骨形态发生蛋白和糖尿病及其并发症之间的关系

骨形态发生蛋白（BMPs）是转化生长因子?β（TGF-β）超家族的成员,具有多种生理功能,如胚胎形成、骨代谢、造血作用以及神经形成等。近年来研究发现,BMPs还与糖、脂类及能量代谢密切相关,并参与糖尿病及其并发症如糖尿病性肾病、糖尿病视网膜病变、糖尿病血管病变等过程的调节。同时BMPs可以从代谢角度调节糖尿病型肥胖的发生,为未来糖尿病的治疗提供了新的思路。     

骨形态发生蛋白与血管钙化研究进展

近年血管钙化的细胞分子机制研究结果表明,血管钙化形成过程是一个与骨发育相似的,主动的,可预防和可逆转的高度可调控的生物学过程。1965年Urist发现骨形态发生蛋白（bonemorphogeneticproteins,BMPs）．到目前为止,已发现30余种成员,其中以BMP-2的作用最为重要。它们是一类唯一能够单独诱导骨组织形成的局部生长因子,     

铁调素与骨形态发生蛋白相互关系的研究进展

临床和实验研究均表明铁过载能引起骨质疏松,铁调素(hepcidin)是近年发现的调节体内铁代谢的关键因子,骨形态发生蛋白(bone morphegenetic proteins,BMPs)能上调铁调素的表达,提示BMPs在骨质疏松的恢复中起重要作用。本文对BMPs和铁调素关系的研究进展进行综述,以期为研究铁过载引起的骨质疏松及其治疗提供基础。     

骨形态发生蛋白2在肺癌组织中的表达和意义

目的探讨骨形态发生蛋白2（BMP-2）在肺癌组织中的表达。方法采用免疫组化SP法检测60例肺癌组织和10例正常肺组织中BMP-2的蛋白表达,并进行相关分析。结果 BMP-2在肺癌组织中的阳性表达为67%,正常肺组织无阳性表达,P〈0.01。BMP-2蛋白表达与淋巴结的转移、临床分期有关。结论 BMP-2在肺癌的发生发展及转移中可能有重要作用。     

骨形态发生蛋白与骨代谢

骨形态发生蛋白(BMPs)是多功能细胞因子,其家庭成员参与骨骼形成、分化、吸收等过程,对成骨细胞、破骨细胞和软骨细胞均有不同程度的影响。本文就BMPs对成骨细胞、破骨细胞及软骨细胞作用的研究进展进行综述。     

结缔组织生长因子与骨形成蛋白-9在骨代谢中的研究进展

<正>结缔组织生长因子(CTGF)是一种细胞外基质分泌蛋白,生理状态下,在心、脑、肝、肾等组织器官中呈基础量表达,病理状态下,如在某些增生性或纤维性疾病中,CTGF过度表达与疾病的发生发展紧密相关。CTGF调节细胞功能多样化,参与体内多种病理生理过程,如胚胎发育、雌性生殖系统、恶性肿瘤、纤维化疾病等。CTGF是骨形态发生蛋白(BMPs)信号通路的靶基因,可作用于BMPs信号通路〔1〕,而BMP-9是已知BMPs中     

重组骨形态发生蛋白7基因转染骨髓间充质干细胞及其在该细胞中的表达

目的将重组骨形态发生蛋白7质粒（pcDNA3．1-BMP7）转染至体外培养的兔骨髓间充质干细胞中．测定骨形态发生蛋白7基因在该细胞中的表达。方法骨形态发生蛋白7基因序列测定、拼接后与报道的骨形态发生蛋白7基因序列对照：脂质体介导pcDNA3．1-BMP7转染骨髓间充质干细胞，G418筛选14d，Western blot、PCR、原位杂交检测骨形态发生蛋白7基因的表达。结果序列测定证实与GenBank报道的骨形态发生蛋白7全长基因序列一致：转染pcDNA3．1-BMP7质粒的骨髓间充质干细胞有大量骨形态发生蛋白7蛋白及骨态发生蛋白7 mRNA表达。结论脂质体介导下，重组真核表达载体pcDNA3．1-BMP7能被转入骨髓间充质干细胞．且表达了骨形态发生蛋白7及骨形态发生蛋白7 mRNA。     

