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Alberto Ramírez Mata, César Millán Pacheco, José F Cruz Pérez, Martha Minjárez Sáenz, Beatriz E Baca
BACKGROUND: The cyclic-di-GMP (c-di-GMP) second messenger exemplifies a signaling system that regulates many bacterial behaviors of key importance; among them, c-di-GMP controls the transition between motile and sessile life-styles in bacteria. Cellular c-di-GMP levels in bacteria are regulated by the opposite enzymatic activities of diguanylate cyclases and phosphodiesterases, which are proteins that have GGDEF and EAL domains, respectively. Azospirillum is a genus of plant-growth-promoting bacteria, and members of this genus have beneficial effects in many agronomically and ecologically essential plants...
March 9, 2018: BMC Microbiology
Di Zhu, Xue Deng, Xiao-Fei Han, Xiao-Xin Sun, Tao-Wen Pan, Lu-Ping Zheng, Yan-Qiu Liu
Our previous study showed that wedelolactone, a compound isolated from Ecliptae herba , has the potential to enhance osteoblastogenesis. However, the molecular mechanisms by which wedelolactone promoted osteoblastogenesis from bone marrow mesenchymal stem cells (BMSCs) remain largely unknown. In this study, treatment with wedelolactone (2 μg/mL) for 3, 6, and 9 days resulted in an increase in phosphorylation of extracellular signal-regulated kinases (ERKs), c-Jun N -terminal protein kinase (JNK), and p38. Phosphorylation of mitogen-activated protein kinases (MAPKs), ERK and JNK started to increase on day 3 of treatment, and p38 phosphorylation was increased by day 6 of treatment...
March 2, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
E Kague, P E Witten, M Soenens, C L Campos, T Lubiana, S Fisher, C Hammond, K Robson Brown, M R Passos-Bueno, A Huysseune
The capacity to fully replace teeth continuously makes zebrafish an attractive model to explore regeneration and tooth development. The requirement of attachment bone for the appearance of replacement teeth has been hypothesized but not yet investigated. The transcription factor sp7 (osterix) is known in mammals to play an important role during odontoblast differentiation and root formation. Here we study tooth replacement in the absence of attachment bone using sp7 zebrafish mutants. We analysed the pattern of tooth replacement at different stages of development and demonstrated that in zebrafish lacking sp7, attachment bone is never present, independent of the stage of tooth development or fish age, yet replacement is not interrupted...
February 2, 2018: Developmental Biology
Ji-Myung Bae, John C Clarke, Harunur Rashid, Mitra D Adhami, Kayla McCullough, Jordan S Scott, Haiyan Chen, Krishna M Sinha, Benoit de Crombrugghe, Amjad Javed
The Sp7/Osterix transcription factor is essential for bone development. Mutations of Sp7 gene in humans are associated with craniofacial anomalies and osteogenesis imperfecta. However, the role of Sp7 in embryonic tooth development remains unknown. Here we identified the functional requirement of Sp7 for dentin synthesis and tooth development. Sp7-null mice exhibit craniofacial dysmorphogenesis and are completely void of alveolar bone. Surprisingly, initial tooth morphogenesis progressed normally in Sp7-null mice...
February 5, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
Melissa Fiscaletti, Andrew Biggin, Bruce Bennetts, Karen Wong, Julie Briody, Verity Pacey, Catherine Birman, Craig F Munns
Osteogenesis imperfecta (OI) is a connective tissue disorder characterized by low bone density and recurrent fractures with a wide genotypic and phenotypic spectrum. Common features include short stature, opalescent teeth, blue sclerae and hearing impairment. The majority (>90%) of patients with OI have autosomal dominant variants in COL1A1/COL1A2, which lead to defects in type 1 collagen. More recently, numerous recessive variants involving other genes have also been identified. Sp7/Osx gene, is a protein coding gene that encodes a zinc finger transcription factor, osterix, which is a member of the Sp subfamily of sequence-specific DNA-binding proteins...
January 27, 2018: Bone
Hye Jin Kim, Ji Sun Park, Se Won Yi, Hyun Jyung Oh, Jae-Hwan Kim, Keun-Hong Park
The timing of gene transfection greatly influences stem cell differentiation. Sequential transfection is crucial for regulation of cell behavior. When transfected several days after differentiation initiation, genes expressed at the late stage of differentiation can regulate cell behaviors and functions. To determine the optimal timing of key gene delivery, we sequentially transfected human mesenchymal stem cells (hMSCs). This method can easily control osteogenesis of stem cells. hMSCs were first transfected with RUNX2 and SP7 using poly(lactic-co-glycolic acid) nanoparticles to induce osteogenesis, and then with ATF4 after 5, 7, and 14 days...
January 23, 2018: Scientific Reports
Toshihisa Komori
Runx2 is a transcription factor that is essential for osteoblast differentiation and chondrocyte maturation. Ihh, expressed in prehypertrophic and hypertrophic chondrocytes, is required for the specification of Runx2+ osteoprogenitors in endochondral bone development. Runx2 induces Sp7, an essential transcription factor for osteoblast differentiation. Canonical Wnt signaling is also required for osteoblast differentiation. Runx2+ osteoprogenitors retain the capacity to differentiate into chondrocytes, and Sp7 and canonical Wnt signaling direct cells to osteoblasts, thereby inhibiting chondrocyte differentiation...
January 22, 2018: Histochemistry and Cell Biology
Erik A B Hughes, Sophie C Cox, Megan E Cooke, Owen G Davies, Richard L Williams, Thomas J Hall, Liam M Grover
A new bone augmenting material is reported, which is formed from calcium-loaded hydrogel-based spheres. On immersion of these spheres in a physiological medium, they become surrounded with a sheath of precipitate, which ruptures due to a build-up in osmotic pressure. This results in the formation of mineral tubes that protrude from the sphere surface. When brought into close contact with one another, these spheres become fused through the entanglement and subsequent interstitial mineralization of the mineral tubules...
