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1.
To study the ectopic chondrogenesis in canine mammary mixed tumors, the expression of bone morphogenetic protein-6 (BMP-6) and specific BMP receptors (BMPRs), BMPR-IA, BMPR-IB, and BMPR-II, was examined using immunohistochemical and immunoblot analysis in 39 canine mammary gland tumors. Immunohistochemically, BMP-6 and all three types of BMPRs were coexpressed in the myoepithelial cells and chondrocytes in six of eight benign mixed tumors. In complex adenomas, myoepithelial cells showed an expression pattern of BMP-6, BMPR-IA, and BMPR-II similar to those in benign mixed tumors, whereas immunoreactivity for BMPR-IB was very mild. The myoepithelial cells proliferating within the basement membrane showed more intense immunoreactivity for BMP-6 and all BMPRs as compared with those proliferating in the interstitial areas. Western blotting analysis revealed immunopositive bands at 40-45 kDa for BMP-6 in the samples from simple and complex adenomas and benign mixed tumors. The BMPR-IB-specific bands at 45 kDa were most detected in benign mixed tumors. Because among BMPRs, BMPR-IB is thought to be the major receptor for BMP-6 for primary chondrogenesis, these findings suggest that the expression of BMP and its receptors on the myoepithelial cells might play a role in the ectopic cartilage formation in canine mammary gland tumors, especially in benign mixed tumors.  相似文献   

2.
Enzootic bovine leukosis (EBL) is typically observed in cattle over 3 years old. However, some cases of EBL onset in young beef cattle have been reported in Japan. The mechanism for early EBL onset is unclear. In Japan, beef cattle are given large amounts of concentrated feed with low vitamin A. Bone morphogenetic proteins (BMPs) are regulators of cell proliferation, differentiation, and apoptosis, and thought to represent one of the key players in tumor malignancy. The purpose of this study was to evaluate the differences in BMP-6 methylation status between EBL beef cattle under 3 years old and other cattle. We investigated the methylation status of the BMP-6 promoter region in 32 EBL beef cattle under 3 years old. We also compared the methylation status of EBL dairy cattle to that of healthy cattle. Median methylation rate of the BMP-6 promoter region in EBL beef cattle under 3 years old was 8.9%, which was significantly higher than that of other groups. Hypermethylation of the BMP-6 promoter region might contribute to early onset of EBL in beef cattle under 3 years old, and animal feeding management practices specific to beef cattle may affect the methylation status of the BMP-6 promoter region.  相似文献   

3.
OBJECTIVE: To determine the mRNA expression of bone morphogenetic protein (BMP)-6 and -2 and a BMP antagonist (Noggin) in horses with osteochondrosis. SAMPLE POPULATION: Samples of articular cartilage from affected stifle or shoulder joints of 10 immature horses with naturally acquired osteochondrosis and corresponding joints of 9 clinically normal horses of similar age; additionally, samples of distal femoral growth plate cartilage and distal femoral articular cartilage were obtained from a normal equine fetus. PROCEDURE: Cartilage specimens were snap-frozen in liquid nitrogen, and total RNA was isolated. Adjacent specimens were fixed in 4% paraformaldehyde for histologic examination. Expression of BMP-6, BMP-2, and Noggin mRNA was evaluated by real-time quantitative polymerase chain reaction (PCR) assays. Spatial tissue mRNA expression of BMP-6 was determined by in situ hybridization. RESULTS: Nucleotide sequences were obtained for portions of the BMP-6 propeptide and mature peptide region, as well as the signal and mature peptide region of Noggin. Expression of BMP-6, BMP-2, and Noggin mRNA was found to be similar in cartilage from normal and osteochondrosis-affected horses. Spatial expression of BMP-6 correlated with the middle and deep layers of articular cartilage; no differences were observed in overall expression between cartilage specimens from the 2 groups of horses. No expression of BMP-6 was found in the superficial layer, subchondral bone, or osteochondrosis-affected cleft fibrous tissue. CONCLUSIONS AND CLINICAL RELEVANCE: Although these signaling peptides may play important roles in cartilage differentiation, results did not provide evidence to suggest that they are involved in the disease process of osteochondrosis.  相似文献   

