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https://www.readbyqxmd.com/read/28527192/in-vitro-evaluation-of-an-injectable-biphasic-calcium-phosphate-bcp-carrier-system-combined-with-recombinant-human-bone-morphogenetic-protein-rhbmp-9
#1
Masako Fujioka-Kobayashi, Benoit Schaller, Yufeng Zhang, Benjamin E Pippenger, Richard J Miron
Bone morphogenetic protein 9 (BMP9) has previously been characterized as the strongest osteoinductive growth factor among the BMP family. The aim of the present study was to evaluate the possibility of combining rhBMP9 with an injectable biphasic calcium phosphate (I-BCP, maxresorb inject®), since I-BCP is an easy to handle biomaterial with ideal properties for bone augmentation procedures. The adsorption potential of rhBMP9 as well as the cell behavior of bone stromal ST2 cells were investigated on cell viability, adhesion, proliferation and osteogenic differentiation for I-BCP combined with/without rhBMP9 in vitro...
2017: Bio-medical Materials and Engineering
https://www.readbyqxmd.com/read/28494939/cardiosphere-derived-cells-require-endoglin-for-paracrine-mediated-angiogenesis
#2
Rachael E Redgrave, Simon Tual-Chalot, Benjamin J Davison, Esha Singh, Darroch Hall, Muhammad M Amirrasouli, Derek Gilchrist, Alexander Medvinsky, Helen M Arthur
Clinical trials of stem cell therapy to treat ischemic heart disease primarily use heterogeneous stem cell populations. Small benefits occur via paracrine mechanisms that include stimulating angiogenesis, and increased understanding of these mechanisms would help to improve patient outcomes. Cardiosphere-derived-cells (CDCs) are an example of these heterogeneous stem cell populations, cultured from cardiac tissue. CDCs express endoglin, a co-receptor that binds specific transforming growth factor β (TGFβ) family ligands, including bone morphogenetic protein 9 (BMP9)...
May 9, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28470873/bmp9-induces-osteogenesis-and-adipogenesis-in-the-immortalized-human-cranial-suture-progenitors-from-the-patent-sutures-of-craniosynostosis-patients
#3
Dongzhe Song, Fugui Zhang, Russell R Reid, Jixing Ye, Qiang Wei, Junyi Liao, Yulong Zou, Jiaming Fan, Chao Ma, Xue Hu, Xiangyang Qu, Liqun Chen, Li Li, Yichun Yu, Xinyi Yu, Zhicai Zhang, Chen Zhao, Zongyue Zeng, Ruyi Zhang, Shujuan Yan, Tingting Wu, Xingye Wu, Yi Shu, Jiayan Lei, Yasha Li, Wenwen Zhang, Jia Wang, Michael J Lee, Jennifer Moriatis Wolf, Dingming Huang, Tong-Chuan He
The cranial suture complex is a heterogeneous tissue consisting of osteogenic progenitor cells and mesenchymal stem cells (MSCs) from bone marrow and suture mesenchyme. The fusion of cranial sutures is a highly coordinated and tightly regulated process during development. Craniosynostosis is a congenital malformation caused by premature fusion of cranial sutures. While the progenitor cells derived from the cranial suture complex should prove valuable for studying the molecular mechanisms underlying suture development and pathogenic premature suture fusion, primary human cranial suture progenitors (SuPs) have limited life span and gradually lose osteoblastic ability over passages...
May 4, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28470822/pericyte-derived-bone-morphogenetic-protein-4-underlies-white-matter-damage-after-chronic-hypoperfusion
#4
Maiko T Uemura, Masafumi Ihara, Takakuni Maki, Takayuki Nakagomi, Seiji Kaji, Kengo Uemura, Tomohiro Matsuyama, Raj N Kalaria, Ayae Kinoshita, Ryosuke Takahashi
Subcortical small vessel disease (SVD) is characterized by white matter damage resulting from arteriolosclerosis and chronic hypoperfusion. Transforming growth factor beta 1 (TGFB1) is dysregulated in the hereditary SVD, CARASIL (cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy). However, very little is known about the role of the largest group in the TGFB superfamily - the bone morphogenetic proteins (BMPs) - in SVD pathogenesis. The aim of this study was to characterize signaling abnormalities of BMPs in sporadic SVD...
