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Yanjiang Xing, Shuang Zhao, Qingxia Wei, Shiqiang Gong, Xin Zhao, Fang Zhou, Rafia Ai-Lamki, Daniel Ortmann, Mingxia Du, Roger Pedersen, Guangdong Shang, Shuyi Si, Nicholas W Morrell, Jun Yang
Genetic defects in bone morphogenetic protein type-II receptor (BMPRII) signalling and inflammation contribute to the pathogenesis of pulmonary arterial hypertension (PAH). The receptor is activated by BMP ligands, which also enhance BMPR2 transcription. A small molecule BMP upregulator with selectivity on vascular endothelium would represent a desirable therapeutic intervention for PAH.We assayed compounds identified in the screening of BMP2 upregulators for their ability to increase expression of Inhibitor of DNA binding 1 (Id1), using a dual reporter driven specifically in human embryonic stem cell (hESC)-derived endothelial cells (ECs)...
February 15, 2018: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
Tingfang Sun, Man Liu, Sheng Yao, Yanhui Ji, Lei Shi, Kai Tang, Zekang Xiong, Fan Yang, Kaifang Chen, Xiaodong Guo
Introduction: At present, the treatment of osteoporotic defects poses a great challenge to clinicians, owing to the lower regeneration capacity of the osteoporotic bone as compared with the normal bone. The guided bone regeneration (GBR) technology provides a promising strategy to cure osteoporotic defects using bioactive membranes. The decellularized matrix from the small intestinal submucosa (SIS) has gained popularity for its natural microenvironment, which induces cell response. Materials and methods: In this study, we developed heparinized mineralized SIS loaded with bone morphogenetic protein 2 (BMP2)-related peptide P28 (mSIS/P28) as a novel GBR membrane for guided osteoporotic bone regeneration...
2018: International Journal of Nanomedicine
Binyu Luo, Kang Chen, Qi Feng, Weidong Xiao, Dan Ma, Hua Yang, Chaojun Zhang
The number and function of intestinal intraepithelial lymphocytes (IELs) have been found to be significantly reduced following induction of acute intestinal mucosal damage via intestinal ischemia̸reperfusion (I̸R). However, the mechanism underlying this reduction remains unclear. Therefore, it was hypothesized that the interplay of bone morphogenetic protein (BMP)4 and interleukin (IL)‑7 regulates IEL function and number. Recent studies have demonstrated that the different components of the BMP2̸4 signaling pathway are expressed in intestinal epithelial cells (IECs) via the activation of nuclear factor (NF)‑κB...
February 9, 2018: International Journal of Molecular Medicine
Chijian Zuo, Xiaoying Zhao, Yu Shi, Wen Wu, Ning Zhang, Jiake Xu, Chuandong Wang, Guoli Hu, Xiaoling Zhang
Although the mechanisms of Tumor necrosis factor alpha (TNF-α) on facilitating osteoclast differentiation and bone resorption is well known, the mechanisms behind the suppression of the osteoblast differentiation from mesenchymal stem cells (MSCs) are still poorly understood. In this study, we observed a negative correlation between TNF-α levels and the expression of special AT-rich sequence-binding protein 2 (SATB2), a critical osteoblastogenesis transcription factor, in ovariectomy (OVX)-induced bone loss and IL-1-induced arthritis animal model...
January 12, 2018: Oncotarget
Zhi-Yuan Cheng, Ting Ye, Qiu-Yang Ling, Ting Wu, Gang-Yong Wu, Gang-Jun Zong
Vascular calcification (VC) occurs in patients with chronic kidney disease (CKD) and contributes to cardiovascular dysfunction and mortality. Parathyroid hormone (PTH) is a crucial regulator of VC. High PTH serum levels constitute as a major risk factor for patients with CKD. However, the effect and mechanism of PTH on osteoblastic differentiation in endothelial cells have not been fully elucidated. In the present study, the role of PTH in VC was investigated using an in vitro calcification model. Endothelial cells were stimulated with PTH in the femto- to picomolar range...
February 2018: Experimental and Therapeutic Medicine
Sarah McBride-Gagyi, Zacharie Toth, Daniel Kim, Victoria Ip, Emily Evans, J Tracy Watson, Daemeon Nicolaou
The Masquelet technique depends on pre-development of a foreign-body membrane to support bone regeneration with grafts over three times larger than the traditional maximum. To date, the procedure has always used spacers made of bone cement, which is the polymer polymethyl methacrylate (PMMA), to induce the foreign-body membrane. This study sought to compare (i) morphology, factor expression, and cellularity in membranes formed by PMMA, titanium, and polyvinyl alcohol sponge (PVA) spacers in the Masquelet milieu and (ii) subsequent bone regeneration in the same groups...