4.
Seventy-three mammary tumors and three mammary tissue specimens were examined to elucidate the expression of bone morphogenetic protein (BMP)-6 in the myoepithelial cells of canine mammary gland tumors. Morphologically, the myoepithelial cells were classified into four types: resting and proliferating cells inside the basement membrane, and spindle- and star-shaped cells proliferating in the outer area of the basement membrane. The characteristics of these myoepithelial cells were confirmed by immunohistochemistry using antibodies raised against keratin, cytokeratin 19, alpha-smooth muscle actin, and vimentin. In simple adenoma, a small number of resting myoepithelial cells was immunopositive for BMP-6. In complex adenomas and benign mixed tumors, all types of myoepithelial cells, depending in some cases on their specific location within the tumor, were immunopositive for BMP-6, but almost all of the tubular epithelial cells were immunonegative. Foci consisting of a proliferation of BMP-6-positive star- and spindle-shaped cells had mucinous stroma with marked hyaline and chondroid changes. In contrast, the foci with BMP-6-negative spindle- and star-shaped cells tended to have mucinous stroma without chondroid change. Several types of mesenchymal cells including chondrocytes, osteoblasts, and fibroblastlike cells in the mixed tumors, showed an intense immunopositive reaction for the BMP-6 antibody, and were located close to the ectopic cartilage and bone matrix. No significant immunoreactivity for BMP-6 was observed in most of the malignant mammary tumors; only one malignant mixed tumor was examined. All of these findings indicate that BMP-6 expression in myoepithelial cells may increase in complex adenomas and benign mixed tumors in canine mammary glands, and that BMP-6 expression is most intense in the vicinity of chondroid matrix in these tumors.  相似文献   

5.
Bone morphogenetic proteins (BMPs) are multi-functional growth factors belonging to the transforming growth factor beta superfamily, especially BMP-2, induce bone formation in vivo, and clinical application in repair of bone fractures and defects is expected. However, appropriate systems to delivery BMPs for practical use need to be developed with the objective to heal cartilage and bone-related diseases in medical, dental and veterinary practice. Thus, the aim of this article was to present an overview of the principals carriers used to delivery BMPs and alternative delivery systems for these proteins.  相似文献   

6.
Bone morphogenetic proteins (BMPs) play important roles in controlling fertility and ovulation rate. There is however, little information on the BMP system in the ovary of a large polyovular species. The aims of the present study were to investigate BMP-2 and -6 protein expression in the porcine ovary, their effects on granulosa cells in culture and their mechanism of action. Cells and oocytes were recovered from healthy antral follicles 2–6 mm in diameter. When assessed by Western blotting, oocytes and follicular fluid contained BMP-2 and -6. In addition, BMP-2 and -6 were observed in granulosa cells and BMP-2 was also found in theca cells. Granulosa cells were cultured in a serum-free system for 144 h in the presence of increasing doses (0, 3, 30 and 100 ng/ml) of BMP-2 or BMP-6. Both BMPs suppressed progesterone production in a dose-dependent manner after 48 h (P < 0.001) and 144 h (P < 0.05). Only BMP-6 stimulated cell proliferation at 100 ng/ml (P < 0.05). Investigation into the mechanism of action found that BMP-2 and -6 decreased cyclic adenosine monophosphate (cAMP) production (P < 0.01), expression of 3β-hydroxysteroid dehydrogenase (3β-HSD) protein (P < 0.001) and steroidogenic acute regulatory protein (StAR) (BMP-6 only; P < 0.05). This supports the hypothesis that BMP-2 and -6 act as luteinization inhibitors. In conclusion, these findings provide evidence for the presence of a complex signalling mechanism in the porcine ovary and suggest that both BMP-2 and -6 may act in a paracrine manner to control granulosa cell function in this large polyovulatory species.  相似文献   

