hemiarthroplasty with a novel cerclage cable technique for treatment of unstable intertrochanteric hip fractures in senile patients. Methods： Forty-eight consecutive patients with unstable intertrochanteric fractures were treated in our hospital from March 2001 to March 2006 （ Evans type Ⅲ in 11 cases, Evans type Ⅳ in 25 cases and Evans type Ⅴ in 22 cases）. All the cases were evaluated by Zuckerman functional recovery score （ FRS ） and operative risk assessment software 1 （ORAS1）, which were based on the patients ＇ physical and laboratory examinations preoperatively. Seventeen cases （19 hips） were treated with cemented bipolar hemiarthroplasty. There were 5 male cases （5 hips） and 12 female cases （14 hips, including 2 patients who suffered from additional slight injuries and resulted in contralateral hip fracture and were treated with the same procedure 3 months after the first operation ）. The average age was 85 years （78-95 years ）. All the operations were carried out under general anesthesia, through Southern incision and lateral approach by the same orthopaedic surgeon. All prostheses consisted of Link SPH femoral stem and bipolar femoral head. All patients were followed up for more than 30 days. Results ： The operative risks of all the 17 cases （ 19 hips） were calculated by ORAS1 preoperatively. The average preoperative FRS was 81.7 （ 80. 7- 82.7 ）. The average predictive value of operative morbidity was 10% （7 %-15 % ）. The average predictive value of mortality was 2.97 % （ 2. 1%-3.2 % ）. The average operation time was 1.5 hours. The average blood transfusion was 400 nd. There were no operative or anesthetic complications and no deaths within 30 days after operation. Sitting up was permitted 3 to 4 days after operation, and partial weight bearing was permitted 5 to 7 days after operation. Patients were allowed to walk with a walker 10 days after operation. The average FRS was 78.7 at 30 days postoperatively. No patient died during at least one year follow-up. Conclusions Although the value of the technique of cemented bipolar hemiarthroplasty in the treatment of unstable intertrochanteric hip fracture is not widely recognized, we have consistently achieved satisfactory results with strict preoperative risk assessment, strict indication selection and systematic postoperative rehabilitation.
