Although bone morphogenetic proteins(BMPs)initially showed effective induction of ectopic bone growth in muscle,it has since been determined that these proteins,as members of the TGF-b superfamily,play a diverse and c...Although bone morphogenetic proteins(BMPs)initially showed effective induction of ectopic bone growth in muscle,it has since been determined that these proteins,as members of the TGF-b superfamily,play a diverse and critical array of biological roles.These roles include regulating skeletal and bone formation,angiogenesis,and development and homeostasis of multiple organ systems.Disruptions of the members of the TGF-b/BMP superfamily result in severe skeletal and extra-skeletal irregularities,suggesting high therapeutic potential from understanding this family of BMP proteins.Although it was once one of the least characterized BMPs,BMP9 has revealed itself to have the highest osteogenic potential across numerous experiments both in vitro and in vivo,with recent studies suggesting that the exceptional potency of BMP9 may result from unique signaling pathways that differentiate it from other BMPs.The effectiveness of BMP9 in inducing bone formation was recently revealed in promising experiments that demonstrated efficacy in the repair of critical sized cranial defects as well as compatibility with bone-inducing bio-implants,revealing the great translational promise of BMP9.Furthermore,emerging evidence indicates that,besides its osteogenic activity,BMP9 exerts a broad range of biological functions,including stem cell differentiation,angiogenesis,neurogenesis,tumorigenesis,and metabolism.This review aims to summarize our current understanding of BMP9 across biology and the body.展开更多
OBJECTIVE： To investigate the effects of Huogu I formula on regulation of lipid metabolism in ste- roid-induced osteonecrosis of the femoral head （SONFH） rats and verify our hypothesis that Huogu I formula regulat...OBJECTIVE： To investigate the effects of Huogu I formula on regulation of lipid metabolism in ste- roid-induced osteonecrosis of the femoral head （SONFH） rats and verify our hypothesis that Huogu I formula regulates lipid metabolism by down-regulating peroxisome proliferator-activated receptor gamma （PPARy） expression and activating Wnt signaling pathways. METHODS： Eighty-five rats were divided into four groups： control, model, Huogu 15 g/kg and Huogu 30 g/kg. Six weeks later, animals were anaesthe- tized, femora were dissected for histopathologicalexamination of the osteonecrotic changes and re- pair processes, micro computed tomography （Mi- cro-CT）-based micro-angiography was performed to assess vascularization. Serum lipid levels were detected by haematological examination. The ex- pressions of PPARy, Wnt3a, low density lipoprotein receptor-related protein 5 （LRP5） and 13-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 ~ formula treatment groups. By micro-CT quantification, Huogu ~ formula treat- ment 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 ex- pression of PPARy and increase the expressions of Wnt3a, LRP5 and 13-catenin at both protein and mRNA levels. CONCLUSION： The results of our present study highlight the lipid-lowering potential of Huogu Ⅰ formula, and provide further evidence of the in- volvement of the PPARy inhibition and Wnt/LRPS/ 13-catenin signaling activation in the effects of Huogu Ⅰ formula.展开更多
Adipose tissue is a major metabolic organ, and it has been traditionally classified as either white adipose tissue(WAT) or brown adipose tissue(BAT). WAT and BAT are characterized by different anatomical locations, mo...Adipose tissue is a major metabolic organ, and it has been traditionally classified as either white adipose tissue(WAT) or brown adipose tissue(BAT). WAT and BAT are characterized by different anatomical locations, morphological structures, functions, and regulations. WAT and BAT are both involved in energy balance. WAT is mainly involved in the storage and mobilization of energy in the form of triglycerides, whereas BAT specializes in dissipating energy as heat during cold- or diet-induced thermogenesis. Recently, brownlike adipocytes were discovered in WAT. These brownlike adipocytes that appear in WAT are called beige or brite adipocytes. Interestingly, these beige/brite cells resemble white fat cells in the basal state, but they respond to thermogenic stimuli with increased levels of thermogenic genes and increased respiration rates. In addition, beige/brite cells have a gene expressionpattern distinct from that of either white or brown fat cells. The current epidemic of obesity has increased the interest in studying adipocyte formation(adipogenesis), especially in beige/brite cells. This review summarizes the developmental process of adipose tissues that originate from the mesenchymal stem cells and the features of these three different types of adipocytes.展开更多