7.
根据GenBank上绵羊的BMP-2基因序列设计特异性引物,以辽宁绒山羊基因组DNA为模板,利用聚合酶链式反应,成功克隆了常年长绒型和季节长绒型辽宁绒山羊BMP-2部分基因片段,丰富了绒山羊BMP-2基因序列。经与绵羊、牛、鼠、猪和人的BMP-2基因进行的比对结果表明,季节与常年长绒型辽宁绒山羊的BMP-2基因同源片段的同源性达到99．7％,二者与绵羊同源性为98．2％和98．4％;与牛同源性为98．2％和97．9％;与鼠同源性为86．3％和86％;与人同源性为88．1％和88．1％。结果表明,辽宁绒山羊BMP-2基因部分核苷酸序列与其他哺乳动物同源性很高,与绵羊、牛的同源性高达97％以上,这与它们的种属关系相近一致。与人、鼠的同源性也在86％以上,说明BMP-2基因在不同物种之间具有较高的保守性。  相似文献   

8.
骨形态发生蛋白-2(BMP-2)能够促进成骨细胞分化和骨组织的再生。将制备的羟基磷灰石/丝素蛋白(HA/SF)复合支架在50μg/mL BMP-2溶液中浸渍4 h后,获得了载入BMP-2的HA/SF复合支架。体外检测在原核表达系统中表达、纯化的BMP-2有促进细胞增殖的生物活性;BMP-2从HA/SF复合支架中的释放可持续9 d,并保持其生物活性,其中BMP-2在第1天的释放率即达到了43%;细胞实验结果显示,与空白HA/SF复合支架相比,载入BMP-2的HA/SF复合支架可以促进人骨肉瘤细胞(MG-63)的增殖与分化;RT-PCR检测BMP-2的加入使细胞内骨钙素基因mRNA转录水平明显提高,即骨钙素基因的表达增强。研究结果提示:HA/SF复合支架可吸附BMP-2并使其缓慢释放,从而促进细胞的增殖与分化,具有良好的细胞相容性,是一种较理想的骨组织缺损修复材料。  相似文献   

9.
Growth differentiation factor-9 (GDF-9) and bone morphogenetic proteins (BMPs), comprise the largest subgroups of ligands in the TGF-β superfamily, and have been shown to be involved in follicle development in mammals. However, whether these factors are involved in folliculogenesis in pigs is still unknown. The present study was performed to determine the relationships between early folliculogenesis and the expression of GDF-9 and BMP (BMP-4, -5 and -6) mRNAs in neonatal pigs. Ovaries were removed at 5, 16, 28 and 39 days after birth to examine the follicular population (the right ovary of each animal) and to detect mRNA expression (the left ovary of each animal). Primordial follicles accounted for >80% of the ovarian follicles from 5 days until 39 days after birth. A marked increase in primary follicles and the appearance of secondary follicles were observed in the ovaries at 28 days after birth. BMP-4, -5, and -6 and GDF-9 mRNAs were expressed by ovaries at 5-, 16-, 28- and 39-day-old pigs. The peak expression of BMP-4, -5, and -6 and GDF-9 mRNAs was observed in the ovaries at 5, 39, 28 and 16 days, respectively, after birth. These data demonstrate that folliculogenesis in piglets might be controlled by the interaction with these factors. We conclude that BMPs and GDF-9 may have distinct functions in several stages of follicle development in neonatal pig ovaries.  相似文献   

10.
To compare the roles of chondromodulin-I (ChM-I) and bone morphogenetic protein-6 (BMP-6) in ectopic mesenchymal tissue formation in canine mammary gland tumors, 33 tumors and 2 normal mammary glands were examined. Immunohistochemical analysis revealed co-expression of ChM-I and BMP-6 in canine mammary tumors. In mixed tumors, newly formed woven bone with ossified cartilage matrix was observed in 4/9 cases. The osteoblasts lining the woven bone showed moderate immunoreactivity to ChM-I and BMP-6. Almost all chondrocytes and proliferative myoepithelial cells within the basement membrane showed intense immunoreactivity to both, and the myoepithelial cells adjacent to the mature cartilage showed the most intense immunoreactivity. The immunoreactivity to ChM-I and BMP-6 of the interstitial myoepithelial cells in the myxomatous stroma varied in each focus of mixed tumors. Similar findings were found in complex adenomas. In simple adenomas, hyperplasic myoepithelial cells within the basement membrane showed moderate immunoreactivity to both markers. Western blot analysis detected a 25 kDa band of ChM-I in fresh tissue samples from three mixed tumors. Our results support the hypothesis that proliferating myoepithelial cells with ChM-I and BMP-6 expression play important roles in mesenchymal metaplasia in canine mammary tumors.  相似文献   

