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
It is estimated that 20000 to 30000 new patients are diagnosed with osteonecrosis annually accounting for approximately 10% of the 250000 total hip arthroplasties done annually in the United States. Thelack of level 1...It is estimated that 20000 to 30000 new patients are diagnosed with osteonecrosis annually accounting for approximately 10% of the 250000 total hip arthroplasties done annually in the United States. Thelack of level 1 evidence in the literature makes it difficult to identify optimal treatment protocols to manage patients with pre-collapse avascular necrosis of the femoral head, and early intervention prior to collapse is critical to successful outcomes in joint preserving procedures. There have been a variety of traumatic and atraumatic factors that have been identified as risk factors for osteonecrosis, but the etiology and pathogenesis still remains unclear. Current osteonecrosis diagnosis is dependent upon plain anteroposterior and frog-leg lateral radiographs of the hip, followed by magnetic resonance imaging(MRI). Generally, the first radiographic changes seen by radiograph will be cystic and sclerotic changes in the femoral head. Although the diagnosis may be made by radiograph, plain radiographs are generally insufficient for early diagnosis, therefore MRI is considered the most accurate benchmark. Treatment options include pharmacologic agents such as bisphosphonates and statins, biophysical treatments, as well as joint-preserving and joint-replacing surgeries. the surgical treatment of osteonecrosis of the femoral head can be divided into two major branches: femoral head sparing procedures(FHSP) and femoral head replacement procedures(FHRP). In general, FHSP are indicated at pre-collapse stages with minimal symptoms whereas FHRP are preferred at post-collapse symptomatic stages. It is difficult to know whether any treatment modality changes the natural history of core decompression since the true natural history of core decompression has not been delineated.展开更多
Objective To review the recent developments in the mechanisms of glucocorticoids induced osteonecrosis of femoral head （ONFH） and introduce a new theory of ONFH.Data sources Both Chinese- and English-language litera...Objective To review the recent developments in the mechanisms of glucocorticoids induced osteonecrosis of femoral head （ONFH） and introduce a new theory of ONFH.Data sources Both Chinese- and English-language literatures were searched using MEDLINE （1997-2011）,Pubmed （1997-2011 ） and the Index of Chinese-language Literature （1997-2011 ）.Study selection Data from published articles about mechanisms of glucocorticoids induced ONFH in recent domestic and foreign literature were selected.Data extraction Data were mainly extracted from 61 articles which are listed in the reference section of this review.Results Glucocorticoids are steroid hormones secreted by the adrenal cortex that play a pivotal role in the regulation of a variety of developmental,metabolic and immune functions.However,high dose of exogenous glucocorticoids usage is the most common non-traumatic cause of ON FH.Glucocorticoids can affect the metabolisms of osteoblasts,osteoclasts,bone marrow stromal cells and adipocytes which decrease osteoblasts formation but increase adipocytes formation and cause ONFH finally.Conclusions Glucocorticoids affect the differentiation of mesenchymal stem cells,through activating or inhibiting the related transcript regulators of osteogenesis and adipogenesis.At last,the size and volume of mesenchymal stem cells derived adipocytes will increase amazingly,but the osteoblasts will be decreased obviously.In the meantime,the activity of the osteoclasts will be activated.So,these mechanisms work together and lead to ONFH.展开更多
Objective： To investigate the effect of Huogu II Formula （活骨 II方 ） with medicinal guide Radix Achyranthis Bidentatae （Ach） on bone marrow stem cells （BMSCs） homing to necrosis area after osteonecrosis of the...Objective： To investigate the effect of Huogu II Formula （活骨 II方 ） with medicinal guide Radix Achyranthis Bidentatae （Ach） on bone marrow stem cells （BMSCs） homing to necrosis area after osteonecrosis of the femoral head （ONFH） frozen by liquid nitrogen in rabbit as well as to explore the mechanism of prevention and treatment for ONFH. Methods： The animal model of ONFH was established by liquid nitrogen frozen on the rabbit left hind leg. Forty-eight Japanese White rabbits were randomly assigned to sham-operated group, model group, Huogu II group, and Huogu II plus Ach group, with 12 rabbits in each. During the course of ONFH animal model establishment, all rabbits were subcutaneously injected with recombinant human granulocyte colony-stimulating factor [rhG-CSF, 30 μg/（kg.day） for continuous 7 days]. Meanwhile, normal saline and decoction of the two formulae were administrated by gavage, respectively. White blood cells （WBC） were counted in peripheral blood before and after injection of rhG-CSF. Materials were drawn on the 2rid and 4th weeks after model built; bone glutamine protein （BGP） and bone morphogenetic protein 2 （BMP2） levels in serum were tested. Histopathologic changes were observed by hematoxylin and eosin （HE） staining. BMP2 mRNA levels were detected with in situ hybridization （iSH） staining. 