May 4, 2017: Brain Pathology
https://www.readbyqxmd.com/read/28466608/guided-bone-regeneration-with-recombinant-human-bone-morphogenetic-protein-9-loaded-on-either-deproteinized-bovine-bone-mineral-or-a-collagen-barrier-membrane
#5
Nikola Saulacic, Masako Fujioka-Kobayashi, Eizaburo Kobayashi, Benoit Schaller, Richard J Miron
BACKGROUND: Recombinant human bone morphogenetic protein 9 (rhBMP9) has been considered the most osteoinductive growth factor of the BMP-family and has much translation potential for guided bone regeneration (GBR) procedures. PURPOSE: The aim of this study was to compare bone formation using rhBMP9 loaded with different carrier systems including deprotenized bovine bone mineral (BioOss, BO) or collagen barrier membranes (BioGide, BG) in a rabbit GBR model. MATERIALS AND METHODS: rhBMP9 was loaded either on BO; named BO/BMP9, or BG; named BG/BMP9 to investigate the better carrier system for rhBMP9...
May 2, 2017: Clinical Implant Dentistry and related Research
https://www.readbyqxmd.com/read/28447742/bone-morphogenetic-protein-9-stimulates-callus-formation-in-osteoporotic-rats-during-fracture-healing
#6
Xing Wang, Jun Huang, Fan Huang, Jian-Chun Zong, Xi Tang, Yang Liu, Qiong-Fang Zhang, Yang Wang, Liang Chen, Liang-Jun Yin, Bai-Cheng He, Zhong-Liang Deng
Fracture healing involves the coordinated actions of multiple cytokines. Bone morphogenetic protein 9 (BMP9) is an important factor in bone formation. The present study aimed to investigate the osteogenic potential of bone marrow stem cells (BMSCs) in response to adenoviral (Ad)BMP9, and the early fracture repair properties of AdBMP9 in surgically‑created fractures in osteoporotic rats. Alkaline phosphatase (ALP) activity was assayed and matrix mineralization was examined by Alizarin Red S staining. mRNA and protein expression levels of BMP9, runt‑related transcription factor 2 (RUNX2) and type 1 collagen (COL‑1) were detected in vitro and in vivo...
May 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28427181/metformin-inhibits-alk1-mediated-angiogenesis-via-activation-of-ampk
#7
Ying Ying, Takashi Ueta, Shanshan Jiang, Hui Lin, Yuanyuan Wang, Demetrios Vavvas, Rong Wen, Ye-Guang Chen, Zhijun Luo
Anti-VEGF therapy has been proven to be effective in the treatment of pathological angiogenesis. However, therapy resistance often occurs, leading to development of alternative approaches. The present study examines if AMPK negatively regulates ALK1-mediated signaling events and associated angiogenesis. Thus, we treated human umbilical vein endothelial cells with metformin as well as other pharmacological AMPK activators and showed that activation of AMPK inhibited Smad1/5 phosphorylation and tube formation induced by BMP9...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415788/inhibitory-effects-of-bmp9-on-breast-cancer-cells-by-regulating-their-interaction-with-pre-adipocytes-adipocytes
#8
Ting Wang, Zhihui Zhang, Ke Wang, Jinshu Wang, Yayun Jiang, Jing Xia, Liyao Gou, Mengyao Liu, Lan Zhou, Tongchuan He, Yan Zhang
Bone morphogenetic protein 9 (BMP9) possesses multiple functions, but its effects on breast cancer cells in adipose microenvironment are still unclear. This study aimed to investigate whether BMP9 is able to modulate the interaction between pre-adipocytes/adipocytes and breast cancer cells. An in vitro co-culture system was established by using pre-adipocytes/adipocytes and MDA-MB-231 breast cancer cells with BMP9 over-expression. The leptin expression and leptin-induced signaling pathway were evaluated in this co-culture system...
