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
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
The decreased osteoblast differentiation associated with reduced bone formation is one main cause of microgravityinduced bone loss.Our previous studies have demonstrated that microtubule actin crosslinking factor 1(MA...The decreased osteoblast differentiation associated with reduced bone formation is one main cause of microgravityinduced bone loss.Our previous studies have demonstrated that microtubule actin crosslinking factor 1(MACF1)is downregulated in association with the decreased osteoblast differentiation and bone formation under simulated microgravity conditions.These findings suggest that MACF1 is sensitive to mechanical condition and may be critical for osteoblast differentiation and bone formation.To verify this hypothesis,current study investigates the role and mechanism of MACF1 in regulatingosteoblast differentiation by adopting MACF1 knockdown(MACF1-KD)osteoblasts.The results showed that MACF1 knockdown suppressed mineralized nodules formation,alkaline phosphatase(ALP)activity,osteogenic gene expression andβ-catenin signaling transduction.Moreover,we used RNA sequencing(RNA-seq)and chromatin immunoprecipitation sequencing(ChIP-seq)to investigate further mechanism.Interestingly,we found that MACF1 sequesterd repressors of osteoblast differentiation in cytoplasm.In conclusion,MACF1 is sensitive to mechanical condition and plays key role in activatingβ-catenin signaling transduction and sequestering repressors of osteoblast differentiation,which further promotes osteoblast differentiation.展开更多
OBJECTIVE To investigated the role of SIRT6 in the survival of osteoblast cel s against hypoxia stimulus as wel as the underlying mechanism. METHODS MC3T3-E1 osteoblast cel s were used. Apoptosis was induced by hypoxi...OBJECTIVE To investigated the role of SIRT6 in the survival of osteoblast cel s against hypoxia stimulus as wel as the underlying mechanism. METHODS MC3T3-E1 osteoblast cel s were used. Apoptosis was induced by hypoxic treatment. MC3T3-E1 cells were transfected with adenovirus SIRT6. For SIRT6 silencing experiment,the transfection of cells were done using three si RNA duplexes directed at different regions of SIRT6 or scrambled siRNA pool. The relative levels of SIRT6 mR NA were quantifiedby using real-time PCR. Western blotting experiments were done after the specific treatment and sample collection. MTT assay was used to estimate cell viability. Caspase 3/7 activity was assayed. RESULTS The expression of SIRT6 mR NA appeared to be markedly down-regulated in the hypoxia-treated group compared to the matched normal group. Meanwhile,western blotting analysis revealed that the expression of SIRT6 level was markedly down-regulated in hypoxia-treated group at protein level. SIRT6 level was effectively down-regulated by the transfection of SIRT6 si RNA,and significantly enhanced by SIRT6 overexpression. Compared with the control group,SIRT6 overexpression could significantly increase cell viability,and significantly decrease the percentage of apoptotic cel s and the activity of caspase 3/7 in response to hypoxia treatment. By contrast,SIRT6 knockdown via treatment with SIRT6 si RNA exhibited the opposite phenotype. CONCLUSION These results suggest that SIRT6 plays a protective role in hypoxia-induced apoptosis in MC3T3-E1 cells,and that strategies might be beneficial for the treatment of ischemic bone disease.展开更多
OBJECTIVE To investigate the effect of Pinctadafucata mantle gene 1(pfmg1)on osteoporotic bone lossand the role in osteoblast differentiation and matrix mineralization,and to explore the molecular mechanismof how PFMG...OBJECTIVE To investigate the effect of Pinctadafucata mantle gene 1(pfmg1)on osteoporotic bone lossand the role in osteoblast differentiation and matrix mineralization,and to explore the molecular mechanismof how PFMG1 functions through both animal and cellular experiments.METHODS For animal experiments,female BALB/c mice were subjected to sham-operation(sham)or ovariectomy(ovx)at 5weeks of age,control and pfmg1 lentiviral particles were packaged and injected through tail vein to ovx mice(2×107TU/mouse),respectively.Bone mineral density(BMD)was detected 2 months after the surgery,and the proximal tibia was scanned in three dimensions byμCT.For cellular experiments,GST-PFMG1 protein was expressed and purified,then added to MC3T3E1 cell culture medium.MTT,ALP activity and the level of matrix mineralization were detected after the treatment.RESULTSEctopic expression of pfmg1 gene enhanced the BMD level of ovx mice.μCT images revealed that PFMG1 improvedthe osteoporotic characteristics caused by ovariectomy,including the decreases in trabecular number(Tb.N),trabecular thickness(Tb.Th),and in trabecular bone volume as a percentage of total bone volume(BV/TV);and the increases in trabecular spacing(Tb.Sp)and trabecular bone pattern factor(TBPf).The alkaline phosphatase(ALP)activity and the level of matrix mineralization increased,while the MTT activity decreased after treated with PFMG1 in the osteoblast cell line MC3T3E1.CONCLUSION PFMG1 from the mental of P.fucatacould promote osteoblast differentiation and matrix mineralization in vitro,and couldprevent bone loss caused by ovariectomy in vivo.These findings showed the potential of PFMG1 from nacre as a therapeutic drug for osteoporosis.展开更多
Introduction Mechanotransduction has demonstrated potentials for tissue adaptation in vivo and in vitro. It is well documented that ultrasound,as a mechanical signal,can produce a wide variety of biological effects in...Introduction Mechanotransduction has demonstrated potentials for tissue adaptation in vivo and in vitro. It is well documented that ultrasound,as a mechanical signal,can produce a wide variety of biological effects in vitro and in vivo [1]. As an example,展开更多
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.
