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Alan Cheng, Amber Renee Gustafson, Christine Elizabeth Schaner Tooley, Mei Zhang
Current cartilage repair therapies focus on the delivery of chondrocytes differentiated from mesenchymal stem cells, and thus understanding the factors that promote chondrogenesis may lead to improved therapies. Several bone morphogenetic proteins (BMPs) have been implicated in chondrogenic differentiation and/or chondrocyte function. Although the signaling pathways downstream of BMPs have been studied in other systems, their role in chondrogenesis is less well characterized. Here, we investigated the effects of BMP-9 in chondroprogenitor cells...
April 4, 2016: Differentiation; Research in Biological Diversity
Senem Aykul, Erik Martinez-Hackert
Cerberus is a key regulator of vertebrate embryogenesis. Its biological function has been studied extensively in frog and mouse embryos. Its ability to bind and antagonize the transforming growth factor-β (TGF-β) family ligand Nodal is well established. Strikingly, the molecular function of Cerberus remains poorly understood. The underlying reason is that Cerberus is a complex, multifunctional protein: It binds and inhibits multiple TGF-β family ligands, it may bind and inhibit some Wnt family members, and two different forms with distinct activities have been described...
February 13, 2016: Journal of Molecular Biology
J K Chambers, Y Yoshino, R Fujiwara, R Nishimura, H Nakayama, K Uchida
An 11-year-old female Chihuahua exhibited respiratory distress and a computed tomography scan showed a large mass in the anterior thoracic cavity. During surgery, it was found that the mass was strongly adherent to surrounding tissue. A histopathological examination of a biopsy sample from the mass revealed proliferation of atypical epithelial cells and cartilage formation admixed with mature lymphocytes. Immunohistochemically, the tumour cells, as well as the normal canine thymic epithelial cells, were positive for pan-cytokeratin (CK), CK5/6, CK19, p63 and bone morphogenetic protein (BMP) 6...
January 2016: Journal of Comparative Pathology
Kishio Toma, Fumio Otsuka, Kohei Oguni, Tomohiro Terasaka, Motoshi Komatsubara, Naoko Tsukamoto-Yamauchi, Kenichi Inagaki, Hirofumi Makino
The effects of somatostatin analogs and roles of BMP-6 in the regulation of luteinizing hormone (LH) secretion were investigated using mouse gonadotrope LβT2 cells. LH mRNA expression and LH secretion induced by GnRH were suppressed by treatments with somatostatin analogs, including octreotide and pasireotide, in LβT2 cells. Of note, the inhibitory effects of somatostatin analogs on LH secretion were enhanced by the action of BMP-6. BMP-6 increased the expression levels of somatostatin receptor (SSTR)5, suggesting that BMP-6 upregulates SSTR activity that leads to reduction of GnRH-induced LH secretion...
February 2016: Peptides
Fen Hu, Yunfeng Zhang, Mi Li, Lina Zhao, Jing Chen, Shuang Yang, Xiujun Zhang
Bone morphogenetic protein-6 (BMP-6) is a multifunctional molecule with distinct abilities in embryogenesis and organogenesis. In the present study, our results showed that the rate of BMP-6-negative expression was 30.56% in breast cancer tissues, but was 9.58% in normal tissues by immunohistochemical staining. This implied that BMP-6 expression is absent in breast cancer tissues and may suppress breast cancer metastasis. In addition, stable overexpression of BMP-6 in MDA-MB‑231 cells was established to analyze the metastatic ability...
March 2016: Oncology Reports
J Bolander, W Ji, L Geris, V Bloemen, Y C Chai, J Schrooten, F P Luyten
When combining osteogenic progenitor cells such as human periosteum derived cells (hPDCs) with osteoconductive biomaterials like calcium phosphate (CaP)-scaffolds, in vivo bone formation can be achieved. This process is dependent on the early activation of Bone morphogenetic protein (BMP)-signalling. However, the bone forming process is slow and routinely only a limited amount of bone and bone marrow is formed. Therefore, we hypothesised that a robust clinically relevant outcome could be achieved by adding more physiological levels of potent BMP-ligands to these cell- and CaP-based constructs...
2016: European Cells & Materials
Chen-Shuang Li, Xinli Zhang, Bruno Péault, Jie Jiang, Kang Ting, Chia Soo, Yan-Heng Zhou
Osteoarthritis is the leading cause of disability in the US. Consequently, there is a pressing need for restoring the structural and functional properties of diseased articular cartilage. Yet the search for the right combination of proper target cells and growth factors for cartilage regeneration remains challenging. In this study, we first tested the intrinsic chondrogenic differentiation ability of human perivascular stem cells (hPSCs), a novel source of mesenchymal stem cells (MSCs) isolated by fluorescence-activated cell sorting (FACS) from human adipose tissue...