骨形成蛋白2,4在胃黏膜疾病中的表达及意义

骨形成蛋白（bone morphogenetic、proteins，BMPs）构成了一个结构功能相似的多肽因子家族，除BMP-1外同为转化生长因子β（TGF—β）超家族的成员。近期研究表明BMPs除了可在异位诱导骨、软骨形成外，对靶细胞的生长、分化及凋亡，对机体胚胎发育的全过程都发挥着重要的作用。此外，还发现BMPs不仅与部分骨肿瘤的发生、发展密切相关，还与涎腺、前列腺和卵巢肿瘤等上皮性肿瘤的生物学行为有关。但BMP与胃肠道疾病苊其是胃黏膜疾病发生、发展的关系尚不明了：为此，本研究采用免疫组化及原位杂交的方法检测BMP-2，4在不同类型胃黏膜疾患中蛋白质和mRNA表达，探讨其与临床病理参数之间的关系，     

骨形态发生蛋白微球对犬骨髓基质细胞增殖和分化的影响

目的观察骨形态发生蛋白微球对犬骨髓基质细胞（MSC）增殖及分化的影响。方法聚乳酸聚乙醇酸共聚物制备微球,采用细胞培养及组织化学等方法观察骨形态发生蛋白载药微球对犬MSC增殖、分化及Ⅰ型胶原表达的影响。结果骨形态发生蛋白微球对MSC的增殖无明显影响,但对细胞的分化功能及Ⅰ型胶原表达有明显的促进作用。结论骨形态发生蛋白能够提高MSC的体外成骨能力,且微球可作为骨形态发生蛋白的良好载体。     

骨形态发生蛋白4与血管钙化的相关性

骨形态发生蛋白4(BMP-4)是转化生长因子β(TGF-β)超家族成员之一,属于多功能生长因子,在胚胎发育、血管生成、细胞增殖、分化、骨骼形成、异位成骨、骨折修复等方面具有重要作用。血管钙化(VC)是一个与骨发育相似的可调控的复杂的生物学过程,其中心环节是血管平滑肌细胞(VSMC)向成骨样细胞转化。近年的研究发现,BMP-4可能参与血管钙化的发生和发展,但具体机制尚未清楚,文章就其相关关系的研究进展作一综述。     

Bone morphogenetic proteins in vascular calcification

Vascular calcification is a common problem among the elderly and those with chronic kidney disease (CKD) and diabetes. The process of tunica media vascular calcification in CKD appears to involve a phenotypic change in the vascular smooth muscle cell (VSMC) resulting in cell-mediated mineralization of the extracellular matrix. The bone morphogenetic proteins (BMPs) are important regulators in orthotopic bone formation, and their localization at sites of vascular calcification raises the question of their role. In this review, we will discuss the actions of the BMPs in vascular calcification. Although the role of BMP-2 in vascular calcification is not proven, it has been the most studied member of the BMP family in this disease process. The role of BMP-2 may be through inducing osteoblastic differentiation of VSMCs through induction of MSX-2, or by inducing apoptosis of VSMCs, a process thought critical in the initiation of vascular calcification. Additionally, BMP-2 may be related to loss of regulation of the matrix Gla protein. A second BMP, BMP-7, less studied than BMP-2 may have opposing actions in vascular calcification. In postnatal life, BMP-7 is expressed primarily in the kidney, and expression is diminished by renal injury. BMP-7 is an important regulator of skeletal remodeling and the VSMC phenotype. BMP-7 restores skeletal anabolic balance in animal models of CKD with disordered skeletal modeling, also reducing serum phosphate in the process. BMP-7 also reverses vascular calcification in CKD, and reduction in vascular calcification is due, in part, to reduced serum phosphate, an important inducer of VSMC-mediated vascular mineralization and in part to direct actions on the VSMC.     

