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Isabelle Brigaud, Rémy Agniel, Johanne Leroy Dudal, Sabrina Kellouche, Arnaud Ponche, Tahar Bouceba, Natalia Mihailescu, Mihai Sopronyi, Eric Viguier, Carmen Ristoscu, Felix Sima, Ion N Mihailescu, Ana Claudia O Carreira, Mari Cleide Sogayar, Olivier Gallet, Karine Anselme
Design of new osteoinductive biomaterials to reproduce an optimized physiological environment capable of recruiting stem cells and instructing their fate towards the osteoblastic lineage has become a priority in orthopedic surgery. This work aims at evaluating the bioactivity of BMP combined with human plasma fibronectin (FN/BMP) delivered in solution or coated onto titanium-hydroxyapatite (TiHA) surfaces. Herein, we focus on the comparison of in vitro osteogenic efficacy in mouse C2C12 pre-osteoblasts of three BMP members, namely: BMP-2, BMP-6 and BMP-7...
April 18, 2017: Acta Biomaterialia
Xiaoyuan Xu, He Jiang, Xingnuan Li, Ping Wu, Jianyun Liu, Tao Wang, Xiaoou Zhou, Jianjun Xiong, Weidong Li
The present study aimed to screen several differentially expressed genes (DEGs) and differentially expressed microRNAs (miRNAs) for two types of mesenchymal stem cell (MSC) differentiation. Bone morphogenetic protein 6 (BMP‑6) and dexamethasone were used to induce MSCs towards osteoblastic differentiation or adipocytic differentiation. The t‑test in the Bioconductor bioinformatics software tool was used to screen DEGs and differentially expressed miRNAs in the two samples. Subsequent gene ontology (GO) and pathway analyses on the DEGs were performed using the GO and Kyoto Encyclopedia of Genes and Genomes databases, respectively; potential target genes for the screened miRNAs were predicted using the TargetScan database...
April 2017: Molecular Medicine Reports
Gustavo A Rico-Llanos, Jose Becerra, Rick Visser
Bone morphogenetic protein-2 (BMP-2) is widely used in orthopedic surgery and bone tissue engineering because of its strong osteogenic activity. However, BMP-2 treatments have several drawbacks and many groups are actively exploring alternatives. Since BMP-6 has been demonstrated to be more osteoinductive, its use, either alone or together with other growth factors, might be an interesting option. In this work, we have compared the effect of BMP-2, BMP-6, or insulin-like growth factor-1 (IGF-1), either alone or in combination...
March 3, 2017: Journal of Biomedical Materials Research. Part A
Qi Tang, Li-Li Chen, Fen Wei, Wei-Lian Sun, Li-Hong Lei, Pei-Hui Ding, Jing-Yi Tan, Xiao-Tao Chen, Yan-Min Wu
BACKGROUND: 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), one of the major metabolites from prostaglandin D2 in arachidonic acid metabolic pathway, has potential anti-inflammatory properties. The objective of this study was to explore the effects of 15d-PGJ2-loaded poly(D,L-lactide-co-glycolide) nanocapsules (15d-PGJ2-NC) on inflammatory responses and bone regeneration in local bone defect. METHODS: The study was conducted on 96 Wistar rats from June 2014 to March 2016...
February 5, 2017: Chinese Medical Journal
Eun-Jeong Kwon, Moon-Moo Kim
Agmatine contained in soybean is also found in Manaca, an anti-aging plant, inhabited in Amazon and induces vasodilation by the promotion of NO synthesis in blood vessel. However, the research of agmatine on melanin synthesis related to hair greying is lacking. The aim of this study was to investigate the melanogenic effect of agmatine via regulation of MITF signaling pathway in B16F1 cells. It was determined whether agmatine regulates melanin synthesis at cellular level in addition to the effect of agmatine on mushroom tyrosinase in vitro in the presence of different concentrations of agmatine...
January 2017: Environmental Toxicology and Pharmacology
H Iijima, A Ito, M Nagai, J Tajino, S Yamaguchi, W Kiyan, A Nakahata, J Zhang, T Wang, T Aoyama, K Nishitani, H Kuroki
OBJECTIVE: To evaluate the dose-response relationship of exercise loading in the cartilage-subchondral bone (SB) unit in surgically-induced post-traumatic osteoarthritis (PTOA) of the knee. DESIGN: Destabilized medial meniscus (DMM) surgery was performed on the right knee of 12-week-old male Wistar rats, and sham surgery was performed on the contralateral knee. Four weeks after the surgery, the animals were subjected to moderate (12 m/min) or intense (21 m/min) treadmill exercises for 30 min/day, 5 days/week for 4 weeks...
December 10, 2016: Osteoarthritis and Cartilage
Jose Rafael Villafan-Bernal, Lorenzo Franco-De La Torre, Ana Soledad Sandoval-Rodriguez, Juan Armendariz-Borunda, Juan Luis Alcala-Zermeno, Jose Alfonso Cruz-Ramos, Gabriela Lopez-Armas, Blanca Estela Ramirez-Bastidas, Gracia Viviana González-Enríquez, Emerson Armando Collazo-Guzman, Raigam Jafet Martinez-Portilla, Sergio Sánchez-Enríquez
Bone fractures are a worldwide public health concern. Therefore, improving understanding of the bone healing process at a molecular level, which could lead to the discovery of potential therapeutic targets, is important. In the present study, a model of open tibial fractures with hematoma disruption, periosteal rupture and internal fixation in 6-month-old male Wistar rats was established, in order to identify expression patterns of key genes and their protein products throughout the bone healing process. A tibial shaft fracture was produced using the three-point bending technique, the hematoma was drained through a 4-mm incision on the medial aspect of the tibia and the fracture stabilized by inserting a needle into the medullary canal...
November 2016: Experimental and Therapeutic Medicine
Susanna Canali, Kimberly B Zumbrennen-Bullough, Amanda B Core, Chia-Yu Wang, Manfred Nairz, Richard Bouley, Filip K Swirski, Jodie L Babitt
Bone morphogenetic protein 6 (BMP6) signaling in hepatocytes is a central transcriptional regulator of the iron hormone hepcidin that controls systemic iron balance. How iron levels are sensed to regulate hepcidin production is not known, but local induction of liver BMP6 expression by iron is proposed to have a critical role. To identify the cellular source of BMP6 responsible for hepcidin and iron homeostasis regulation, we generated mice with tissue-specific ablation of Bmp6 in different liver cell populations and evaluated their iron phenotype...
January 26, 2017: Blood
Yahya Açil, Amir Alexander Ghoniem, Aydin Gülses, Tobias Kisch, Felix Stang, Jörg Wiltfang, Matthias Gierloff
Recent studies indicated a lower osteogenic differentiation potential of adipose tissue-derived stromal cells (ASCs) compared to bone marrow derived mesenchymal stromal cells. The aim of this study was to evaluate the effects of potent combinations of highly osteogenic bone morphogenetic proteins (BMPs) in order to enhance the osteogenic differentiation potential of ASCs. Human ASCs were cultured for 10 days in the presence of osteogenic medium consisting of dexamethasone, ß-glycerophosphate and ascorbat-2-phosphate (OM) supplemented with BMP-2, BMP-6, BMP-9+IGF-2 and BMP-2,-6,-9 (day 1+2: 50 ng/ml, days 3-6: 100 ng/ml, days 7-10: 200 ng/ml)...
January 2017: Journal of Cranio-maxillo-facial Surgery
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...
December 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...
January 5, 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
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