The bone morphogenetic protein(BMP)gene family comprises a group of multifunctional cytokines that play important roles in limb development,bone formation,fat deposition,and reproductive traits of vertebrates.However,...The bone morphogenetic protein(BMP)gene family comprises a group of multifunctional cytokines that play important roles in limb development,bone formation,fat deposition,and reproductive traits of vertebrates.However,no systematic and comprehensive investigations of the various traits of the whole family members have been conducted,particularly in chickens.Here,we performed genome-wide screening and identified 14 BMP genes,which were classified into the BMP2/4,BMP5/6/7/8A,growth differentiation factor(GDF)2/BMP10,GDF5/6/7,and GDF11/BMP3/15 subfamilies.Genetic variation pattern analysis showed that BMP genes were responsible for the artificial selection of commercial broilers and layers,with BMP2,BMP6,and GDF7 likely contributing significantly to the formation of both specialized meat-and eggtype lines,whereas BMP7 likely contributed more to the formation of meat-type lines.Genetic association analysis showed that single nucleotide polymorphisms(SNPs)in the BMP7 intron region were associated with body weight,breast muscle weight,leg weight,abdominal fat weights and contents of total cholesterol(T-CHO),triglyceride(TG),low-density lipoprotein(LDL),and high-density lipoprotein(HDL)in serum.Additionally,gain-and loss-of-function assays demonstrated that BMP7 promoted the proliferation,myogenic differentiation,and lipid droplet accumulation in myoblasts;enhanced lipid synthesis in hepatocytes;promoted the proliferation and inhibited adipogenic differentiation of intramuscular preadipocytes;and induced the proliferation and adipogenic differentiation of abdominal preadipocytes.These results provide novel insights into the role of BMP genes in chicken growth,reproductive regulation,and lipid deposition and could be used to develop genetic markers for breeding selection in chickens.展开更多
The transforming growth factor-β(TGF-β)and bone morphogenetic protein(BMP)signaling pathways are pivotal regulators of cellular processes,playing indispensable roles in embryogenesis,postnatal development,and tissue...The transforming growth factor-β(TGF-β)and bone morphogenetic protein(BMP)signaling pathways are pivotal regulators of cellular processes,playing indispensable roles in embryogenesis,postnatal development,and tissue homeostasis.These pathways are particularly critical within the skeletal system,as they coordinate osteogenesis,chondrogenesis,and bone remodeling through intricate molecular mechanisms.TGF-β/BMP signaling is primarily transduced via canonical Smad-dependent pathways(e.g.,ligands,receptors,and intracellular Smads)and the non-canonical Smad-independent(e.g.,p38 mitogen-activated protein kinase,MAPK)cascade.Both pathways converge on master transcriptional regulators,including Runx2 and Osterix,and their precise coordination is indispensable for skeletal development,maintenance,and repair.The dysregulation of TGF-β/BMP signaling contributes to a spectrum of skeletal dysplasia and bone pathologies.Advances in molecular genetics,particularly gene-targeting strategies and transgenic mouse models,have deepened our understanding of the spatiotemporal control of TGF-β/BMP signaling in bone and cartilage development.Moreover,emerging research underscores extensive crosstalk between TGF-β/BMP and other critical pathways,such as Wnt/β-catenin,mitogen-activated protein kinase(MAPK),parathyroid hormone(PTH)/PTH-related protein(PTHrP),fibroblast growth factors(FGF),Hedgehog,Notch,insulin-like growth factors(IGF)/insulin-like growth factors receptor(IGFR),Mammalian target of rapamycin(mTOR),and autophagy,forming an integrated regulatory network that ensures skeletal integrity.Our review synthesizes the current knowledge on the molecular components,regulatory mechanisms,and functional integration of TGF-β/BMP signaling in skeletal biology,with an emphasis on its roles in development,regeneration,and disease.By elucidating the molecular underpinnings of TGF-β/BMP pathways and their contextual interactions,we aim to highlight translational opportunities and novel therapeutic strategies for treating skeletal disorders.展开更多