5-Bromo-2＇-deoxyuridine （BrdU） and stromal cell derived factor 1 （SDF-1） were measured by immunohistochemical assay in femoral head of the left hind leg. Results： Compared with the shamoperated group, the ratio of empty lacuna, serum BGP, and SDF-1 level in the model group increased significantly, and BMP2 in both serum and femoral head decreased significantly. However, in comparison with the model group, the empty lacuna ratio of Huogu II group and Huogu II plus Ach group decreased obviously in addition to the levels of serum BGP and BMP2, and the expressions of BMP2 mRNA, BrdU, and SDF-1 increased significantly. Above changes were particularly obvious in Huogu II plus Ach group. BGP and SDF-1 on the 2nd week and empty lacuna rate and serum BMP2 level on the 4th week in Huogu II group significantly exceeded their counterparts. On the 2nd week, only in Huogu II plus Ach group that the BrdU counting rose significantly. On the 4th week, empty lacuna rate and serum BMP2 level in Huogu II plus Ach group exceeded those in Huogu II group distinctively. Conclusions： To a certain extent, the medicinal guide Ach improves the preventive and therapeutic effects of Huogu II Formula on expedmental ONFH model. The possible mechanism of this is related to its promoting effect on directional homing of BMSCs to the necrosis area.展开更多
Background:Accumulating evidence suggests that lithium influences mesenchymal stem cell(MSC)proliferation and osteogenic differentiation.As decreased bone formation in femoral heads is induced by glucocorticoids(GCs),...Background:Accumulating evidence suggests that lithium influences mesenchymal stem cell(MSC)proliferation and osteogenic differentiation.As decreased bone formation in femoral heads is induced by glucocorticoids(GCs),we hypothesized that lithium has a protective effect on GC-induced osteonecrosis of femoral heads(ONFH).Methods:A rat ONFH model was induced by methylprednisolone(MP)and the effect of lithium chloride on the models was evaluated.Micro-computed tomography(CT)-based angiography and bone scanning were performed to analyze the vessels and bone structure in the femoral heads.Hematoxylin and eosin and immunohistochemical staining were performed to evaluate the trabecular structure and osteocalcin(OCN)expression,respectively.Bone marrow-derived MSCs were isolated from the models,and their proliferative and osteogenic ability was evaluated.Western blotting and quantitative real-time polymerase chain reaction were performed to detect osteogenic-related proteins including Runx2,alkaline phosphatase,and Collagen I.Results:Micro-CT analysis showed a high degree of osteonecrotic changes in the rats that received only MP injection.Treatment with lithium reduced this significantly in rats that received lithium(MP+Li group);while 18/20 of the femoral heads in the MP showed severe osteonecrosis,only 5/20 in the MP+Li showed mild osteonecrotic changes.The MP+Li group also displayed a higher vessel volume than the MP group(0.2193 mm3vs.0.0811 mm3,P<0.05),shown by micro-CT-based angiography.Furthermore,histological analysis showed better trabecular structures and more OCN expression in the femoral heads of the MP+Li group compared with the MP group.The ex vivo investigation indicated higher proliferative and osteogenic ability and upregulated osteogenic-related proteins in MSCs extracted from rats in the MP+Li group than that in the MP group.Conclusions:We concluded that lithium chloride has a significant protective effect on GC-induced ONFH in rats and that lithium also enhances MSC proliferation and osteogenic differentiation in rats after GC administration.展开更多