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.
基金supported by the National Natural Science Foundation of China ( 81772017,31570940)Young Talent Fund of University Association for Science and Technology in Shaanxi,China ( 20170401)Supported by Natural Science Basic Research Plan in Shaanxi Province of China ( 2018JM3040)
文摘The decreased osteoblast differentiation associated with reduced bone formation is one main cause of microgravityinduced bone loss.Our previous studies have demonstrated that microtubule actin crosslinking factor 1(MACF1)is downregulated in association with the decreased osteoblast differentiation and bone formation under simulated microgravity conditions.These findings suggest that MACF1 is sensitive to mechanical condition and may be critical for osteoblast differentiation and bone formation.To verify this hypothesis,current study investigates the role and mechanism of MACF1 in regulatingosteoblast differentiation by adopting MACF1 knockdown(MACF1-KD)osteoblasts.The results showed that MACF1 knockdown suppressed mineralized nodules formation,alkaline phosphatase(ALP)activity,osteogenic gene expression andβ-catenin signaling transduction.Moreover,we used RNA sequencing(RNA-seq)and chromatin immunoprecipitation sequencing(ChIP-seq)to investigate further mechanism.Interestingly,we found that MACF1 sequesterd repressors of osteoblast differentiation in cytoplasm.In conclusion,MACF1 is sensitive to mechanical condition and plays key role in activatingβ-catenin signaling transduction and sequestering repressors of osteoblast differentiation,which further promotes osteoblast differentiation.
基金The project supported by grants from Shandong Provincial Natural Science Foundation,China(ZR2014CQ037)National Training Programs of Innovation and Entrepreneurship for Undergraduates,China(201610439244)National Natural Science Foundation of China(81400182)
文摘OBJECTIVE To investigated the role of SIRT6 in the survival of osteoblast cel s against hypoxia stimulus as wel as the underlying mechanism. METHODS MC3T3-E1 osteoblast cel s were used. Apoptosis was induced by hypoxic treatment. MC3T3-E1 cells were transfected with adenovirus SIRT6. For SIRT6 silencing experiment,the transfection of cells were done using three si RNA duplexes directed at different regions of SIRT6 or scrambled siRNA pool. The relative levels of SIRT6 mR NA were quantifiedby using real-time PCR. Western blotting experiments were done after the specific treatment and sample collection. MTT assay was used to estimate cell viability. Caspase 3/7 activity was assayed. RESULTS The expression of SIRT6 mR NA appeared to be markedly down-regulated in the hypoxia-treated group compared to the matched normal group. Meanwhile,western blotting analysis revealed that the expression of SIRT6 level was markedly down-regulated in hypoxia-treated group at protein level. SIRT6 level was effectively down-regulated by the transfection of SIRT6 si RNA,and significantly enhanced by SIRT6 overexpression. Compared with the control group,SIRT6 overexpression could significantly increase cell viability,and significantly decrease the percentage of apoptotic cel s and the activity of caspase 3/7 in response to hypoxia treatment. By contrast,SIRT6 knockdown via treatment with SIRT6 si RNA exhibited the opposite phenotype. CONCLUSION These results suggest that SIRT6 plays a protective role in hypoxia-induced apoptosis in MC3T3-E1 cells,and that strategies might be beneficial for the treatment of ischemic bone disease.
基金The project supported by Tsinghua University Initiative Scientific Research Program(2011THZ0)the National Natural Science Foundation of China(81270425)
文摘OBJECTIVE To investigate the effect of Pinctadafucata mantle gene 1(pfmg1)on osteoporotic bone lossand the role in osteoblast differentiation and matrix mineralization,and to explore the molecular mechanismof how PFMG1 functions through both animal and cellular experiments.METHODS For animal experiments,female BALB/c mice were subjected to sham-operation(sham)or ovariectomy(ovx)at 5weeks of age,control and pfmg1 lentiviral particles were packaged and injected through tail vein to ovx mice(2×107TU/mouse),respectively.Bone mineral density(BMD)was detected 2 months after the surgery,and the proximal tibia was scanned in three dimensions byμCT.For cellular experiments,GST-PFMG1 protein was expressed and purified,then added to MC3T3E1 cell culture medium.MTT,ALP activity and the level of matrix mineralization were detected after the treatment.RESULTSEctopic expression of pfmg1 gene enhanced the BMD level of ovx mice.μCT images revealed that PFMG1 improvedthe osteoporotic characteristics caused by ovariectomy,including the decreases in trabecular number(Tb.N),trabecular thickness(Tb.Th),and in trabecular bone volume as a percentage of total bone volume(BV/TV);and the increases in trabecular spacing(Tb.Sp)and trabecular bone pattern factor(TBPf).The alkaline phosphatase(ALP)activity and the level of matrix mineralization increased,while the MTT activity decreased after treated with PFMG1 in the osteoblast cell line MC3T3E1.CONCLUSION PFMG1 from the mental of P.fucatacould promote osteoblast differentiation and matrix mineralization in vitro,and couldprevent bone loss caused by ovariectomy in vivo.These findings showed the potential of PFMG1 from nacre as a therapeutic drug for osteoporosis.
基金supported by the NIH (R01 AR52379 & R01 AR49286),U S Army Medical Research and NSBRI
文摘Introduction Mechanotransduction has demonstrated potentials for tissue adaptation in vivo and in vitro. It is well documented that ultrasound,as a mechanical signal,can produce a wide variety of biological effects in vitro and in vivo [1]. As an example,