March 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28406027/gelatin-derived-graphene-silicate-hybrid-materials-are-biocompatible-and-synergistically-promote-bmp9-induced-osteogenic-differentiation-of-mesenchymal-stem-cells
#9
Yulong Zou, Nader Taheri Qazvini, Kylie Zane, Monirosadat Sadati, Qiang Wei, Junyi Liao, Jiaming Fan, Dongzhe Song, Jianxiang Liu, Chao Ma, Xiangyang Qu, Liqun Chen, Xinyi Yu, Zhicai Zhang, Chen Zhao, Zongyue Zeng, Ruyi Zhang, Shujuan Yan, Tingting Wu, Xingye Wu, Yi Shu, Yasha Li, Wenwen Zhang, Russell R Reid, Michael J Lee, Jennifer Moritis Wolf, Matthew Tirrell, Tong-Chuan He, Juan J de Pablo, Zhong-Liang Deng
Graphene-based materials are used in many fields but have found only limited applications in biomedicine, including bone tissue engineering. Here, we demonstrate that novel hybrid materials consisting of gelatin-derived graphene and silicate nanosheets of Laponite (GL) are biocompatible and promote osteogenic differentiation of mesenchymal stem cells (MSCs). Homogeneous cell attachment, long-term proliferation, and osteogenic differentiation of MSCs on a GL-scaffold were confirmed using optical microscopy and scanning electron microscopy...
May 4, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28384643/notch-signaling-augments-bmp9-induced-bone-formation-by-promoting-the-osteogenesis-angiogenesis-coupling-process-in-mesenchymal-stem-cells-mscs
#10
Junyi Liao, Qiang Wei, Yulong Zou, Jiaming Fan, Dongzhe Song, Jing Cui, Wenwen Zhang, Yunxiao Zhu, Chao Ma, Xue Hu, Xiangyang Qu, Liqun Chen, Xinyi Yu, Zhicai Zhang, Claire Wang, Chen Zhao, Zongyue Zeng, Ruyi Zhang, Shujuan Yan, Tingting Wu, Xingye Wu, Yi Shu, Jiayan Lei, Yasha Li, Hue H Luu, Michael J Lee, Russell R Reid, Guillermo A Ameer, Jennifer Moriatis Wolf, Tong-Chuan He, Wei Huang
BACKGROUND/AIMS: Mesenchymal stem cells (MSCs) are multipotent progenitors that can differentiate into several lineages including bone. Successful bone formation requires osteogenesis and angiogenesis coupling of MSCs. Here, we investigate if simultaneous activation of BMP9 and Notch signaling yields effective osteogenesis-angiogenesis coupling in MSCs. METHODS: Recently-characterized immortalized mouse adipose-derived progenitors (iMADs) were used as MSC source...
April 4, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28365680/pro-inflammatory-cytokine-tnf-%C3%AE-attenuates-bmp9-induced-osteo-odontoblastic-differentiation-of-the-stem-cells-of-dental-apical-papilla-scaps
#11
Feilong Wang, Ying Jiang, Xia Huang, Qiao Liu, Yan Zhang, Wenping Luo, Fugui Zhang, Pengfei Zhou, Juhong Lin, Hongmei Zhang
BACKGROUND/AIMS: Periapical periodontitis is a common oral disease caused by bacterial invasion of the tooth pulp, which usually leads to local release of pro-inflammatory cytokines and osteolytic lesion. This study is intended to examine the effect of TNF-α on BMP9-induced osteogenic differentiation of the stem cells of dental apical papilla (SCAPs). METHODS: Rat model of periapical periodontitis was established. TNF-α expression was assessed. Osteogenic markers and ectopic bone formation in iSCAPs were analyzed upon BMP9 and TNF-α treatment...
March 31, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28350136/all-trans-retinoic-acid-restored-the-osteogenic-ability-of-bmp9-in-osteosarcoma-through-the-p38-mapk-pathway
#12
Nian Wu, Ruidong Li, Zijun Meng, Mao Nie, Qianzhao Chen, Baicheng He, Zhongliang Deng, Liangjun Yin
Osteosarcoma (OS) is the most common malignant bone tumour and is considered to be a disease caused by a dysfunction in differentiation. Bone morphogenetic protein 9 (BMP9) is the most potent osteogenic factor in mesenchymal stem cells, but it cannot induce osteogenic differentiation in OS cells; this might be one of the determinants in the pathogenesis of OS. All-trans retinoic acid (ATRA) can induce osteogenic differentiation of OS cells and potentiate BMP9-induced osteogenesis in preadipocytes. However, the concomitant effect of ATRA and BMP9 in OS cells is unclear; therefore, in the present study, we focused on this topic...
