Objective:To evaluate the effect of human umbilical cord mesenchymal stem cells(hUC-MSCs)on preventing rats from glucocorticoid-induced osteonecrosis of femoral head(GC-ONFH)in the early stage in vivo and to investiga...Objective:To evaluate the effect of human umbilical cord mesenchymal stem cells(hUC-MSCs)on preventing rats from glucocorticoid-induced osteonecrosis of femoral head(GC-ONFH)in the early stage in vivo and to investigate the possible mechanism of hUC-MSCs in regulating the balance of osteogenesis and adipogenesis.Methods:All rats were randomly divided into 3 groups:control group(C group),model group(M group),and intervention group(Ⅰ group).The model of GC-ONFH was developed by a sequential administration of lipopolysaccharide and methylprednisolone.The rats in the Ⅰ group were treated with caudal vein injection of hUC-MSCs.Six weeks later,the blood samples were obtained to measure the activity of alkaline phosphatase(ALP)and the content of triglyceride(TG)in serum,and the femoral heads were harvested and observed by hematoxylin-eosin staining,Micro-CT,Western blot and real-time quantitative polymerase chain reaction.Results:After intervention of hUC-MSCs,the necrosis rate of femoral head decreased from 83%(10/12)to 33%(4/12),the rate of empty bone lacuna was significantly decreased,the activity of ALP increased significantly,the content of TG decreased significantly,the bone density increased obviously,the expression of RUNX2 and Col Ⅰ increased significantly and the expression of PPARγ decreased significantly.Conclusion:These results revealed that caudal vein injection of hUC-MSCs can effectively reduce the incidence of GC-ONFH in rats by increasing ALP activity and reducing TG content in serum,increasing bone mineral density,promoting the expression of RUNX2 and Col I,and inhibiting the expression of PPARγ.展开更多
Objective: To study the relationships among magnetic resonance imaging (MRI), histological findings, and insu- lin-like growth factor-I (IGF-I) in steroid-induced osteonecrosis of the femoral head in rabbits. Methods:...Objective: To study the relationships among magnetic resonance imaging (MRI), histological findings, and insu- lin-like growth factor-I (IGF-I) in steroid-induced osteonecrosis of the femoral head in rabbits. Methods: Thirty rabbits were randomly divided into experimental Group A (n=15) and control Group B (n=15). The 7.5 mg/kg (2 ml) of dexamethasone (DEX) and physiological saline (2 ml) were injected into the right gluteus medius muscle twice at one-week intervals in animals of Groups A and B, respectively. At 4, 8 and 16 weeks after obtaining an MRI, the rabbits were sacrificed and the femoral head from one side was removed for histological study of lacunae empty of osteocytes, subchondral vessels, and size of fat cells under microscopy, and the femoral head from the other side was removed for enzyme-linked immunoadsorbent assay (ELISA) for IGF-I. Results: At 4, 8 and 16 weeks after treatment, no necrotic lesions were detected in Group B, while they were detected in Group A. Light microscopy revealed that the fat cells of the marrow cavity were enlarged, subchondral vessels were evidently decreased, and empty bone lacunae were clearly increased. The IGF-I levels in Group A were significantly higher than those in Group B. At 8 weeks after the DEX injection, the MRI of all 20 femora showed an inhomogeneous, low signal intensity area in the femoral head, and at 16 weeks, the findings of all 10 femora showed a specific "line-like sign". The MRI findings of all femora in Group B were normal. Conclusion: MRI is a highly sensitive means of diagnosing early experimental osteonecrosis of the femoral head. However, the abnormal marrow tissues appeared later than 4 weeks when the expression of IGF-I increased. This reparative factor has an early and important role in response to steroid-induced osteonecrosis of the femoral head, and provides a theoretical foundation for understanding the pathology and designing new therapies.展开更多
