In recent years,growth hormone and insulin-like growth factors have become key regulators of bone metabolism and remodeling,crucial for maintaining healthy bone mass throughout life.Studies have shown that adult growt...In recent years,growth hormone and insulin-like growth factors have become key regulators of bone metabolism and remodeling,crucial for maintaining healthy bone mass throughout life.Studies have shown that adult growth hormone deficiency leads to alterations in bone remodeling,significantly affecting bone microarchitecture and increasing fracture risk.Although recombinant human growth hormone replacement therapy can mitigate these adverse effects,improving bone density,and reduce fracture risk,its effectiveness in treating osteoporosis,especially in adults with established growth hormone deficiency,seems limited.Bisphosphonates inhibit bone resorption by targeting farnesyl pyrophosphate synthase in osteoclasts,and clinical trials have confirmed their efficacy in improving osteoporosis.Therefore,for adult growth hormone deficiency patients with osteoporosis,the use of bisphosphonates alongside growth hormone replacement therapy is recommended.展开更多
The treatment and signaling pathway regulation effects of kidney-tonifying traditional Chinese medicine on osteoporosis have been widely studied,but without a systematic summary currently.This review comprehensively c...The treatment and signaling pathway regulation effects of kidney-tonifying traditional Chinese medicine on osteoporosis have been widely studied,but without a systematic summary currently.This review comprehensively collected and analyzed the traditional Chinese medicine on the treatment and signaling pathway regulation of osteoporosis in recent ten years,such as Epimedium,Drynariae Rhizoma,Cnidium,Eucommia,Psoralen and Dipsacus.Based on the existing findings,we concluded the following conclusions:(1)kidney-tonifying traditional Chinese medicine treats osteoporosis mainly through BMP-Smads,Wnt/β-catenin,MAPK,PI3K/AKT signaling pathway to promote osteoblast bone formation and through OPG/RANKL/RANK,estrogen,CTSK signaling pathway to inhibit osteoclasts of bone resorption.(1)Epimedium,Drynariae Rhizoma,Cnidium and Psoralen up-regulate the key proteins and genes of BMP-Smads and Wnt/β-catenin signaling pathways to promote bone formation.(2)Epimedium,Drynariae Rhizoma,Cnidium,Eucommia,Psoralen,Dipsacusinhibit the bone resorption by mediating the OPG/RANKL/RANK signaling pathway.(2)Kidney-tonifying traditional Chinese medicine prevent and treat osteoporosis through a variety of ways:Icariin,Naringin,Osthol,Psoralen can regulate BMP-Smads,Wnt/β-catenin signaling pathway to promote bone formation,but also activate OPG/RANKL/RANK,CTSK and other signaling pathway to inhibit bone resorption.(3)The crosstalk of the signaling pathways and the animal experiments of the traditional Chinese medicine on the prevention and treatment of osteoporosis as well as their multi-target mechanism and comprehensive regulation need further clarification.展开更多
OBJECTIVE To evaluate antioxidant,anti-inflammatory,antimicrobial activities of Pinus Roxburghii stem bark in vitro and evaluation of in vivo anti-osteoporotic activity in female rats.METHODS The antioxidant activity ...OBJECTIVE To evaluate antioxidant,anti-inflammatory,antimicrobial activities of Pinus Roxburghii stem bark in vitro and evaluation of in vivo anti-osteoporotic activity in female rats.METHODS The antioxidant activity of plant extract was assessed using DPPH,nitric oxide and H2O2 radical scavenging methods.In vitro anti-inflammatory activity was evaluated using albumin denaturation,membrane stabilization methods at various concentrations.The antibacterial and anti-fungal activity of extracts was also done against micro-organisms:Pseudomonas aurignosa,Escherichia coli,Staphylococcus aureus,Bacillus subtilis and Candida albicans.Quantitative analysis of total phenolics,flavonoids and tannins were also estimated.Female Wistar albino rats(220-260g)were employed and ovaries were surgically removed bilaterally in anaesthesia which causes post-menopausal syndrome in all the groups except sham operated rats.Extracts of Pinus roxburghii stem at 100 and 200mg·kg-1,po.and tamoxifen as standard 1mg·kg-1,po.were given.Acute toxicity study was also done.RESULTS Treatment with Pinus roxburghii extract in two doses significantly(P<0.05)ameliorated surgical ovariectomy induced biochemical and biomechanical changes like decrease in bone density,bone strength,alkaline phosphatase,serum calcium,serum phosphorous and increase in urine hydroxylproline levels.Plant extract also has significant(P<0.05)antioxidant,antimicrobial and anti-inflammatory activities.CONCLUSION The assessments done in present investigation may conclude that the constituents of Pinus roxburghii has significant potential in ameliorating oxidative,inflammatory reactions and possesses anti-microbial;osteobalstic and osteoclastic activities used for calcium homeostatis and improved bone strength in female rats.展开更多