March 13, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28298363/mutual-interaction-between-endothelial-cells-and-mural-cells-enhances-bmp9-signaling-in-endothelial-cells
#13
Yuki Tachida, Nanae Izumi, Toyo Sakurai, Hideki Kobayashi
Hereditary hemorrhagic telangiectasia is characterized by the formation of abnormal vascular networks and caused by the mutation of genes involved in BMP9 signaling. It is also known that the interaction between endothelial cells (ECs) and mural cells (MCs) is critical to maintain vessel integrity. However, it has not yet fully been uncovered whether the EC-MC interaction affects BMP9 signaling or not. To elucidate this point, we analyzed BMP9 signaling in a co-culture of several types of human primary culture ECs and MCs...
March 15, 2017: Biology Open
https://www.readbyqxmd.com/read/28249039/repair-of-critical-sized-cranial-defects-with-bmp9-transduced-calvarial-cells-delivered-in-a-thermoresponsive-scaffold
#14
Zari P Dumanian, Viktor Tollemar, Jixing Ye, Minpeng Lu, Yunxiao Zhu, Junyi Liao, Guillermo A Ameer, Tong-Chuan He, Russell R Reid
Large skeletal defects caused by trauma, congenital malformations, and post-oncologic resections of the calvarium present major challenges to the reconstructive surgeon. We previously identified BMP-9 as the most osteogenic BMP in vitro and in vivo. Here we sought to investigate the bone regenerative capacity of murine-derived calvarial mesenchymal progenitor cells (iCALs) transduced by BMP-9 in the context of healing critical-sized calvarial defects. To accomplish this, the transduced cells were delivered to the defect site within a thermoresponsive biodegradable scaffold consisting of poly(polyethylene glycol citrate-co-N-isopropylacrylamide mixed with gelatin (PPCN-g)...
2017: PloS One
https://www.readbyqxmd.com/read/28228716/intranasal-bmp9-ameliorates-alzheimer-disease-like-pathology-and-cognitive-deficits-in-app-ps1-transgenic-mice
#15
Zigao Wang, Lu Xiong, Wenbin Wan, Lijie Duan, Xiaojing Bai, Hengbing Zu
Alzheimer's disease (AD) is the most common type of dementia and has no effective therapies. Previous studies showed that bone morphogenetic protein 9 (BMP9), an important factor in the differentiation and phenotype maintenance of cholinergic neurons, ameliorated the cholinergic defects resulting from amyloid deposition. These findings suggest that BMP9 has potential as a therapeutic agent for AD. However, the effects of BMP9 on cognitive function in AD and its underlying mechanisms remain elusive. In the present study, BMP9 was delivered intranasally to 7-month-old APP/PS1 mice for 4 weeks...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28214873/nel-like-molecule-1-nell1-is-regulated-by-bone-morphogenetic-protein-9-bmp9-and-potentiates-bmp9-induced-osteogenic-differentiation-at-the-expense-of-adipogenesis-in-mesenchymal-stem-cells
#16
Jing Wang, Junyi Liao, Fugui Zhang, Dongzhe Song, Minpeng Lu, Jianxiang Liu, Qiang Wei, Shengli Tang, Hao Liu, Jiaming Fan, Yulong Zou, Dan Guo, Jiayi Huang, Feng Liu, Chao Ma, Xue Hu, Li Li, Xiangyang Qu, Liqun Chen, Yaguang Weng, Michael J Lee, Tong-Chuan He, Russell R Reid, Jiye Zhang
BACKGROUND: BMP9 induces both osteogenic and adipogenic differentiation of mesenchymal stem cells (MSCs). Nell1 is a secretory glycoprotein with osteoinductive and anti-adipogenic activities. We investigated the role of Nell1 in BMP9-induced osteogenesis and adipogenesis in MSCs. METHODS: Previously characterized MSCs iMEFs were used. Overexpression of BMP9 and NELL1 or silencing of mouse Nell1 was mediated by adenoviral vectors. Early and late osteogenic and adipogenic markers were assessed by staining techniques and qPCR analysis...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28213819/conditional-knockout-of-activin-like-kinase-1-alk-1-leads-to-heart-failure-without-maladaptive-remodeling
#17
Kevin J Morine, Xiaoying Qiao, Vikram Paruchuri, Mark J Aronovitz, Emily E Mackey, Lyanne Buiten, Jonathan Levine, Keshan Ughreja, Prerna Nepali, Robert M Blanton, Richard H Karas, S Paul Oh, Navin K Kapur
Activin like kinase-1 (AlK-1) mediates signaling via the transforming growth factor beta (TGFβ) family of ligands. AlK-1 activity promotes endothelial proliferation and migration. Reduced AlK-1 activity is associated with arteriovenous malformations. No studies have examined the effect of global AlK-1 deletion on indices of cardiac remodeling. We hypothesized that reduced levels of AlK-1 promote maladaptive cardiac remodeling. To test this hypothesis, we employed AlK-1 conditional knockout mice (cKO) harboring the ROSA26-CreER knock-in allele, whereby a single dose of intraperitoneal tamoxifen triggered ubiquitous Cre recombinase-mediated excision of floxed AlK-1 alleles...