February 2016: Tissue Engineering. Part A
T Tolga Demirtaş, Eda Göz, Ayşe Karakeçili, Menemşe Gümüşderelioğlu
Natural microenvironment during bone tissue regeneration involves integration of multiple biological growth factors which regulate mitogenic activities and differentiation to induce bone repair. Among them platelet derived growth factor (PDGF-BB) and bone morphogenic protein-6 (BMP-6) are known to play a prominent role. The aim of this study was to investigate the benefits of combined delivery of PDGF-BB and BMP-6 on proliferation and osteoblastic differentiation of MC3T3-E1 preosteoblastic cells. PDGF-BB and BMP-6 were loaded in gelatin and poly (3-hydroxybutyric acid-co-3-hydroxyvaleric acid) particles, respectively...
January 2016: Journal of Materials Science. Materials in Medicine
V R Araújo, G M Silva, A B G Duarte, D M Magalhães-Padilha, A P Almeida, F O Lunardi, M K B Serafim, A A A Moura, C C Campello, A P R Rodrigues, J R Figueiredo
BMP-6 has been found to be important to ovarian cells and oocyte, as well as to uterus. Thus, this study investigated the effect of bone morphogenetic protein (BMP-6) and recombinant follicle-stimulating hormone (rFSH) alone or in combination on the in vitro culture (IVC) of isolated caprine secondary follicles (Experiment 1) and the mRNA levels for BMP receptors/Smad signalling pathway (BMPR1A, BMPR2, SMAD1, SMAD4, SMAD5, SMAD6, SMAD7 and SMAD8) in vivo and in vitro using BMP-6 (Experiment 2). Secondary follicles were cultured in αMEM(+) alone (control medium) or supplemented with BMP-6 at 1 or 10 ng/ml and rFSH alone or the combination of both BMP-6 concentrations and rFSH...
February 2016: Reproduction in Domestic Animals, Zuchthygiene
Shun-Fu Chang, Rong-Ze Hsieh, Kuo-Chin Huang, Cheng Allen Chang, Fang-Yao Chiu, Hsing-Chun Kuo, Cheng-Nan Chen, Yu-Ping Su
Bone morphogenetic proteins (BMPs) play positive roles in cartilage development, but they can barely be detected in healthy articular cartilage. However, recent evidence has indicated that BMPs could be detected in osteoarthritic and damaged cartilage and their precise roles have not been well defined. Extremely high amounts of leptin have been reported in obese individuals, which can be associated with osteoarthritis (OA) development. The aim of this study was to investigate whether BMPs could be induced in human primary chondrocytes during leptin-stimulated OA development and the underlying mechanism...
2015: PloS One
Anusuya Das, Brian A Fishero, J Jared Christophel, Ching-Ju Li, Nikita Kohli, Yong Lin, Abhijit S Dighe, Quanjun Cui
We have previously shown that the combined delivery of mesenchymal stem cells (MSCs), vascular endothelial growth factor (VEGF) and bone morphogenetic protein 6 (BMP-6) induces significantly more bone formation than that induced by the delivery of any single factor or a combination of any two factors. We now determine whether the exogenous addition of VEGF and BMP-6 is sufficient for bone healing when MSCs are not provided. Poly(lactic-co-glycolic acid) (PLAGA) microsphere-based three-dimensional scaffolds (P) were fabricated by thermal sintering of PLAGA microspheres...
April 2016: Cell and Tissue Research
I M Polat, E Alçiğir, M Pekcan, S A Vural, E Özenç, H E Canatan, Ş Küplülü, G E Dal, M O Yazlik, C Baklaci, M R Vural
The process of transformation of growing bovine follicles into cysts is still a mystery. Local expression of proteins or factors, including transforming growth factor β, growth factors, and transcription factors, plays a central role in mammals. Therefore, in abattoir-derived cystic ovarian follicles and follicular fluid, the role of some transforming growth factor β superfamily proteins, insulinlike growth factor-1 (IGF-1) and GATA-4 and GATA-6, were investigated. The relationship between intrafollicular lipopolysaccharide (LPS) and etiopathogenesis of ovarian cysts was also assessed...
October 1, 2015: Theriogenology
Lili Chen, Fen Wei, Weilian Sun, Peihui Ding, Xiaotao Chen, Yanmin Wu
OBJECTIVE: To investigate the effect of local delivery of delta12-prostaglandinJ2-loaded poly (lactic-co-glycolic acid) (Δ(12)-PGJ2-NC) on growth factors expression and bone formation. METHODS: Δ(12)-PGJ2-NC was prepared by the emulsion solvent diffusion method. The physical and chemical properties of the nanoparticles were evaluated by particle size analysis, transmission electron microscopy, drug-loading ratio and the in vitro release study. Then standardized transcortical defect (5...