Beyond the bone: Bone morphogenetic protein signaling in adipose tissue

The bone morphogenetic proteins (BMPs) belong to the same superfamily as related to transforming growth factor β (TGFβ), growth and differentiation factors (GDFs), and activins. They were initially described as inducers of bone formation but are now known to be involved in morphogenetic activities and cell differentiation throughout the body, including the development of adipose tissue and adipogenic differentiation. BMP4 and BMP7 are the most studied BMPs in adipose tissue, with major roles in white adipogenesis and brown adipogenesis, respectively, but other BMPs such as BMP2, BMP6, and BMP8b as well as some inhibitors and modulators have been shown to also affect adipogenesis. It has become ever more important to understand adipose regulation, including the BMP pathways, in light of the strong links between obesity and metabolic and cardiovascular disease. In this review, we summarize the available information on BMP signaling in adipose tissue using preferentially articles that have appeared in the last decade, which together demonstrate the importance of BMP signaling in adipose biology.     

Bone Morphogenetic Proteins im Skelettsystem—

Bone morphogenetic proteins (BMPs) belong to the transforming growth factor-beta superfamily. Their potential for organ and tissue regeneration and repair has been intensively investigated in recent years. Studies on fetal development have demonstrated the important role of these proteins for the development and differentiation of different organs. Miss-expression or mutation of BMPs may lead to severe abnormalities or even abortion. However, a regenerative potential has also been recognized for the adult organism. BMPs support fracture healing and may contribute to treatment of joint diseases. Thus, BMP-7 is one of the first BMPs approved for clinical application in non-unions of bone fractures resistant to conventional therapy. In degenerative and inflammatory joint diseases, experimental data suggest a decrease of BMP expression in cartilage tissue. Therefore, BMPs could be promising therapeutic candidates in these diseases, although more detailed analyses are necessary. In this review we will focus on bone morphogenetic proteins and discuss present and putative future clinical applications.     

Cell differentiation in vascular calcification

Summary Ectopic tissue formation is commonly found in calcified atherosclerotic plaques. This suggests that cell differentiation plays an important role in vascular calcification, even though the origin of the cells involved is unclear. Calcifying vascular cells (CVCs), derived from bovine aortic media, have been used as an in vitro model for vascular calcification. CVCs have many characteristics in common with bone cells, but there are also differences suggesting mechanisms that may be applicable to the problem of osteoporosis in the setting of vascular calcification. Matrix GLA protein (MGP) deficient mice develop severe vascular calcification and die prematurely from heart failure and/or aortic rupture. The molecular mechanism of MGP is unknown. It has been hypothesized that MGP acts as a calcification inhibitor by binding calcium, preventing mineral deposition in extracelular fluids near the saturation point for calcium and phosphate. Alternatively, MGP expression may be an attempt to regulate cell differentiation in the vascular wall, possibly by acting as an inhibitor to a factor able to induce cartilage and bone such as bone morphogenetic proteins (BMPs).     

Bone morphogenetic proteins and their antagonists

Skeletal homeostasis is determined by systemic hormones and local factors. Bone morphogenetic proteins (BMPs) are unique because they induce the commitment of mesenchymal cells toward cells of the osteoblastic lineage and also enhance the differentiated function of the osteoblast. BMP activities in bone are mediated through binding to specific cell surface receptors and through interactions with other growth factors. BMPs are required for skeletal development and maintenance of adult bone homeostasis, and play a role in fracture healing. BMPs signal by activating the mothers against decapentaplegic (Smad) and mitogen activated protein kinase (MAPK) pathways, and their actions are tempered by intracellular and extracellular proteins. The BMP antagonists block BMP signal transduction at multiple levels including pseudoreceptor, inhibitory intracellular binding proteins, and factors that induce BMP ubiquitination. A large number of extracellular proteins that bind BMPs and prevent their binding to signaling receptors have emerged. The extracellular antagonists are differentially expressed in cartilage and bone tissue and exhibit BMP antagonistic as well as additional activities. Both intracellular and extracellular antagonists are regulated by BMPs, indicating the existence of local feedback mechanisms to modulate BMP cellular activities. This work was supported by Grant AR21707 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases.     