11.
Delivery of growth factors using gene therapy to enhance bone healing   总被引：7，自引：0，他引：7  
OBJECTIVE: To review the delivery of growth factors using gene therapy for enhancing long-bone fracture healing. STUDY DESIGN: Literature review. METHODS: MEDLINE and CAB Abstracts literature search (1980-2004). RESULTS: Non-union and infected non-union are relatively common complications of long-bone fractures in human and veterinary patients. Growth factors are cytokines that regulate many cell functions important in fracture healing. Exogenous growth factors can be delivered to the fracture site as recombinant proteins or using gene therapy. Recombinant human bone morphogenetic protein-2 and -7 (rhBMP-2 and -7), in particular, enhance fracture healing in numerous experimental and clinical studies. Some limitations with use of recombinant proteins may be overcome by use of gene therapy. Gene therapy involves delivery of the growth factor gene to cells at the fracture site using a viral or non-viral vector. The gene is then expressed (protein synthesis) by cells at the fracture site. Delivery of the BMP gene to the fracture site using gene therapy has been evaluated in laboratory animal models of non-union, with favorable results and without complications. CONCLUSION: Delivery of growth factors, particularly members of BMP family, to the fracture site using gene therapy may be a method to enhance fracture healing. Use of this technology may improve the prognosis for patients with long-bone fractures. CLINICAL RELEVANCE: Clinical application of gene therapy could improve the prognosis for human and veterinary patients with long-bone fractures, but has not been evaluated clinically.  相似文献   

12.
Embryonic stem (ES) cells can differentiate spontaneously into various lineages in vitro. However, spontaneous commitment of ES cells to the adipocyte lineage is rare. In the present study, bone morphogenic protein-4 (BMP-4) is described as a factor inducing adipocyte differentiation from ES cells at a high rate. For this reason, ES-cell-derived embryoid bodies (EBs) in suspension cultures were exposed to different doses of BMP-4 for 5 days before they were plated onto gelatin-coated tissue culture plates. Moreover, the effect of serum-containing and serum-free media in three different combinations was assessed. Plated EBs, stained with Sudan Black and processed for transmission and scanning electron microscopy, were observed daily for adipocyte formation. Treatment with BMP-4 resulted in the appearance of adipocyte clusters in EBs' outgrowth, depending on the doses applied. Early in differentiation, many small fat droplets were observed in adipocytes, while later on they coalesced and formed a few large fat droplets. Adipocyte clusters had a fibrillar and vascular stroma, and each adipocyte was surrounded with a reticular external lamina. Furthermore, the appearance and development of adipocytes and their changes following 2-3 weeks of starvation mimicked live adipose tissue. In fact, understanding the biological activity of growth and differentiation factors is needed to regulate and direct stem cell differentiation to specific cell types in vitro.  相似文献   

13.
为探讨人胎盘组织在造血中的作用以及研究造血和神经标志物在胎盘中的表达和在胚胎发育中的相关性，用免疫组织化学法对人胎盘组织和体外培养的胎盘组织中的贴壁细胞进行染色，观察其造血因子和神经标志物的表达。结果发现人7月龄胎盘组织血管内血细胞表达多种造血细胞因子，如SCF、VEGF、BMP-4和FGF-1和KDR，血管内皮细胞上也有表达；胎盘组织同时表达造血干细胞标记CD34、CD133和神经细胞标记物Nestin和MAP2等。而足月龄胎盘CD34、CD133、KDR和造血相关因子SCF、VEGF、BMP-4、FGF-1等弱表达，不表达Nestin和MAP2。两组胎盘切片都不表达GFAP和MBP。胎盘贴壁细胞（hPDACs）碱性磷酸酶、波形蛋白、CD133、Nestin和MAP2染色呈阳性，CD34、GFAP和MBP阴性表达。人胎盘组织和胎盘贴壁细胞表达多种造血相关因子和神经细胞标志物，提示胎盘具有造血功能，造血形成和神经发生之间可能存在基因表达叠加现象。  相似文献   