February 9, 2018: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
Kang Zhou, Xiuli Ren, Mengen Zhao, Xifan Mei, Peng Zhang, Zhenhua Chen, Xiangdong Zhu
In this article, we proposed a facile protocol to functionalize porous calcium phosphate ceramics (PCPC) using dietary tea polyphenols (TP). TP molecules was attracted and anchored by Ca2+ ions from the surface of CPC. These TP molecules modulated the nucleation and crystallization of calcium phosphate nanorods assemblies on the surface of PCPC. Our results prove that these calcium phosphate nanorods assemblies accompanies functional groups of TP make PCPC/TP effectively promote proliferation and differentiation of bone mesenchymal stem cells (BMSCs)...
February 2018: Regenerative Biomaterials
Ramkumar T Annamalai, Paul A Turner, William F Carson, Benjamin Levi, Steven Kunkel, Jan P Stegemann
Biomaterials-based approaches to harnessing the immune and inflammatory responses to potentiate wound healing hold important promise. Bone fracture healing is characterized by an acute inflammatory phase, followed by a transition to a regenerative and repair phase. In this study, we developed genipin-crosslinked gelatin microspheres designed to be preferentially degraded by inflammatory (M1) macrophages. Highly crosslinked (>90%) microspheres allowed efficient incorporation of bioactive bone morphogenetic protein 2 (BMP2), a potent stimulator of osteogenesis in progenitor cells, via electrostatic interactions...
February 3, 2018: Biomaterials
Hong-Jin Zhao, Christian Klausen, Yan Li, Hua Zhu, Yan-Ling Wang, Peter C K Leung
BMP2 expression is spatiotemporally correlated with embryo implantation and is crucial for endometrial decidualization and fertility in mice. BMP2 has been reported to increase the mesenchymal adhesion molecule N-cadherin and enhance cell invasion in cancer cells; moreover, studies suggest that N-cadherin promotes placental trophoblast invasion. However, whether BMP2 can promote trophoblast cell invasion during placentation remains unknown. The objective of our study was to investigate the effects of BMP2 on human trophoblast cell invasion and the involvement of N-cadherin and SMAD signaling...
February 7, 2018: Cell Death & Disease
Marianna De Colli, Milena Radunovic, Vincenzo L Zizzari, Viviana di Giacomo, Chiara Di Nisio, Adriano Piattelli, José L Calvo Guirado, Barbara Zavan, Amelia Cataldi, Susi Zara
Titanium surface modification is critical for dental implant success. Our aim was to determine surfaces influence on dental pulp stem cells (DPSCs) viability and differentiation. Implants were divided into sandblasted/acid-etched (control) and sandblasted/acid-etched coated with calcium and magnesium ions (CaMg), supplied as composite, (test). Proliferation was evaluated by MTT, differentiation checking osteoblastic gene expression, PGE2 secretion and matrix formation, inflammation by Interleukin 6 (IL-6) detection...
February 8, 2018: Dental Materials Journal
Jennifer L Graef, Elizabeth Rendina-Ruedy, Erica K Crockett, Ping Ouyang, Jarrod B King, Robert H Cichewicz, Edralin A Lucas, Brenda J Smith
Dried plum supplementation has been shown to enhance bone formation while suppressing bone resorption. Evidence from previous studies has demonstrated that these responses can be attributed in part to the fruit's polyphenolic compounds. The purpose of this study was to identify the most bioactive polyphenolic fractions of dried plum with a focus on their osteogenic activity and to investigate their mechanisms of action under normal and inflammatory conditions. Utilizing chromatographic techniques, six fractions of polyphenolic compounds were prepared from a crude extract of dried plum...
September 29, 2017: Journal of Nutritional Biochemistry
Sepanta Hosseinpour, Maryam Rezai Rad, Arash Khojasteh, Homa Zadeh
BACKGROUND: Currently, antibodies are progressively applied in medicine for different purposes from diagnosis to treatments. Over twenty monoclonal antibodies utilized for many therapeutic reasons from therapy of cancers, immune disorders, and osteoporosis to localized bony defects. In addition, therapeutic antibodies represented various findings in bone tissue engineering. OBJECTIVES: The current study aims to systematically review the available literature on antibody assisted bone regeneration in animal models...
February 6, 2018: Current Stem Cell Research & Therapy
Wenyu Yang, Yiting Cao, Zhe Zhang, Fuchong Du, Yanping Shi, Xuemin Li, Qiqing Zhang
It is reported that growth factor (GF) is able to enhance the repair of articular cartilage (AC) defect, however underlying mechanisms of which are not fully elucidated yet. Moreover, the strategy for delivering GF needs to be optimized. The crosstalk between AC and subchondral bone (SB) play important role in the homeostasis and integrity of AC, therefore SB targeted delivery of GF represents one promising way to facilitate the repair of AC defect. In this study, we firstly investigated the effects and mechanism of FGF2 on surrounding SB and cartilage of detect defects in rabbits by using a homogenous collagen-based membranes...