Introduction: Osteonecrosis is the cellular death of the various components of bone. It mostly affects the femoral head, and its real incidence is unknown. Many causative factors may be involved in its genesis. In Sub...Introduction: Osteonecrosis is the cellular death of the various components of bone. It mostly affects the femoral head, and its real incidence is unknown. Many causative factors may be involved in its genesis. In Sub-Saharan Africa, it affects mainly young patients and the S and C hemoglobinopathies are the most affected backgrounds. Objective: To determine factors associated with aseptic osteonecrosis of the femoral head in hospital settings in Yaounde, Cameroon. Methodology: It was a cross-sectional multicentric study on 29,474 files of black Cameroonian patients seen during consultation or admission, within a five-year period, carried at the Central Hospital, the National Center for Rehabilitation of Handicaped Persons and at the FROT Clinic in Yaounde, Cameroon. Files of patients with aseptic osteonecrosis of the femoral head (1 file = 1 patient) were enrolled. The diagnosis was retained solely based on clinical and radiologic criteria. Magnetic resonance imaging, tomodencitometry and/or bone scintigraphy were also considered when available. Classification of lesions obeyed Ficat-Arlet criteria. Patients’ files with little information and hip diseases other than aseptic osteonecrosis were excluded. Results: Fifty-one cases (0.17%) of aseptic osteonecrosis were recruited;among them, there are 28 males (55%) and 23 females (45%). Their mean age was 38.9 ± 16.4 years (extremes: 7 and 78 years). Those aged 21 to 30 years represented 25.5% of cases. Pain and loss of function were present in all patients. The lesion occurred in the right hip in 22 cases (41.1%), and left hip in 13 cases (25.5%);16 patients (31.4%) had both hip affected. X-ray was performed for all patients. Radiologic lesions were at Stage IV in 2 cases (3.9%), III for 44 cases (86.3%), and II in 5 cases (9.8%). Factors associated with aseptic osteonecrosis were observed in 29 patients and their frequencies were as follows: sickle cell disease: n = 12 (25.3%);trauma: n = 10 (19.6%);alcoholism: n = 3 (5.9%);athletic practice: n = 3 (5.9%);and 2 patients (3.9%) were on treatment with steroid. HIV infection occurred in 2 cases (1.9%);dyslipidemia, hyperuricemia and systemic lupus erythematosus were diagnosed in 1 case (1.9%) each. Conclusion: The relative incidence of aseptic osteonecrosis of the femoral head in hospital settings in Yaounde is 0.17% and mostly young adults are affected. Lesions are discovered at an advanced radiographic stage and sickle cell disease is the first associated factor.展开更多
非创伤性股骨头坏死(nontraumatic osteonecrosis of the femoral head, NONFH)作为一种骨结构和生物力学的发生改变可导致髋关节功能丧失的一种难治性骨关节病,主要可分为糖皮质激素性和酒精性两大类。骨髓间充质干细胞(bone marrow me...非创伤性股骨头坏死(nontraumatic osteonecrosis of the femoral head, NONFH)作为一种骨结构和生物力学的发生改变可导致髋关节功能丧失的一种难治性骨关节病,主要可分为糖皮质激素性和酒精性两大类。骨髓间充质干细胞(bone marrow mesenchymal stem cells, BMSCs)作为保持骨稳态的主要干细胞,具有分化为成骨细胞、软骨细胞的能力。通过调控BMSCs向成骨细胞、软骨细胞分化对NONFH的修复和重建意义重大。中药在中医学“整体观念、辨证论治”理论指导下防治“骨蚀、骨痹”历史悠久、疗效显著。中药通过促进BMSCs向成骨细胞、软骨细胞分化,避免其向脂肪细胞分化,对NONFH的治疗有着重要意义。基于此,该文将中药调控BMSCs分化功能治疗NONFH最新研究进展进行综述,旨为NONFH相关研究的深入及临床防治提供思路和参考。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.
文摘It is estimated that 20000 to 30000 new patients are diagnosed with osteonecrosis annually accounting for approximately 10% of the 250000 total hip arthroplasties done annually in the United States. Thelack of level 1 evidence in the literature makes it difficult to identify optimal treatment protocols to manage patients with pre-collapse avascular necrosis of the femoral head, and early intervention prior to collapse is critical to successful outcomes in joint preserving procedures. There have been a variety of traumatic and atraumatic factors that have been identified as risk factors for osteonecrosis, but the etiology and pathogenesis still remains unclear. Current osteonecrosis diagnosis is dependent upon plain anteroposterior and frog-leg lateral radiographs of the hip, followed by magnetic resonance imaging(MRI). Generally, the first radiographic changes seen by radiograph will be cystic and sclerotic changes in the femoral head. Although the diagnosis may be made by radiograph, plain radiographs are generally insufficient for early diagnosis, therefore MRI is considered the most accurate benchmark. Treatment options include pharmacologic agents such as bisphosphonates and statins, biophysical treatments, as well as joint-preserving and joint-replacing surgeries. the surgical treatment of osteonecrosis of the femoral head can be divided into two major branches: femoral head sparing procedures(FHSP) and femoral head replacement procedures(FHRP). In general, FHSP are indicated at pre-collapse stages with minimal symptoms whereas FHRP are preferred at post-collapse symptomatic stages. It is difficult to know whether any treatment modality changes the natural history of core decompression since the true natural history of core decompression has not been delineated.