Objective To observe the value of artificial intelligence(AI)models based on non-contrast chest CT for measuring bone mineral density(BMD).Methods Totally 380 subjects who underwent both non-contrast chest CT and quan...Objective To observe the value of artificial intelligence(AI)models based on non-contrast chest CT for measuring bone mineral density(BMD).Methods Totally 380 subjects who underwent both non-contrast chest CT and quantitative CT(QCT)BMD examination were retrospectively enrolled and divided into training set(n=304)and test set(n=76)at a ratio of 8∶2.The mean BMD of L1—L3 vertebrae were measured based on QCT.Spongy bones of T5—T10 vertebrae were segmented as ROI,radiomics(Rad)features were extracted,and machine learning(ML),Rad and deep learning(DL)models were constructed for classification of osteoporosis(OP)and evaluating BMD,respectively.Receiver operating characteristic curves were drawn,and area under the curves(AUC)were calculated to evaluate the efficacy of each model for classification of OP.Bland-Altman analysis and Pearson correlation analysis were performed to explore the consistency and correlation of each model with QCT for measuring BMD.Results Among ML and Rad models,ML Bagging-OP and Rad Bagging-OP had the best performances for classification of OP.In test set,AUC of ML Bagging-OP,Rad Bagging-OP and DL OP for classification of OP was 0.943,0.944 and 0.947,respectively,with no significant difference(all P>0.05).BMD obtained with all the above models had good consistency with those measured with QCT(most of the differences were within the range of Ax-G±1.96 s),which were highly positively correlated(r=0.910—0.974,all P<0.001).Conclusion AI models based on non-contrast chest CT had high efficacy for classification of OP,and good consistency of BMD measurements were found between AI models and QCT.展开更多
Introduction Aging shifts bone remodeling toward a negative balance between bone formation and resorption,causing bone loss and increased fracture risk.Anti-resorptive agents are commonly used to inhibit bone resorpti...Introduction Aging shifts bone remodeling toward a negative balance between bone formation and resorption,causing bone loss and increased fracture risk.Anti-resorptive agents are commonly used to inhibit bone resorption and stabilize bone mass.While they are effective to prevent further bone loss,there is also a great need for anabolic agents which can reverse bone deterioration and regain lost skeletal integrity.PTH,the only FDA-approved anabolic treatment for osteoporosis,greatly stimulates bone formation.Combined therapy of anti-resorptive treatments,such as alendronate(ALN),and PTH have been proposed and are expected to further increase bone mass.However,studies show conflicting results regarding the effectiveness展开更多
Our previous investigation found that exendin-4 （Ex-4） , a peptide analogue of glucagon-like peptide 1 （GLP-1） , induced bone formation probably by osteoblast activation. Nevertheless, previous investigations did ...Our previous investigation found that exendin-4 （Ex-4） , a peptide analogue of glucagon-like peptide 1 （GLP-1） , induced bone formation probably by osteoblast activation. Nevertheless, previous investigations did not observe any expression of GLP-1 receptors in osteoblasts, indicating that the direct cell target of GLP-1 and its ana- logues might not be osteoblasts but some other types of cells yet to be identified. To elucidate the underlying mecha- nisms, we performed further investigation in the present study and found that GLP-1 receptor was only identified in bone marrow mesenchymal stem cells （BMSCs）. Furthermore, activation of GLP-1 receptor by Ex-4 promoted the differentiation of B MSCs into osteoblast, which was associated with activation of PKA, nuclear translocation of [5- catenin, activation of PI3K/AKT and inhibition of GSK3β. Ex-4 also inhibited the adipocyte differentiation of BM- SCs, as evidenced by inhibition of PPARγ, lipoprotein lipase expression and lipid production. Blockade of GLP-1 receptor, PKA, PI3K or Wnt pathway, or respective knock-down of GLP-1 receptor and β-catenin in BMSCs inhib- ited the Ex-4 mediated effects. The results indicated that the GLP-1 receptor mediated osteoblastic differentiation and bone formation through stimulation of PKA/β-catenin signaling and inhibition of PKA/PI3IC/AKT/GSK3β？ signaling pathway in BMSCs. The findings reveal a new role of GLP-1 receptor for regulating osteoblastic differentia- tion of B MSCs and may provide a molecular basis for novel anabolic therapeutics against osteoporosis.展开更多