目的基于大鼠骨形态发生蛋白2(bone morphogenetic protein2,BMP2)/Smad家族成员1(smad family member 1,Smad1)通路,探究重组人转化生长因子-β1(recombinant human transforming growth factor-β1,rhTGF-β1)对正畸牙移动(orthodonti...目的基于大鼠骨形态发生蛋白2(bone morphogenetic protein2,BMP2)/Smad家族成员1(smad family member 1,Smad1)通路,探究重组人转化生长因子-β1(recombinant human transforming growth factor-β1,rhTGF-β1)对正畸牙移动(orthodontic tooth movement,OMT)大鼠破骨细胞形成的影响。方法构建大鼠OTM模型,采用显微CT(Micro-CT)分析测定OTM的距离;通过抗酒石酸酸性磷酸酶(tartrate-resistant acid phosphatase,TRAP)染色评估压力侧破骨细胞活性;苏木精-伊红(hematoxylin and eosin,HE)染色评估压力侧组织形态学特征,免疫组化(immunohistochemistry,IHC)染色和蛋白质印迹(Western blot)测定相关蛋白表达水平。结果与正常组相比,Model组大鼠OTM距离增加(P<0.01),牙周间隙明显变窄并出现吸收陷窝,压力侧的基质金属蛋白酶-9(matrix metalloproteinases-9,MMP-9)、核因子κB受体活化因子配体(receptor activator of nuclear factor kappa B ligand,RANKL)增加(P<0.01)、骨保护素(osteoprotegerin,OPG)表达降低(P<0.01),BMP2/Smad1信号通路被激活(P<0.01)。经BMP2抑制剂Noggin处理后,与Model组相比,BMP2、p-Smad1表达显著降低(P<0.01),OTM距离显著降低(P<0.01),且压力侧的TRAP、MMP-9及RANKL表达均显著降低(P<0.01),OPG升高(P<0.01)。经rhTGF-β1处理的大鼠中,较Model组OTM距离显著增加(P<0.01),TRAP阳性多核细胞数量升高(P<0.01),压力侧的MMP-9及RANKL表达均显著升高(P<0.05)、OPG表达显著降低(P<0.01),且BMP2、p-Smad1表达上调(P<0.01)。此外,rhTGF-β1+Noggin组部分逆转了rhTGF-β1组大鼠的破骨细胞数量的增加效应(P<0.01)。结论正畸力可促进破骨细胞形成,且rhTGF-β1可通过BMP2/Smad1信号通路增强OTM过程中破骨细胞的形成。展开更多
基金supported by the National Natural Science Foundation of China(32272867,32372871 and 32172720)the National Key Research and Development Program of China(2022YFF1000202)。
文摘The bone morphogenetic protein(BMP)gene family comprises a group of multifunctional cytokines that play important roles in limb development,bone formation,fat deposition,and reproductive traits of vertebrates.However,no systematic and comprehensive investigations of the various traits of the whole family members have been conducted,particularly in chickens.Here,we performed genome-wide screening and identified 14 BMP genes,which were classified into the BMP2/4,BMP5/6/7/8A,growth differentiation factor(GDF)2/BMP10,GDF5/6/7,and GDF11/BMP3/15 subfamilies.Genetic variation pattern analysis showed that BMP genes were responsible for the artificial selection of commercial broilers and layers,with BMP2,BMP6,and GDF7 likely contributing significantly to the formation of both specialized meat-and eggtype lines,whereas BMP7 likely contributed more to the formation of meat-type lines.Genetic association analysis showed that single nucleotide polymorphisms(SNPs)in the BMP7 intron region were associated with body weight,breast muscle weight,leg weight,abdominal fat weights and contents of total cholesterol(T-CHO),triglyceride(TG),low-density lipoprotein(LDL),and high-density lipoprotein(HDL)in serum.Additionally,gain-and loss-of-function assays demonstrated that BMP7 promoted the proliferation,myogenic differentiation,and lipid droplet accumulation in myoblasts;enhanced lipid synthesis in hepatocytes;promoted the proliferation and inhibited adipogenic differentiation of intramuscular preadipocytes;and induced the proliferation and adipogenic differentiation of abdominal preadipocytes.These results provide novel insights into the role of BMP genes in chicken growth,reproductive regulation,and lipid deposition and could be used to develop genetic markers for breeding selection in chickens.