文摘Objective To review the recent developments in the mechanisms of glucocorticoids induced osteonecrosis of femoral head （ONFH） and introduce a new theory of ONFH.Data sources Both Chinese- and English-language literatures were searched using MEDLINE （1997-2011）,Pubmed （1997-2011 ） and the Index of Chinese-language Literature （1997-2011 ）.Study selection Data from published articles about mechanisms of glucocorticoids induced ONFH in recent domestic and foreign literature were selected.Data extraction Data were mainly extracted from 61 articles which are listed in the reference section of this review.Results Glucocorticoids are steroid hormones secreted by the adrenal cortex that play a pivotal role in the regulation of a variety of developmental,metabolic and immune functions.However,high dose of exogenous glucocorticoids usage is the most common non-traumatic cause of ON FH.Glucocorticoids can affect the metabolisms of osteoblasts,osteoclasts,bone marrow stromal cells and adipocytes which decrease osteoblasts formation but increase adipocytes formation and cause ONFH finally.Conclusions Glucocorticoids affect the differentiation of mesenchymal stem cells,through activating or inhibiting the related transcript regulators of osteogenesis and adipogenesis.At last,the size and volume of mesenchymal stem cells derived adipocytes will increase amazingly,but the osteoblasts will be decreased obviously.In the meantime,the activity of the osteoclasts will be activated.So,these mechanisms work together and lead to ONFH.
基金Supported by the National Natural Science Foundation of China (No.30672770)
文摘Objective： To investigate the effect of Huogu II Formula （活骨 II方 ） with medicinal guide Radix Achyranthis Bidentatae （Ach） on bone marrow stem cells （BMSCs） homing to necrosis area after osteonecrosis of the femoral head （ONFH） frozen by liquid nitrogen in rabbit as well as to explore the mechanism of prevention and treatment for ONFH. Methods： The animal model of ONFH was established by liquid nitrogen frozen on the rabbit left hind leg. Forty-eight Japanese White rabbits were randomly assigned to sham-operated group, model group, Huogu II group, and Huogu II plus Ach group, with 12 rabbits in each. During the course of ONFH animal model establishment, all rabbits were subcutaneously injected with recombinant human granulocyte colony-stimulating factor [rhG-CSF, 30 μg/（kg.day） for continuous 7 days]. Meanwhile, normal saline and decoction of the two formulae were administrated by gavage, respectively. White blood cells （WBC） were counted in peripheral blood before and after injection of rhG-CSF. Materials were drawn on the 2rid and 4th weeks after model built; bone glutamine protein （BGP） and bone morphogenetic protein 2 （BMP2） levels in serum were tested. Histopathologic changes were observed by hematoxylin and eosin （HE） staining. BMP2 mRNA levels were detected with in situ hybridization （iSH） staining. 5-Bromo-2＇-deoxyuridine （BrdU） and stromal cell derived factor 1 （SDF-1） were measured by immunohistochemical assay in femoral head of the left hind leg. Results： Compared with the shamoperated group, the ratio of empty lacuna, serum BGP, and SDF-1 level in the model group increased significantly, and BMP2 in both serum and femoral head decreased significantly. However, in comparison with the model group, the empty lacuna ratio of Huogu II group and Huogu II plus Ach group decreased obviously in addition to the levels of serum BGP and BMP2, and the expressions of BMP2 mRNA, BrdU, and SDF-1 increased significantly. Above changes were particularly obvious in Huogu II plus Ach group. BGP and SDF-1 on the 2nd week and empty lacuna rate and serum BMP2 level on the 4th week in Huogu II group significantly exceeded their counterparts. On the 2nd week, only in Huogu II plus Ach group that the BrdU counting rose significantly. On the 4th week, empty lacuna rate and serum BMP2 level in Huogu II plus Ach group exceeded those in Huogu II group distinctively. Conclusions： To a certain extent, the medicinal guide Ach improves the preventive and therapeutic effects of Huogu II Formula on expedmental ONFH model. The possible mechanism of this is related to its promoting effect on directional homing of BMSCs to the necrosis area.