基金This work was supported by the Special Project of Performance Incentive and Guidance for Scientific Research Institutions of Chongqing,China (jxyn2022-5)。
文摘In recent years,growth hormone and insulin-like growth factors have become key regulators of bone metabolism and remodeling,crucial for maintaining healthy bone mass throughout life.Studies have shown that adult growth hormone deficiency leads to alterations in bone remodeling,significantly affecting bone microarchitecture and increasing fracture risk.Although recombinant human growth hormone replacement therapy can mitigate these adverse effects,improving bone density,and reduce fracture risk,its effectiveness in treating osteoporosis,especially in adults with established growth hormone deficiency,seems limited.Bisphosphonates inhibit bone resorption by targeting farnesyl pyrophosphate synthase in osteoclasts,and clinical trials have confirmed their efficacy in improving osteoporosis.Therefore,for adult growth hormone deficiency patients with osteoporosis,the use of bisphosphonates alongside growth hormone replacement therapy is recommended.
文摘The treatment and signaling pathway regulation effects of kidney-tonifying traditional Chinese medicine on osteoporosis have been widely studied,but without a systematic summary currently.This review comprehensively collected and analyzed the traditional Chinese medicine on the treatment and signaling pathway regulation of osteoporosis in recent ten years,such as Epimedium,Drynariae Rhizoma,Cnidium,Eucommia,Psoralen and Dipsacus.Based on the existing findings,we concluded the following conclusions:(1)kidney-tonifying traditional Chinese medicine treats osteoporosis mainly through BMP-Smads,Wnt/β-catenin,MAPK,PI3K/AKT signaling pathway to promote osteoblast bone formation and through OPG/RANKL/RANK,estrogen,CTSK signaling pathway to inhibit osteoclasts of bone resorption.(1)Epimedium,Drynariae Rhizoma,Cnidium and Psoralen up-regulate the key proteins and genes of BMP-Smads and Wnt/β-catenin signaling pathways to promote bone formation.(2)Epimedium,Drynariae Rhizoma,Cnidium,Eucommia,Psoralen,Dipsacusinhibit the bone resorption by mediating the OPG/RANKL/RANK signaling pathway.(2)Kidney-tonifying traditional Chinese medicine prevent and treat osteoporosis through a variety of ways:Icariin,Naringin,Osthol,Psoralen can regulate BMP-Smads,Wnt/β-catenin signaling pathway to promote bone formation,but also activate OPG/RANKL/RANK,CTSK and other signaling pathway to inhibit bone resorption.(3)The crosstalk of the signaling pathways and the animal experiments of the traditional Chinese medicine on the prevention and treatment of osteoporosis as well as their multi-target mechanism and comprehensive regulation need further clarification.
基金The project supported by Department of Science and Technology(DST),New Delhi
文摘OBJECTIVE To evaluate antioxidant,anti-inflammatory,antimicrobial activities of Pinus Roxburghii stem bark in vitro and evaluation of in vivo anti-osteoporotic activity in female rats.METHODS The antioxidant activity of plant extract was assessed using DPPH,nitric oxide and H2O2 radical scavenging methods.In vitro anti-inflammatory activity was evaluated using albumin denaturation,membrane stabilization methods at various concentrations.The antibacterial and anti-fungal activity of extracts was also done against micro-organisms:Pseudomonas aurignosa,Escherichia coli,Staphylococcus aureus,Bacillus subtilis and Candida albicans.Quantitative analysis of total phenolics,flavonoids and tannins were also estimated.Female Wistar albino rats(220-260g)were employed and ovaries were surgically removed bilaterally in anaesthesia which causes post-menopausal syndrome in all the groups except sham operated rats.Extracts of Pinus roxburghii stem at 100 and 200mg·kg-1,po.and tamoxifen as standard 1mg·kg-1,po.were given.Acute toxicity study was also done.RESULTS Treatment with Pinus roxburghii extract in two doses significantly(P<0.05)ameliorated surgical ovariectomy induced biochemical and biomechanical changes like decrease in bone density,bone strength,alkaline phosphatase,serum calcium,serum phosphorous and increase in urine hydroxylproline levels.Plant extract also has significant(P<0.05)antioxidant,antimicrobial and anti-inflammatory activities.CONCLUSION The assessments done in present investigation may conclude that the constituents of Pinus roxburghii has significant potential in ameliorating oxidative,inflammatory reactions and possesses anti-microbial;osteobalstic and osteoclastic activities used for calcium homeostatis and improved bone strength in female rats.