May 2017: Heart and Vessels
https://www.readbyqxmd.com/read/28125843/pituitary-adenylate-cyclase-activating-peptide-pacap-a-novel-secretagogue-regulates-secreted-morphogens-in-newborn-rat-retina
#18
Monika Lakk, Viktoria Denes, Karmen Kovacs, Orsolya Hideg, Bence F Szabo, Robert Gabriel
Purpose: Pituitary adenylate cyclase-activating peptide (PACAP)1-38 has been reported to be responsible for regulation of a disparate array of developmental processes in the central nervous system, and its antiapoptotic effect has been revealed in numerous models, pointing to its relevance in the etiology of neurodegenerative disorders. However, its function in retinal development remains unclear. Here, we aimed to point out that versatility can be achieved through interaction with other regulators, in which PACAP can act indirectly on the retinal microenvironment...
January 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28103025/identification-of-the-first-selective-activin-receptor-like-kinase-1-inhibitor-a-reversible-version-of-l-783277
#19
Hanna Cho, Sandip Sengupta, Sean S H Jeon, Wooyoung Hur, Hwan Geun Choi, Hong-Seog Seo, Byung Joo Lee, Jeong Hun Kim, Minhwan Chung, Noo Li Jeon, Nam Doo Kim, Taebo Sim
We synthesized 1 (San78-130), a reversible version of L-783277, as a selective and potent ALK1 inhibitor. Our study showed that 1 possesses great kinase selectivity against a panel of 342 kinases and more potent activity against ALK1 than L-783277. Among the six ALK isotypes (ALK1-6), ALK1 is most significantly inhibited by compound 1. Compound 1 suppresses the BMP9-induced Smad1/5 pathway by mainly inhibiting ALK1 in C2C12 cells. Our molecular dynamics simulations suggest that H-bonding interaction between the C-4' hydroxyl group of 1 and Arg334 of ALK1 substantially contributes to the ALK1 inhibition...
February 6, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28052093/bone-morphogenetic-protein-9-enhances-osteogenic-differentiation-of-human-periodontal-ligament-stem-cells-via-the-jnk-pathway
#20
Pei Wang, Yanen Wang, Weizhong Tang, Xingxing Wang, Yanan Pang, Su Yang, Yibo Wei, Haochen Gao, Dalin Wang, Zhizhong Cao
Bone morphogenetic protein-9 (BMP9) shows great osteoinductive potential in bone regeneration. Periodontal ligament stem cells (PDLSCs) with multi-differentiation capability and low immunogenicity are increasingly used as seed cells for periodontal regenerative therapies. In the present study, we investigated the potent osteogenic activity of BMP9 on human PDLSCs (hPDLSCs), in which the c-Jun N-terminal kinase (JNK) pathway is possibly involved. Our results showed that JNK inhibition by the specific inhibitor SP600125 or adenovirus expressing small interfering RNA (siRNA) targeting JNK (AdR-si-JNK) significantly decreased BMP9-induced gene and protein expression of early and late osteogenic markers, such as runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP), osteopontin (OPN), and osteocalcin (OCN), in hPDLSCs...
2017: PloS One
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