基金supported by a grant from the National Natural Science Foundation of China(No.81702134).
文摘Background:Accumulating evidence suggests that lithium influences mesenchymal stem cell(MSC)proliferation and osteogenic differentiation.As decreased bone formation in femoral heads is induced by glucocorticoids(GCs),we hypothesized that lithium has a protective effect on GC-induced osteonecrosis of femoral heads(ONFH).Methods:A rat ONFH model was induced by methylprednisolone(MP)and the effect of lithium chloride on the models was evaluated.Micro-computed tomography(CT)-based angiography and bone scanning were performed to analyze the vessels and bone structure in the femoral heads.Hematoxylin and eosin and immunohistochemical staining were performed to evaluate the trabecular structure and osteocalcin(OCN)expression,respectively.Bone marrow-derived MSCs were isolated from the models,and their proliferative and osteogenic ability was evaluated.Western blotting and quantitative real-time polymerase chain reaction were performed to detect osteogenic-related proteins including Runx2,alkaline phosphatase,and Collagen I.Results:Micro-CT analysis showed a high degree of osteonecrotic changes in the rats that received only MP injection.Treatment with lithium reduced this significantly in rats that received lithium(MP+Li group);while 18/20 of the femoral heads in the MP showed severe osteonecrosis,only 5/20 in the MP+Li showed mild osteonecrotic changes.The MP+Li group also displayed a higher vessel volume than the MP group(0.2193 mm3vs.0.0811 mm3,P<0.05),shown by micro-CT-based angiography.Furthermore,histological analysis showed better trabecular structures and more OCN expression in the femoral heads of the MP+Li group compared with the MP group.The ex vivo investigation indicated higher proliferative and osteogenic ability and upregulated osteogenic-related proteins in MSCs extracted from rats in the MP+Li group than that in the MP group.Conclusions:We concluded that lithium chloride has a significant protective effect on GC-induced ONFH in rats and that lithium also enhances MSC proliferation and osteogenic differentiation in rats after GC administration.
文摘Introduction: Osteonecrosis is the cellular death of the various components of bone. It mostly affects the femoral head, and its real incidence is unknown. Many causative factors may be involved in its genesis. In Sub-Saharan Africa, it affects mainly young patients and the S and C hemoglobinopathies are the most affected backgrounds. Objective: To determine factors associated with aseptic osteonecrosis of the femoral head in hospital settings in Yaounde, Cameroon. Methodology: It was a cross-sectional multicentric study on 29,474 files of black Cameroonian patients seen during consultation or admission, within a five-year period, carried at the Central Hospital, the National Center for Rehabilitation of Handicaped Persons and at the FROT Clinic in Yaounde, Cameroon. Files of patients with aseptic osteonecrosis of the femoral head (1 file = 1 patient) were enrolled. The diagnosis was retained solely based on clinical and radiologic criteria. Magnetic resonance imaging, tomodencitometry and/or bone scintigraphy were also considered when available. Classification of lesions obeyed Ficat-Arlet criteria. Patients’ files with little information and hip diseases other than aseptic osteonecrosis were excluded. Results: Fifty-one cases (0.17%) of aseptic osteonecrosis were recruited;among them, there are 28 males (55%) and 23 females (45%). Their mean age was 38.9 ± 16.4 years (extremes: 7 and 78 years). Those aged 21 to 30 years represented 25.5% of cases. Pain and loss of function were present in all patients. The lesion occurred in the right hip in 22 cases (41.1%), and left hip in 13 cases (25.5%);16 patients (31.4%) had both hip affected. X-ray was performed for all patients. Radiologic lesions were at Stage IV in 2 cases (3.9%), III for 44 cases (86.3%), and II in 5 cases (9.8%). Factors associated with aseptic osteonecrosis were observed in 29 patients and their frequencies were as follows: sickle cell disease: n = 12 (25.3%);trauma: n = 10 (19.6%);alcoholism: n = 3 (5.9%);athletic practice: n = 3 (5.9%);and 2 patients (3.9%) were on treatment with steroid. HIV infection occurred in 2 cases (1.9%);dyslipidemia, hyperuricemia and systemic lupus erythematosus were diagnosed in 1 case (1.9%) each. Conclusion: The relative incidence of aseptic osteonecrosis of the femoral head in hospital settings in Yaounde is 0.17% and mostly young adults are affected. Lesions are discovered at an advanced radiographic stage and sickle cell disease is the first associated factor.