基金supported by grants by National Natural Science Foundation of China(No.82571024,No.81400489)Zhejiang Provincial Natural Science Foundation of China(LZ23H140001,LTGY23H200006,LGC22H200012)+3 种基金Zhejiang Qianjiang Talent Program(21040040-E)the Fundamental Research Funds of Zhejiang Sci-Tech University(2021Q031)Zhejiang Jiaxing Science Technology Foundation(2023AZ31004,2023AY11045,2023AY31012,2020AY10001)Zhejiang Drug&Health Foundation(2022507032,2023KY340)。
文摘The transforming growth factor-β(TGF-β)and bone morphogenetic protein(BMP)signaling pathways are pivotal regulators of cellular processes,playing indispensable roles in embryogenesis,postnatal development,and tissue homeostasis.These pathways are particularly critical within the skeletal system,as they coordinate osteogenesis,chondrogenesis,and bone remodeling through intricate molecular mechanisms.TGF-β/BMP signaling is primarily transduced via canonical Smad-dependent pathways(e.g.,ligands,receptors,and intracellular Smads)and the non-canonical Smad-independent(e.g.,p38 mitogen-activated protein kinase,MAPK)cascade.Both pathways converge on master transcriptional regulators,including Runx2 and Osterix,and their precise coordination is indispensable for skeletal development,maintenance,and repair.The dysregulation of TGF-β/BMP signaling contributes to a spectrum of skeletal dysplasia and bone pathologies.Advances in molecular genetics,particularly gene-targeting strategies and transgenic mouse models,have deepened our understanding of the spatiotemporal control of TGF-β/BMP signaling in bone and cartilage development.Moreover,emerging research underscores extensive crosstalk between TGF-β/BMP and other critical pathways,such as Wnt/β-catenin,mitogen-activated protein kinase(MAPK),parathyroid hormone(PTH)/PTH-related protein(PTHrP),fibroblast growth factors(FGF),Hedgehog,Notch,insulin-like growth factors(IGF)/insulin-like growth factors receptor(IGFR),Mammalian target of rapamycin(mTOR),and autophagy,forming an integrated regulatory network that ensures skeletal integrity.Our review synthesizes the current knowledge on the molecular components,regulatory mechanisms,and functional integration of TGF-β/BMP signaling in skeletal biology,with an emphasis on its roles in development,regeneration,and disease.By elucidating the molecular underpinnings of TGF-β/BMP pathways and their contextual interactions,we aim to highlight translational opportunities and novel therapeutic strategies for treating skeletal disorders.
文摘目的基于大鼠骨形态发生蛋白2(bone morphogenetic protein2,BMP2)/Smad家族成员1(smad family member 1,Smad1)通路,探究重组人转化生长因子-β1(recombinant human transforming growth factor-β1,rhTGF-β1)对正畸牙移动(orthodontic tooth movement,OMT)大鼠破骨细胞形成的影响。方法构建大鼠OTM模型,采用显微CT(Micro-CT)分析测定OTM的距离;通过抗酒石酸酸性磷酸酶(tartrate-resistant acid phosphatase,TRAP)染色评估压力侧破骨细胞活性;苏木精-伊红(hematoxylin and eosin,HE)染色评估压力侧组织形态学特征,免疫组化(immunohistochemistry,IHC)染色和蛋白质印迹(Western blot)测定相关蛋白表达水平。结果与正常组相比,Model组大鼠OTM距离增加(P<0.01),牙周间隙明显变窄并出现吸收陷窝,压力侧的基质金属蛋白酶-9(matrix metalloproteinases-9,MMP-9)、核因子κB受体活化因子配体(receptor activator of nuclear factor kappa B ligand,RANKL)增加(P<0.01)、骨保护素(osteoprotegerin,OPG)表达降低(P<0.01),BMP2/Smad1信号通路被激活(P<0.01)。经BMP2抑制剂Noggin处理后,与Model组相比,BMP2、p-Smad1表达显著降低(P<0.01),OTM距离显著降低(P<0.01),且压力侧的TRAP、MMP-9及RANKL表达均显著降低(P<0.01),OPG升高(P<0.01)。经rhTGF-β1处理的大鼠中,较Model组OTM距离显著增加(P<0.01),TRAP阳性多核细胞数量升高(P<0.01),压力侧的MMP-9及RANKL表达均显著升高(P<0.05)、OPG表达显著降低(P<0.01),且BMP2、p-Smad1表达上调(P<0.01)。此外,rhTGF-β1+Noggin组部分逆转了rhTGF-β1组大鼠的破骨细胞数量的增加效应(P<0.01)。结论正畸力可促进破骨细胞形成,且rhTGF-β1可通过BMP2/Smad1信号通路增强OTM过程中破骨细胞的形成。