目的观察祛痰通络方联合依降钙素治疗早中期非创伤性股骨头坏死(Non-traumatic osteonecrosis of the femoral head,NONFH)的临床疗效。方法选取2016年5月—2017年6月期间上海中医药大学附属岳阳医院收治的早中期非创伤性股骨头坏死患...目的观察祛痰通络方联合依降钙素治疗早中期非创伤性股骨头坏死(Non-traumatic osteonecrosis of the femoral head,NONFH)的临床疗效。方法选取2016年5月—2017年6月期间上海中医药大学附属岳阳医院收治的早中期非创伤性股骨头坏死患者72例,按照1∶1比例随机分组,对照组36例采用西医治疗联合仙灵骨葆胶囊治疗,治疗组36例采用西医治疗联合祛痰通络方治疗,两组均治疗3个疗程,共计9个月,并评价其不同时期的中医证候得分、实验室指标、Harris评分及影像学变化。结果两组患者在治疗3个疗程后的中医证候评分治疗组均低于对照组(P<0.05)。Harris评分治疗组均高于对照组,差异有统计学意义(P<0.05);组内比较,两组治疗后评分均高于治疗前,差异有统计学意义(P<0.05)。在治疗9个月后,两组影像学变化比较,治疗组有效率77.78%(28/36)高于对照组有效率55.56%(20/36),差异有统计学意义(P<0.05)。结论祛痰通络方治疗早中期非创伤性股骨头坏死疗效确切,值得临床参考并进一步推广。展开更多
OBJECTIVE: To investigate the effects of HuoguⅠformula on regulation of lipid metabolism in steroid-induced osteonecrosis of the femoral head(SONFH) rats and verify our hypothesis that HuoguⅠ formula regulates lipid...OBJECTIVE: To investigate the effects of HuoguⅠformula on regulation of lipid metabolism in steroid-induced osteonecrosis of the femoral head(SONFH) rats and verify our hypothesis that HuoguⅠ formula regulates lipid metabolism by down-regulating peroxisome proliferator-activated receptor gamma(PPARγ) expression and activating Wnt signaling pathways.METHODS: Eighty-five rats were divided into four groups: control, model, Huogu 15 g/kg and Huogu30 g/kg. Six weeks later, animals were anaesthetized, femora were dissected for histopathological examination of the osteonecrotic changes and repair processes, micro computed tomography(Micro-CT)-based micro-angiography was performed to assess vascularization. Serum lipid levels were detected by haematological examination. The expressions of PPARγ, Wnt3a, low density lipoprotein receptor-related protein 5(LRP5) and β-catenin were evaluated by immunohistochemistry,Western blot and quantitative real-time polymerase chain reaction analyses.RESULTS: The incidence of osteonecrosis, ratio of empty lacuna, adipose tissue area and adipocyte perimeter in the bone marrow were dramatically lower in the Huogu Ⅰ formula treatment groups.Bymicro-CTquantification,HuoguⅠformulatreatment dose-dependently increased vessel volume,vessel surface, percentage of vessel volume and vessel thickness of the femoral heads of SONFH rats. Levels of serum lipid in Huogu 15 g/kg and Huogu 30 g/kg groups reduced significantly.HuoguⅠformula treatment could suppress the expression of PPARγ and increase the expressions of Wnt3a, LRP5 and β-catenin at both protein and mRNA levels.CONCLUSION: The results of our present study highlight the lipid-lowering potential of Huogu Ⅰformula, and provide further evidence of the involvement of the PPARγ inhibition and Wnt/LRP5/β-catenin signaling activation in the effects of HuoguⅠformula.展开更多
基金supported by the National Natural Science Foundation of China(No.81672154).
文摘Objective:To evaluate the effect of human umbilical cord mesenchymal stem cells(hUC-MSCs)on preventing rats from glucocorticoid-induced osteonecrosis of femoral head(GC-ONFH)in the early stage in vivo and to investigate the possible mechanism of hUC-MSCs in regulating the balance of osteogenesis and adipogenesis.Methods:All rats were randomly divided into 3 groups:control group(C group),model group(M group),and intervention group(Ⅰ group).The model of GC-ONFH was developed by a sequential administration of lipopolysaccharide and methylprednisolone.The rats in the Ⅰ group were treated with caudal vein injection of hUC-MSCs.Six weeks later,the blood samples were obtained to measure the activity of alkaline phosphatase(ALP)and the content of triglyceride(TG)in serum,and the femoral heads were harvested and observed by hematoxylin-eosin staining,Micro-CT,Western blot and real-time quantitative polymerase chain reaction.Results:After intervention of hUC-MSCs,the necrosis rate of femoral head decreased from 83%(10/12)to 33%(4/12),the rate of empty bone lacuna was significantly decreased,the activity of ALP increased significantly,the content of TG decreased significantly,the bone density increased obviously,the expression of RUNX2 and Col Ⅰ increased significantly and the expression of PPARγ decreased significantly.Conclusion:These results revealed that caudal vein injection of hUC-MSCs can effectively reduce the incidence of GC-ONFH in rats by increasing ALP activity and reducing TG content in serum,increasing bone mineral density,promoting the expression of RUNX2 and Col I,and inhibiting the expression of PPARγ.