February 1, 2018: Acta Biomaterialia
Yutong Li, Wenji Hu, Guanghong Han, Wenqian Lu, Dongxu Jia, Min Hu, Di Wang
Aucubin, an iridoid glycoside found in several plants, such as Eucommia ulmoide and Rehmannia, has various pharmacological effects. Bone formation is a complex process in which osteoblast differentiation plays an important role. This study aimed to investigate the promotion effects of aucubin on osteoblast differentiation in MG63 cells, a human osteoblast-like cell line. Aucubin not only improved osteoblast differentiation, as shown by enhanced ALP (alkaline phosphatase) concentration and mineralization in cells, but increased the expression of various cytokines, including collagen I, osteocalcin, osteopontin, integrin β1, and Osterix...
February 3, 2018: Chemico-biological Interactions
Shruthy Kuttappan, A Anitha, M G Minsha, Parvathy M Menon, T B Sivanarayanan, Lakshmi Sumitra Vijayachandran, Manitha B Nair
The treatment of critical sized bone defect remains a significant challenge in orthopedics. The objective of the study is to evaluate the effect of the combination of bone morphogenetic protein 2 (BMP2) expressing genetically engineered mesenchymal stem cells (MSCs) [MSCs engineered using a multimam vector, pAceMam1, an emerging gene delivery vector] and an osteoconductive scaffold [silica coated nanohydroxyapatite-gelatin reinforced with fibers] in enhancing bone regeneration in critical sized segmental defects...
April 1, 2018: Materials Science & Engineering. C, Materials for Biological Applications
Hyo-Eun Son, Kyeong-Min Kim, Eun-Jung Kim, Won-Gu Jang
Kisspeptin-10 (KP-10) acts as a tumor metastasis suppressor via its receptor, G-protein-coupled receptor 54 (GPR54). The KP-10-GPR54 system plays an important role in embryonic kidney development. However, its function in osteoblast differentiation is unknown. Osteoblast differentiation is controlled by a range of hormones and cytokines, such as bone morphogenetic protein (BMPs), and multiple transcription factors, such as Runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP), and Distal-less homeobox 5 (Dlx5)...
February 1, 2018: Scientific Reports
Jaakko V I Piesanen, Seppo T Nikkari, Tarja A Kunnas
Bone morphogenetic proteins (BMPs) are important regulators of iron metabolism affecting hepcidin expression. We have previously shown that 2 genetic polymorphisms in different genes (histocompatibility complex class I-like transmembrane protein, hemojuvelin) involved in the regulation of hepcidin expression pathways are associated with hypertension. In this study, we analyzed genetic variation sites in BMP2 (rs235756, rs235768) and BMP4 (rs4901474) to get more evidence linking iron metabolism to hypertension risk in the Finnish population...
December 2017: Medicine (Baltimore)
Endre Soreide, Janet M Denbeigh, Eric A Lewallen, Rebekah M Samsonraj, Lawrence J Berglund, Amel Dudakovic, Simon M Cool, Lars Nordsletten, Sanjeev Kakar, Andre J van Wijnen
Tendon graft healing in bone tunnels for the fixation of intra-articular ligament reconstructions may limit clinical outcome by delaying healing. This study assesses the effects of hydrogel-mediated delivery of bone anabolic growth factors in a validated model of tendon-to-bone tunnel healing. Forty-five Wistar rats were randomly allocated into three groups (BMP2-treated, GSK126-treated, and placebo). All animals underwent a tendon to bone tunnel reconstruction. Healing was evaluated at 4 weeks by biomechanical assessment, micro-computed tomography (bone mineral density, bone volume, cross sectional area of bone tunnels), and traditional histology...
February 1, 2018: Journal of Cellular Biochemistry
Yifan Liu, Yunjie Tu, Ming Zhang, Gaige Ji, Kun Wang, Yanju Shan, Xiaojun Ju, Di Zhang, Jingting Shu, Jianmin Zou
The comb of the male is an important secondary sexual characteristic. Although quantitative trait loci (QTLs) related to comb size have been identified, molecular mechanisms underlying this trait remain mostly unknown. In this study, RNA sequencing (RNA-seq) was employed to compare whole transcriptomic differences between two groups of Partridge Shank chickens that are divergent in comb sizes. A total of 563 differentially expressed genes (DEGs) were identified, including 277 up-regulated and 286 down-regulated DEGs...
January 31, 2018: Scientific Reports
Sunita Sharma, Dipak Sapkota, Ying Xue, Saroj Rajthala, Mohammed A Yassin, Anna Finne-Wistrand, Kamal Mustafa
BACKGROUND: In bone tissue engineering (BTE), extensive research into vascular endothelial growth factor A (VEGFA)-mediated angiogenesis has yielded inconsistent results. The aim of this study was to investigate the influence on angio- and osteogenesis of adenoviral-mediated delivery of VEGFA alone or in combination with bone morphogenetic protein 2 (BMP2) in bone marrow stromal cells (BMSC) seeded onto a recently developed poly(LLA-co-CL) scaffold. METHODS: Human BMSC were engineered to express VEGFA alone or in combination with BMP2 and seeded onto poly(LLA-co-CL) scaffolds...
January 31, 2018: Stem Cell Research & Therapy
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