骨形成蛋白与支气管哮喘

骨形成蛋白参与多种组织的纤维化进程,包括调节炎症反应,调控细胞的增殖与凋亡、纤维化、细胞外基质沉积及上皮一间质转化,诱导成纤维细胞表型转化。其信号经Smad通路转导。Gremlin是一种骨形成蛋白拮抗剂,可以阻碍骨形成蛋白与其受体的结合,抑制Smad蛋白磷酸化。本文旨在探讨骨形成蛋白及其拮抗剂gremlin在支气管哮喘中的分布及作用,阐述Smad信号通路及其与其他信号转导途径的联系,为支气管哮喘发病机制的研究及治疗提供新的思路。     

Analysis of spatial and temporal expression patterns of bone morphogenetic protein family members in the rat uterus over the estrous cycle

Recent studies have demonstrated that bone morphogenetic proteins (BMPs) play fundamental roles in female fertility. This is particularly evident in terms of the ovary. One major question that is just beginning to be addressed is the role of BMPs in the non-pregnant uterus. To help fill this gap, we used in situ hybridization to investigate the expression of BMP family members in the rat uterus over the estrous cycle. We found that the endometrial/uterine cycle is accompanied by the expression of several components of the BMP pathway - including ligands, receptors and antagonists. The mRNAs encoding BMP receptors are expressed in the epithelial (BMP-RIA, -RIB and -RII), periluminal stroma (BMP-RIA and -RII) and smooth muscle cells (BMP-RIA and -RII). The expression of all three receptors showed clear cyclic variations. The mRNAs encoding BMP ligands were highly expressed in the periluminal stroma (BMP-2 and -7) and glandular epithelium (BMP-7). The expression of BMP-2, but not BMP-7, was cyclical. Notably, the periluminal stroma expressed noggin mRNA. In the blood vascular system, BMP-4, -6 and -RII mRNAs were expressed in myometrial endothelial cells. Interestingly, follistatin, noggin, and BMP-4, -6 and -7 mRNAs were expressed in eosinophilic leukocytes, suggesting unexpected roles for eosinophil-derived BMPs in uterine function. We conclude that BMP ligands, receptors and antagonists are expressed in spatially and temporally restricted patterns that are consistent with a physiological role for these regulatory molecules in promoting uterine cellular processes including cell proliferation, differentiation and apoptosis during the cycle.     

Osteogenin and recombinant bone morphogenetic protein 2B are chemotactic for human monocytes and stimulate transforming growth factor beta 1 mRNA expression.

Subcutaneous implantation of demineralized bone matrix initiates a sequence of developmental events, which culminate in endochondral bone formation. During early stages of development of matrix-induced implants, ED1, Ia-positive monocytes-macrophages were observed, suggesting that in the initial phases of the endochondral bone formation cascade, the bone-inductive protein osteogenin and related bone morphogenetic proteins (BMPs) might serve as potent chemoattractants to recruit circulating monocytes. In this investigation, we demonstrate that at concentrations of 10-100 fg/ml (0.3-3 fM), native bovine osteogenin and recombinant human BMP-2B (rhBMP-2B) induce the directed migration of human blood monocytes in vitro. This chemotactic response was associated with expression of BMP binding sites (receptors) on monocytes. About 750 receptors per cell were detected with an apparent dissociation constant of 200 pM. Both osteogenin and rhBMP-2B at higher concentrations (0.1-30 ng/ml) stimulated mRNA expression for an additional regulatory molecule, type beta 1 transforming growth factor (TGF-beta 1) in human monocytes. TGF-beta 1, in turn, is known to induce a cascade of events leading to matrix generation. Monocytes stimulated by TGF-beta are known to secrete a number of chemotactic and mitogenic cytokines that recruit endothelial and mesenchymal cells and promote their synthesis of collagen and associated matrix constituents. TGF-beta 1 in concert with these other cytokines and matrix components regulates chemotaxis, mesenchymal proliferation, differentiation, angiogenesis, and controlled synthesis of extracellular matrix. Our results demonstrate that osteogenin and related BMPs through their profound effects on monocyte recruitment and cytokine synthesis may promote additional successive steps in the endochondral bone formation cascade.