14.
骨形态发生蛋白-6(BMP-6)是骨形态发生蛋白(BMPs)家族的成员之一,最初研究是发现它具有诱导软骨内骨化、骨折愈合和异位骨形成的活性,但随着研究的逐步深入发现它在动物体内具有非常广泛的作用。本文就它在哺乳动物生殖中的相关研究做一简要总结,初步阐述了BMP-6在哺乳动物与生殖相关的器官中不同细胞类型内的表达格局、信号传递过程及其调控机制、以及BMP-6在调节哺乳动物生殖过程中的作用,并提出一些有待研究的问题。  相似文献   

15.
OBJECTIVE: To determine whether sustained release of transforming growth factor (TGF)-beta1 from a gelatin hydrogel would enhance bone regeneration in critical-sized long-bone defects and overcome inhibitory effects of preoperative irradiation. ANIMALS: 24 adult New Zealand White rabbits. PROCEDURE: Rabbits were allocated to 2 groups. Twelve rabbits received localized megavoltage radiation to the right ulna by use of a cobalt 60 teletherapy unit, and 12 rabbits received no irradiation. Then, a 1.5-cm defect was aseptically created in the right ulna of each rabbit. Gelatin hydrogel that contained 5 microg of adsorbed recombinant-human (rh)TGF-beta1 was placed in the defect of 12 rabbits (6 irradiated and 6 nonirradiated), and the other 12 rabbits received hydrogel without rhTGF-beta1. Rabbits were euthanatized 10 weeks after surgery. New bone formation within the defect was analyzed by use of nondecalcified histomorphometric methods. A 1-way ANOVA was used to compare differences among groups. RESULTS: New bone formation within the defect was significantly greater in TGF-beta1-treated rabbits than in rabbits treated with hydrogel carrier alone. Local delivery of rhTGF-beta1 via a hydrogel carrier in irradiated defects resulted in amounts of bone formation similar to those for nonirradiated defects treated by use of rhTGF-beta1. CONCLUSIONS AND CLINICAL RELEVANCE: Local delivery of TGF-beta1 by use of a hydrogel carrier appears to have therapeutic potential for enhancing bone formation in animals after radiation treatments. IMPACT FOR HUMAN MEDICINE: This technique may be of value for treating human patients at risk for delayed bone healing because of prior radiation therapy.  相似文献   

16.
Bone morphogenetic proteins (BMPs) are emerging as a family of proteins crucial in the regulation of fertility and ovulation rate. We have shown that porcine theca cells express BMP receptors, however, there is a paucity of information regarding the effect(s) of BMPs on theca cell function. The purpose of this study was to investigate the effects of BMP-2 and -6 on theca cells cultured under serum-free conditions in terms of steroidogenesis, cAMP release and proliferation. The study was further extended to determine whether BMP responses in theca cells are affected by the addition of granulosa cells to the culture system. Both BMPs suppressed progesterone and androstenedione synthesis by theca cells (P < 0.05) after 144 h in culture. Oestradiol synthesis was suppressed (P < 0.05) by BMP-2, but not BMP-6, and theca cell proliferation was stimulated (P < 0.05) by BMP-6, but not BMP-2, after 144 h in culture. Both BMP-2 and -6 inhibited cAMP release (P < 0.05) by theca cells. Furthermore, progesterone and androstenedione synthesis by co-cultured theca and granulosa cells were suppressed (P < 0.05) whereas cell proliferation was stimulated (P < 0.05). These results provide strong evidence for a functional BMP system in the porcine ovary and that theca cells are responsive to BMPs in terms of steroidogenesis and proliferation. BMP-2 and -6 may have a role as luteinisation inhibitors in this polyovular species.  相似文献   