Objective： To observe the function of wnt/β-catenin signal pathway on the process that epimedium-derived flavonoids （EFs） regulate the balance between osteogenic differentiation and adipogenic differentiation in b...Objective： To observe the function of wnt/β-catenin signal pathway on the process that epimedium-derived flavonoids （EFs） regulate the balance between osteogenic differentiation and adipogenic differentiation in bone marrow stromal ceils of ovariectomized rats, and to provide an experimental evidence for the mechanism of EFs on treating postmenopausal osteoporosis. Methods： Bone marrow stromal cells from ovariectomized rats were separated and cultivated in the condition of osteoinductive medium or liquid medium for 15 days. Low- （1 μg/mL）, medium- （10 μg/mL） and high- （100 μg/mL） dose EFs were administrated correspondingly. Alkaline phosphatase （ALP） staining, ALP activity determination, oil red O staining and real- time polymerese chain reaction （RT-PCR） were used to determine the effect of EFs on osteogenic differentiation and adipogenic differentiation in bone marrow stromal cells of ovariectomized rats. Moreover, in order to explore the mechanism of EFs on osteogenic differentiation and adipogenic differentiation in bone marrow stromal cells of ovariectomized rats, Dickkopf-related protein 1 （DKK1） was used in the medium group. Enzyme linked immunosorbent assay （ELISA） and RT-PCR were used to determine mRNA levels of 13-catenin, low density lipoprotein receptor-related protein 5 （LRP5） and T cell factor （TCF） protein, known as wnt/β-catenin signal pathway related factors. Results： EFs increased mRNA expression levels of ALP and early osteoblast differentiation factors, such as runt-related transcription factor 2 （Runx2）, osteocaicin and collagen I, and decreased mRNA expression levels of fat generation factors, such as peroxisome proliferator activated receptor gamma 2 （PPAR r/-2） and CCAAT enhancer-binding protein-α （C/EBP α） in a dose-dependent manner. While osteobiast differentiation factors were down-regulated, fat generation factors were up-regulated when DKK1 was applied. Also EFs up-regulated mRNA expression levels of β-catenin, LRP5 and展开更多
Mesenchymal stem cells （MSCs） are characterized by their self-renewing capacity and differentiation potential into multiple tissues. Thus, management of the differentiation capacities of MSCs is important for MSC-ba...Mesenchymal stem cells （MSCs） are characterized by their self-renewing capacity and differentiation potential into multiple tissues. Thus, management of the differentiation capacities of MSCs is important for MSC-based regenerative medicine, such as craniofacial bone regeneration, and in new treatments for metabolic bone diseases, such as osteoporosis. In recent years, histone modification has been a growing topic in the field of MSC lineage specification, in which the Su（var）3-9, enhancer-of-zeste, trithorax （SET） domain-containing family and the Jumonji C （JmjC） domain-containing family represent the major histone lysine methyltransferases （KMTs） and histone lysine demethylases （KDMs）, respectively. In this review, we summarize the current understanding of the epigenetic mechanisms by which SET domain-containine KMTs and JmiC domain-containinlz KDMs balance the osteogenic and adipogenic differentiation of MSCs.展开更多
Background: Intramuscular fat(IMF) content is a vital parameter for assessing pork quality. Increasing evidence has shown that microRNAs(miRNAs) play an important role in regulating porcine IMF deposition. Here, a nov...Background: Intramuscular fat(IMF) content is a vital parameter for assessing pork quality. Increasing evidence has shown that microRNAs(miRNAs) play an important role in regulating porcine IMF deposition. Here, a novel miRNA implicated in porcine IMF adipogenesis was found, and its effect and regulatory mechanism were further explored with respect to intramuscular preadipocyte proliferation and differentiation.Results: By porcine adipose tissue miRNA sequencing analysis, we found that miR-146a-5p is a potential regulator of porcine IMF adipogenesis. Further studies showed that miR-146a-5p mimics inhibited porcine intramuscular preadipocyte proliferation and differentiation, while the miR-146a-5p inhibitor promoted cell proliferation and adipogenic differentiation. Mechanistically, miR-146a-5p suppressed cell proliferation by directly targeting SMAD family member 4(SMAD4) to attenuate TGF-β signaling. Moreover, miR-146a-5p inhibited the differentiation of intramuscular preadipocytes by targeting TNF receptor-associated factor 6(TRAF6) to weaken the AKT/mTORC1 signaling downstream of the TRAF6 pathway.Conclusions: MiR-146a-5p targets SMAD4 and TRAF6 to inhibit porcine intramuscular adipogenesis by attenuating TGF-β and AKT/mTORC1 signaling, respectively. These findings provide a novel miRNA biomarker for regulating intramuscular adipogenesis to promote pork quality.展开更多
基金The reported work was supported in part by research grants from the National Institutes of Health(CA226303,DE020140 to TCH and RRR)the U.S.Department of Defense(OR130096 to JMW)+5 种基金the Scoliosis Research Society(TCH and MJL)the Scoliosis Research Society(TCH and MJL)the National Key Research and Development Program of China(2016YFC1000803 and 2011CB707906).This project was also supported in part by The University of Chicago Cancer Center Support Grant(P30CA014599)and the National Center for Advancing Translational Sciences of the National Institutes of Health through Grant Number UL1 TR000430.SM and MP were supported by the Summer Research Program of The University of Chicago Pritzker School of Medicine.TCH was also supported by the Mabel Green Myers Research Endowment Fund and The University of Chicago Orthopaedic Alumni Fund.Funding sources were not involved in the study designin the collection,analysis and interpretation of datain the writing of the reportand in the decision to submit the paper for publication.