文摘Objective To observe the value of artificial intelligence(AI)models based on non-contrast chest CT for measuring bone mineral density(BMD).Methods Totally 380 subjects who underwent both non-contrast chest CT and quantitative CT(QCT)BMD examination were retrospectively enrolled and divided into training set(n=304)and test set(n=76)at a ratio of 8∶2.The mean BMD of L1—L3 vertebrae were measured based on QCT.Spongy bones of T5—T10 vertebrae were segmented as ROI,radiomics(Rad)features were extracted,and machine learning(ML),Rad and deep learning(DL)models were constructed for classification of osteoporosis(OP)and evaluating BMD,respectively.Receiver operating characteristic curves were drawn,and area under the curves(AUC)were calculated to evaluate the efficacy of each model for classification of OP.Bland-Altman analysis and Pearson correlation analysis were performed to explore the consistency and correlation of each model with QCT for measuring BMD.Results Among ML and Rad models,ML Bagging-OP and Rad Bagging-OP had the best performances for classification of OP.In test set,AUC of ML Bagging-OP,Rad Bagging-OP and DL OP for classification of OP was 0.943,0.944 and 0.947,respectively,with no significant difference(all P>0.05).BMD obtained with all the above models had good consistency with those measured with QCT(most of the differences were within the range of Ax-G±1.96 s),which were highly positively correlated(r=0.910—0.974,all P<0.001).Conclusion AI models based on non-contrast chest CT had high efficacy for classification of OP,and good consistency of BMD measurements were found between AI models and QCT.
基金supported by McCabe pilot award and the Penn Center for Musculoskeletal Disorders(NIH/NIAMS P30AR050950)
文摘Introduction Aging shifts bone remodeling toward a negative balance between bone formation and resorption,causing bone loss and increased fracture risk.Anti-resorptive agents are commonly used to inhibit bone resorption and stabilize bone mass.While they are effective to prevent further bone loss,there is also a great need for anabolic agents which can reverse bone deterioration and regain lost skeletal integrity.PTH,the only FDA-approved anabolic treatment for osteoporosis,greatly stimulates bone formation.Combined therapy of anti-resorptive treatments,such as alendronate(ALN),and PTH have been proposed and are expected to further increase bone mass.However,studies show conflicting results regarding the effectiveness
文摘Our previous investigation found that exendin-4 （Ex-4） , a peptide analogue of glucagon-like peptide 1 （GLP-1） , induced bone formation probably by osteoblast activation. Nevertheless, previous investigations did not observe any expression of GLP-1 receptors in osteoblasts, indicating that the direct cell target of GLP-1 and its ana- logues might not be osteoblasts but some other types of cells yet to be identified. To elucidate the underlying mecha- nisms, we performed further investigation in the present study and found that GLP-1 receptor was only identified in bone marrow mesenchymal stem cells （BMSCs）. Furthermore, activation of GLP-1 receptor by Ex-4 promoted the differentiation of B MSCs into osteoblast, which was associated with activation of PKA, nuclear translocation of [5- catenin, activation of PI3K/AKT and inhibition of GSK3β. Ex-4 also inhibited the adipocyte differentiation of BM- SCs, as evidenced by inhibition of PPARγ, lipoprotein lipase expression and lipid production. Blockade of GLP-1 receptor, PKA, PI3K or Wnt pathway, or respective knock-down of GLP-1 receptor and β-catenin in BMSCs inhib- ited the Ex-4 mediated effects. The results indicated that the GLP-1 receptor mediated osteoblastic differentiation and bone formation through stimulation of PKA/β-catenin signaling and inhibition of PKA/PI3IC/AKT/GSK3β？ signaling pathway in BMSCs. The findings reveal a new role of GLP-1 receptor for regulating osteoblastic differentia- tion of B MSCs and may provide a molecular basis for novel anabolic therapeutics against osteoporosis.