17.
This study evaluated the therapeutic effects of a gelatin-β-TCP sponge (sponge) incorporating BMP-2 (BMP-2/sponge) on bone regeneration in equines. Six bone defects were created in third metacarpals of five thoroughbred horses, and a total of six treatments were applied in a randomized manner. The treatments were BMP-2/sponge, BMP-2/gelatin hydrogel sheet (sheet), free BMP-2, bFGF/sheet, plain sponge, and plain sheet. The defects were monitored for 16 weeks by radiography and then examined by histological analysis. Radiographic evaluation scores of bone regeneration revealed significantly greater bone regeneration of defects treated with BMP-2/sponge than defects treated with plain sponge or BMP-2 sheet (P<0.05). In histological analysis, compact bone was observed over a wide area in the BMP-2/sponge treatment. We concluded that the treatment with BMP-2/sponge accelerated bone regeneration in the equines of this study.  相似文献   

18.
Bisphosphonate use has increased in veterinary medicine over the last decade. During this time, bisphosphonate related osteonecrosis of the jaws (BRONJ) in human patients has been identified. Only recently was a dog model for BRONJ developed for human oral surgery and medicine. Veterinary patients treated with bisphosphonates may be at an increased risk for BRONJ There has been little, to no, investigation of potential long term side-effects of bisphosphonate use in veterinary patients; potential sequelae are unknown. The history of bisphosphonates, their use, and BRONJ in veterinary patients are discussed.  相似文献   

19.
The in vitro generation of dendritic cells (DCs) from either blood or bone marrow has been accomplished for humans and a number of other species. This ability has facilitated the opportunity to test the efficacy of DC vaccines in various tumor models. The cottontail rabbit papillomavirus (CRPV) model is the most clinically relevant animal model for human papillomavirus (HPV)-associated carcinogenesis. The CRPV model has been used to test various preventative and therapeutic vaccination strategies, and the availability of rabbit DCs would further expand its utility. However, to date, rabbit DCs have not been phenotypically and/or functionally characterized. Here we show that DCs can be generated in vitro from rabbit bone marrow mononuclear cells (BMMCs) cultured in the presence of the human cytokines GM-CSF and IL-4 and matured with lipopolysaccharide (LPS). These cells show upregulation of MHC class II and CD86, as well as downregulation of CD14, do not have non-specific esterase activity, are able to perform receptor-mediated endocytosis, and are potent stimulators of allogeneic T cell proliferation in mixed lymphocyte reactions. The ability to generate rabbit DCs makes it possible to test the efficacy of DC vaccination in the prevention and treatment of CRPV-induced lesions, which may provide useful preclinical data regarding the use of DC vaccines for HPV-associated lesions, including cervical cancer.  相似文献   

20.
Nosocomial infections and antimicrobial resistance are topics that have been intensely studied in human medicine because of their significant impact on human health. In recent years, concerns have been raised that the use of antibiotics in veterinary medicine, animal husbandry, and agriculture may be contributing to the development of resistance in common bacterial species affecting human beings. Although there is inadequate proof at this time that the resistance is transmitted from animals to people, if antibiotics continue to be used indiscriminately in veterinary medicine, veterinarians may find themselves facing regulations restricting the use of some antibiotics. Nosocomial infections have been reported in veterinary medicine and are likely to increase in prevalence with the increase in intensive care practices in many hospitals. Prolonged hospitalization and the use of invasive devices and procedures increase the risk of nosocomial disease. As in human medicine, organisms isolated in the nosocomial infections reported in veterinary patients have an increasingly broad spectrum of antimicrobial resistance. Despite these findings, the use of empiric and prophylactic antibiotic therapy is still widespread in veterinary medicine. Nosocomial infections and antimicrobial resistance may have a serious impact on the future of [table: see text] veterinary medicine, because the cost and ability to treat our patients may be affected by the loss of access to or effectiveness of antimicrobial drugs. Despite the millions of dollars spent on research to reduce the incidence of nosocomial infections in human patients, the strategies that have consistently proven successful are simple and inexpensive to implement. The most important factor in preventing nosocomial infections is improving the hygiene practices of health care providers. Hand-washing or the use of disposable gloves can dramatically reduce the transmission of bacteria between patients. Aseptic technique should be used in the placement and management of all invasive devices. All staff members should be educated on the risks and symptoms associated with nosocomial infections so that cases can be detected early and treated appropriately. We in the veterinary profession have the opportunity to learn from the experiences of the human medical profession and can take steps to prevent the escalation of nosocomial infections and their impact on our profession.  相似文献   

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