文摘Although bone morphogenetic proteins(BMPs)initially showed effective induction of ectopic bone growth in muscle,it has since been determined that these proteins,as members of the TGF-b superfamily,play a diverse and critical array of biological roles.These roles include regulating skeletal and bone formation,angiogenesis,and development and homeostasis of multiple organ systems.Disruptions of the members of the TGF-b/BMP superfamily result in severe skeletal and extra-skeletal irregularities,suggesting high therapeutic potential from understanding this family of BMP proteins.Although it was once one of the least characterized BMPs,BMP9 has revealed itself to have the highest osteogenic potential across numerous experiments both in vitro and in vivo,with recent studies suggesting that the exceptional potency of BMP9 may result from unique signaling pathways that differentiate it from other BMPs.The effectiveness of BMP9 in inducing bone formation was recently revealed in promising experiments that demonstrated efficacy in the repair of critical sized cranial defects as well as compatibility with bone-inducing bio-implants,revealing the great translational promise of BMP9.Furthermore,emerging evidence indicates that,besides its osteogenic activity,BMP9 exerts a broad range of biological functions,including stem cell differentiation,angiogenesis,neurogenesis,tumorigenesis,and metabolism.This review aims to summarize our current understanding of BMP9 across biology and the body.
基金Supported by the National Natural Science Foundation ofChina(No.81173417No.30901982No.81373656)
文摘OBJECTIVE： To investigate the effects of Huogu I formula on regulation of lipid metabolism in ste- roid-induced osteonecrosis of the femoral head （SONFH） rats and verify our hypothesis that Huogu I formula regulates lipid metabolism by down-regulating peroxisome proliferator-activated receptor gamma （PPARy） expression and activating Wnt signaling pathways. METHODS： Eighty-five rats were divided into four groups： control, model, Huogu 15 g/kg and Huogu 30 g/kg. Six weeks later, animals were anaesthe- tized, femora were dissected for histopathologicalexamination of the osteonecrotic changes and re- pair processes, micro computed tomography （Mi- cro-CT）-based micro-angiography was performed to assess vascularization. Serum lipid levels were detected by haematological examination. The ex- pressions of PPARy, Wnt3a, low density lipoprotein receptor-related protein 5 （LRP5） and 13-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 ~ formula treatment groups. By micro-CT quantification, Huogu ~ formula treat- ment 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 ex- pression of PPARy and increase the expressions of Wnt3a, LRP5 and 13-catenin at both protein and mRNA levels. CONCLUSION： The results of our present study highlight the lipid-lowering potential of Huogu Ⅰ formula, and provide further evidence of the in- volvement of the PPARy inhibition and Wnt/LRPS/ 13-catenin signaling activation in the effects of Huogu Ⅰ formula.
基金Supported by Grants from the National Research of Foundation of the South Korea,No.2012M3A9C7050101,No.2011-0030028 and No.2006-2004112
文摘Adipose tissue is a major metabolic organ, and it has been traditionally classified as either white adipose tissue(WAT) or brown adipose tissue(BAT). WAT and BAT are characterized by different anatomical locations, morphological structures, functions, and regulations. WAT and BAT are both involved in energy balance. WAT is mainly involved in the storage and mobilization of energy in the form of triglycerides, whereas BAT specializes in dissipating energy as heat during cold- or diet-induced thermogenesis. Recently, brownlike adipocytes were discovered in WAT. These brownlike adipocytes that appear in WAT are called beige or brite adipocytes. Interestingly, these beige/brite cells resemble white fat cells in the basal state, but they respond to thermogenic stimuli with increased levels of thermogenic genes and increased respiration rates. In addition, beige/brite cells have a gene expressionpattern distinct from that of either white or brown fat cells. The current epidemic of obesity has increased the interest in studying adipocyte formation(adipogenesis), especially in beige/brite cells. This review summarizes the developmental process of adipose tissues that originate from the mesenchymal stem cells and the features of these three different types of adipocytes.