基金Project (No. 06MA169) supported by the Medical Science Founda-tion of Nanjing Military Region, China
文摘Objective: To study the relationships among magnetic resonance imaging (MRI), histological findings, and insu- lin-like growth factor-I (IGF-I) in steroid-induced osteonecrosis of the femoral head in rabbits. Methods: Thirty rabbits were randomly divided into experimental Group A (n=15) and control Group B (n=15). The 7.5 mg/kg (2 ml) of dexamethasone (DEX) and physiological saline (2 ml) were injected into the right gluteus medius muscle twice at one-week intervals in animals of Groups A and B, respectively. At 4, 8 and 16 weeks after obtaining an MRI, the rabbits were sacrificed and the femoral head from one side was removed for histological study of lacunae empty of osteocytes, subchondral vessels, and size of fat cells under microscopy, and the femoral head from the other side was removed for enzyme-linked immunoadsorbent assay (ELISA) for IGF-I. Results: At 4, 8 and 16 weeks after treatment, no necrotic lesions were detected in Group B, while they were detected in Group A. Light microscopy revealed that the fat cells of the marrow cavity were enlarged, subchondral vessels were evidently decreased, and empty bone lacunae were clearly increased. The IGF-I levels in Group A were significantly higher than those in Group B. At 8 weeks after the DEX injection, the MRI of all 20 femora showed an inhomogeneous, low signal intensity area in the femoral head, and at 16 weeks, the findings of all 10 femora showed a specific "line-like sign". The MRI findings of all femora in Group B were normal. Conclusion: MRI is a highly sensitive means of diagnosing early experimental osteonecrosis of the femoral head. However, the abnormal marrow tissues appeared later than 4 weeks when the expression of IGF-I increased. This reparative factor has an early and important role in response to steroid-induced osteonecrosis of the femoral head, and provides a theoretical foundation for understanding the pathology and designing new therapies.
文摘目的观察祛痰通络方联合依降钙素治疗早中期非创伤性股骨头坏死(Non-traumatic osteonecrosis of the femoral head,NONFH)的临床疗效。方法选取2016年5月—2017年6月期间上海中医药大学附属岳阳医院收治的早中期非创伤性股骨头坏死患者72例,按照1∶1比例随机分组,对照组36例采用西医治疗联合仙灵骨葆胶囊治疗,治疗组36例采用西医治疗联合祛痰通络方治疗,两组均治疗3个疗程,共计9个月,并评价其不同时期的中医证候得分、实验室指标、Harris评分及影像学变化。结果两组患者在治疗3个疗程后的中医证候评分治疗组均低于对照组(P<0.05)。Harris评分治疗组均高于对照组,差异有统计学意义(P<0.05);组内比较,两组治疗后评分均高于治疗前,差异有统计学意义(P<0.05)。在治疗9个月后,两组影像学变化比较,治疗组有效率77.78%(28/36)高于对照组有效率55.56%(20/36),差异有统计学意义(P<0.05)。结论祛痰通络方治疗早中期非创伤性股骨头坏死疗效确切,值得临床参考并进一步推广。
基金Supported by the National Natural Science Foundation ofChina(No.81173417No.30901982No.81373656)
文摘OBJECTIVE: To investigate the effects of HuoguⅠformula on regulation of lipid metabolism in steroid-induced osteonecrosis of the femoral head(SONFH) rats and verify our hypothesis that HuoguⅠ formula regulates lipid metabolism by down-regulating peroxisome proliferator-activated receptor gamma(PPARγ) expression and activating Wnt signaling pathways.METHODS: Eighty-five rats were divided into four groups: control, model, Huogu 15 g/kg and Huogu30 g/kg. Six weeks later, animals were anaesthetized, femora were dissected for histopathological examination of the osteonecrotic changes and repair processes, micro computed tomography(Micro-CT)-based micro-angiography was performed to assess vascularization. Serum lipid levels were detected by haematological examination. The expressions of PPARγ, Wnt3a, low density lipoprotein receptor-related protein 5(LRP5) and β-catenin were evaluated by immunohistochemistry,Western blot and quantitative real-time polymerase chain reaction analyses.RESULTS: The incidence of osteonecrosis, ratio of empty lacuna, adipose tissue area and adipocyte perimeter in the bone marrow were dramatically lower in the Huogu Ⅰ formula treatment groups.Bymicro-CTquantification,HuoguⅠformulatreatment dose-dependently increased vessel volume,vessel surface, percentage of vessel volume and vessel thickness of the femoral heads of SONFH rats. Levels of serum lipid in Huogu 15 g/kg and Huogu 30 g/kg groups reduced significantly.HuoguⅠformula treatment could suppress the expression of PPARγ and increase the expressions of Wnt3a, LRP5 and β-catenin at both protein and mRNA levels.CONCLUSION: The results of our present study highlight the lipid-lowering potential of Huogu Ⅰformula, and provide further evidence of the involvement of the PPARγ inhibition and Wnt/LRP5/β-catenin signaling activation in the effects of HuoguⅠformula.