March 2015: Zhonghua Kou Qiang Yi Xue za Zhi, Zhonghua Kouqiang Yixue Zazhi, Chinese Journal of Stomatology
Oddrun Elise Olsen, Karin Fahl Wader, Hanne Hella, Anne Kærsgaard Mylin, Ingemar Turesson, Ingerid Nesthus, Anders Waage, Anders Sundan, Toril Holien
BACKGROUND: Activins are members of the TGF-β family of ligands that have multiple biological functions in embryonic stem cells as well as in differentiated tissue. Serum levels of activin A were found to be elevated in pathological conditions such as cachexia, osteoporosis and cancer. Signaling by activin A through canonical ALK4-ACVR2 receptor complexes activates the transcription factors SMAD2 and SMAD3. Activin A has a strong affinity to type 2 receptors, a feature that they share with some of the bone morphogenetic proteins (BMPs)...
2015: Cell Communication and Signaling: CCS
Xiangzhu Cun, Jing Xie, Shiyu Lin, Na Fu, Shuwen Deng, Qiang Xie, Juan Zhong, Yunfeng Lin
OBJECTIVES: The aim of this study was to investigate gene expressions of growth factors for angiogenesis, in a three-dimensional (3D) gel populated with adipose-derived stromal cells (ASCs) and endothelial cells (ECs) in co-culture. MATERIALS AND METHODS: The 3D gel, mixed with green fluorescent protein (GFP)-positive ASCs and DsRed-Express-positive ECs, 1:1 ratio, was established in vitro. The phenomenon of angiogenesis was observed using confocal microscopy. To detect gene expressions for growth factor proteins in both ASCs and ECs, transwell co-culture was used, and cell lysate samples were collected at 1, 3, 5 and 7 days...
August 2015: Cell Proliferation
Xiyan Wang, Li Su, Xiaoyan Pan, Jian Yao, Zhixin Li, Xuenan Wang, Bangsheng Xu
The aim of this study was to investigate the effect and mechanism of bone morphogenetic protein-6 (BMP-6) on the growth and maturation of mouse follicles in vitro. Preantral follicles isolated from mice were incubated with recombinant human BMP-6 (rhBMP-6) before analysis. BMP-6 expression was detected by immunofluorescence and western blot. Maturation of oocytes was observed microscopically. Estradiol (E2) and progesterone (P4) levels were measured by enzyme-linked immunosorbent assay. Expression of steroidogenesis-related genes was detected by reverse transcription quantitative polymerase chain reaction...
March 4, 2015: Biotechnology, Biotechnological Equipment
Felicia Gomez, Lihua Wang, Haley Abel, Qunyuan Zhang, Michael A Province, Ingrid B Borecki
BACKGROUND: Coronary artery calcification (CAC) is an imaging biomarker of coronary atherosclerosis. In European Americans, genome-wide association studies (GWAS) have identified several regions associated with coronary artery disease. However, few large studies have been conducted in African Americans. The largest meta-analysis of CAC in African Americans failed to identify genome-wide significant variants despite being powered to detect effects comparable to effects identified in European Americans...
2015: BMC Genetics
Wu Yang, Chang Liu
In recent years, there has been a growing emphasis on use of human adipose-derived stem cells (hADSCs) for cartilage tissue engineering owing to their ability to differentiate into chondrocytes, which is mainly induced by growth factors (GFs). In general, GFs for chondrogenic induction come from the transforming growth factor beta (TGF-beta) superfamily. To date, the most commonly used GFs for chondrogenes is TGF-beta1/3. However, the response of hADSCs to GFs may differ significantly from that of human bone marrow stem cells (hBMSCs)...
December 2014: Sheng Wu Yi Xue Gong Cheng Xue za Zhi, Journal of Biomedical Engineering, Shengwu Yixue Gongchengxue Zazhi
Ching-Ju Li, Vedavathi Madhu, Gary Balian, Abhijit S Dighe, Quanjun Cui
Deficiency in vascular endothelial growth factor (VEGF) or bone morphogenetic proteins (BMPs) results in fracture non-unions. Therefore, it is indispensable to comprehend the combined effect of VEGF and BMPs on the osteogenic differentiation of osteoprogenitor mesenchymal stem cells (MSCs) that are either naturally occurring at the fracture repair site or exogenously added to enhance the bone repair. We found that the combination of VEGF and BMP-6 enhanced COL1A2 expression, which correlated with upregulated expression of osterix, Dlx5, and Msx2 in human adipose-derived stem cells (hADSCs)...
November 2015: Journal of Cellular Physiology
Ugo Ripamonti, Thérèse Dix-Peek, Ruqayya Parak, Brenda Milner, Raquel Duarte
To study the expression profile of bone morphogenetic proteins and transforming growth factor-βs (BMPs and TGFβs), coral-derived calcium carbonate-based macroporous bioreactors with limited conversion to hydroxyapatite (7% HA/CC) were pre-loaded with and without 250 μg hTGF-β3 and implanted in the rectus abdominis of 3 non-human primates Papio ursinus euthanized on day 60. To investigate the required dose of hNoggin, a BMPs antagonist that controls the induction of bone formation, 7% HA/CC were pre-loaded with 150 μg hNoggin, with 125 μg hTGF-β3/150 μg hNoggin, with or without 125 μg hTGF-β3 and implanted in the r...
May 2015: Biomaterials
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