文摘Objective： To observe the function of wnt/β-catenin signal pathway on the process that epimedium-derived flavonoids （EFs） regulate the balance between osteogenic differentiation and adipogenic differentiation in bone marrow stromal ceils of ovariectomized rats, and to provide an experimental evidence for the mechanism of EFs on treating postmenopausal osteoporosis. Methods： Bone marrow stromal cells from ovariectomized rats were separated and cultivated in the condition of osteoinductive medium or liquid medium for 15 days. Low- （1 μg/mL）, medium- （10 μg/mL） and high- （100 μg/mL） dose EFs were administrated correspondingly. Alkaline phosphatase （ALP） staining, ALP activity determination, oil red O staining and real- time polymerese chain reaction （RT-PCR） were used to determine the effect of EFs on osteogenic differentiation and adipogenic differentiation in bone marrow stromal cells of ovariectomized rats. Moreover, in order to explore the mechanism of EFs on osteogenic differentiation and adipogenic differentiation in bone marrow stromal cells of ovariectomized rats, Dickkopf-related protein 1 （DKK1） was used in the medium group. Enzyme linked immunosorbent assay （ELISA） and RT-PCR were used to determine mRNA levels of 13-catenin, low density lipoprotein receptor-related protein 5 （LRP5） and T cell factor （TCF） protein, known as wnt/β-catenin signal pathway related factors. Results： EFs increased mRNA expression levels of ALP and early osteoblast differentiation factors, such as runt-related transcription factor 2 （Runx2）, osteocaicin and collagen I, and decreased mRNA expression levels of fat generation factors, such as peroxisome proliferator activated receptor gamma 2 （PPAR r/-2） and CCAAT enhancer-binding protein-α （C/EBP α） in a dose-dependent manner. While osteobiast differentiation factors were down-regulated, fat generation factors were up-regulated when DKK1 was applied. Also EFs up-regulated mRNA expression levels of β-catenin, LRP5 and
基金supported by the National Institute of Dental and Craniofacial Research grants, K08DE024603-02, DE019412, and DE01651a grant from 111 Project of MOE, Chinasupported by Open Fund of State Key Laboratory of Oral Diseases, Sichuan University
文摘Mesenchymal stem cells （MSCs） are characterized by their self-renewing capacity and differentiation potential into multiple tissues. Thus, management of the differentiation capacities of MSCs is important for MSC-based regenerative medicine, such as craniofacial bone regeneration, and in new treatments for metabolic bone diseases, such as osteoporosis. In recent years, histone modification has been a growing topic in the field of MSC lineage specification, in which the Su（var）3-9, enhancer-of-zeste, trithorax （SET） domain-containing family and the Jumonji C （JmjC） domain-containing family represent the major histone lysine methyltransferases （KMTs） and histone lysine demethylases （KDMs）, respectively. In this review, we summarize the current understanding of the epigenetic mechanisms by which SET domain-containine KMTs and JmiC domain-containinlz KDMs balance the osteogenic and adipogenic differentiation of MSCs.
基金supported by grants from the National Natural Science Foundation (31872979, 31572366)the National Key Research and Development Program of China (2017YFD0502002)the National Basic Research Programs of China (2015CB943102)。
文摘Background: Intramuscular fat(IMF) content is a vital parameter for assessing pork quality. Increasing evidence has shown that microRNAs(miRNAs) play an important role in regulating porcine IMF deposition. Here, a novel miRNA implicated in porcine IMF adipogenesis was found, and its effect and regulatory mechanism were further explored with respect to intramuscular preadipocyte proliferation and differentiation.Results: By porcine adipose tissue miRNA sequencing analysis, we found that miR-146a-5p is a potential regulator of porcine IMF adipogenesis. Further studies showed that miR-146a-5p mimics inhibited porcine intramuscular preadipocyte proliferation and differentiation, while the miR-146a-5p inhibitor promoted cell proliferation and adipogenic differentiation. Mechanistically, miR-146a-5p suppressed cell proliferation by directly targeting SMAD family member 4(SMAD4) to attenuate TGF-β signaling. Moreover, miR-146a-5p inhibited the differentiation of intramuscular preadipocytes by targeting TNF receptor-associated factor 6(TRAF6) to weaken the AKT/mTORC1 signaling downstream of the TRAF6 pathway.Conclusions: MiR-146a-5p targets SMAD4 and TRAF6 to inhibit porcine intramuscular adipogenesis by attenuating TGF-β and AKT/mTORC1 signaling, respectively. These findings provide a novel miRNA biomarker for regulating intramuscular adipogenesis to promote pork quality.