January 11, 2018: Advanced Healthcare Materials
William R Thompson, Sherwin S Yen, Gunes Uzer, Zhihui Xie, Buer Sen, Maya Styner, Keith Burridge, Janet Rubin
The quantity and quality of bone depends on osteoblastic differentiation of mesenchymal stem cells (MSCs), where adipogenic commitment depletes the available pool for osteogenesis. Cell architecture influences lineage decisions, where interfering with cytoskeletal structure promotes adipogenesis. Mechanical strain suppresses MSC adipogenesis partially through RhoA driven enhancement of cytoskeletal structure. To understand the basis of force-driven RhoA activation, we considered critical GEFs (activators) and GAPs (inactivators) on bone marrow MSC lineage fate...
February 2018: Bone
Paul P R Iyyanar, Adil J Nazarali
Cleft palate is one of the most common congenital birth defects worldwide. The homeobox ( Hox ) family of genes are key regulators of embryogenesis, with Hoxa2 having a direct role in secondary palate development. Hoxa2 -/- mice exhibit cleft palate; however, the cellular and molecular mechanisms leading to cleft palate in Hoxa2 -/- mice is largely unknown. Addressing this issue, we found that Hoxa2 regulates spatial and temporal programs of osteogenic differentiation in the developing palate by inhibiting bone morphogenetic protein (BMP) signaling dependent osteoblast markers...
2017: Frontiers in Physiology
Lianyong Liu, Lin Zhou, Xiaorong Yang, Qi Liu, Ling Yang, Chao Zheng, Yongling Zhao, Zhenlin Zhang, Xiaohong Luo
The present study aimed to investigate whether 17β‑estradiol (E2) exerts protective effects on bone deterioration induced by ovariectomy (OVX) through the ephA2/ephrinA2 signaling pathway in rats. Female rats were subjected to OVX, sham surgeryor OVX+E2 treatment. Levels of biomarkers were measured in serum and urine. Hematoxylin and eosin staining was performed on paraffin‑embedded bone sections. Expression of genes and proteins was analyzed by reverse transcription‑quantitative polymerase chain reaction and western blotting, respectively...
January 2018: Molecular Medicine Reports
Dalia Molina-Romero, Antonino Baez, Verónica Quintero-Hernández, Miguel Castañeda-Lucio, Luis Ernesto Fuentes-Ramírez, María Del Rocío Bustillos-Cristales, Osvaldo Rodríguez-Andrade, Yolanda Elizabeth Morales-García, Antonio Munive, Jesús Muñoz-Rojas
Plant growth-promoting rhizobacteria (PGPR) increase plant growth and crop productivity. The inoculation of plants with a bacterial mixture (consortium) apparently provides greater benefits to plant growth than inoculation with a single bacterial strain. In the present work, a bacterial consortium was formulated containing four compatible and desiccation-tolerant strains with potential as PGPR. The formulation had one moderately (Pseudomonas putida KT2440) and three highly desiccation-tolerant (Sphingomonas sp...
2017: PloS One
Paula Suarez-Bregua, Ankur Saxena, Marianne E Bronner, Josep Rotllant
Skeletal development and mineralization are essential processes driven by the coordinated action of neural signals, circulating molecules and local factors. Our previous studies revealed that the novel neuropeptide Pth4, synthesized by hypothalamic cells, was involved in bone metabolism via phosphate regulation in adult zebrafish. Here, we investigate the role of pth4 during skeletal development using single-cell resolution, two-photon laser ablation of Pth4:eGFP-expressing cells and confocal imaging in vivo...
2017: PloS One
Ammar T Qureshi, Devaveena Dey, Erin M Sanders, Jonathan G Seavey, Allison M Tomasino, Kaitlyn Moss, Benjamin Wheatley, David Cholok, Shawn Loder, John Li, Benjamin Levi, Thomas A Davis
A pressing clinical need exists for 63% to 65% of combat-wounded service members and 11% to 20% of civilians who develop heterotopic ossification (HO) after blast-related extremity injury and traumatic injuries, respectively. The mammalian target of rapamycin pathway is a central cellular sensor of injury. We evaluated the prophylactic effects of rapamycin, a selective inhibitor of mammalian target of rapamycin signaling, on HO formation in a rat model of blast-related, polytraumatic extremity injury. Rapamycin was administered intraperitoneally daily for 14 days at 0...
November 2017: American Journal of Pathology
Xing Li, Bei Chang, Banchao Wang, Wenhuan Bu, Liang Zhao, Jie Liu, Lin Meng, Lu Wang, Ying Xin, Dandan Wang, Qi Tang, Changyu Zheng, Hongchen Sun
Chronic periodontitis, a common oral disease, usually results in irreversible bone resorption. Bone regeneration is a complex process between bone‑forming activity of osteoblasts and bone‑resorbing activity of osteoclasts, and still remains a challenge for physicians clinically. A previous study demonstrated that the mechanistic target of rapamycin signaling pathway is involved in osteogenic differentiation of mesenchymal stromal cells. Herein, whether rapamycin could be used to induce osteogenic differentiation of primary bone marrow‑derived mesenchymal stem cells (BMSCs) in vitro and promote new bone formation in vivo were evaluated...
December 2017: Molecular Medicine Reports
Chen-Chen Zhou, Qiu-Chan Xiong, Xin-Xing Zhu, Wen Du, Peng Deng, Xiao-Bing Li, Yi-Zhou Jiang, Shu-Juan Zou, Cun-Yu Wang, Quan Yuan
AFF1 and AFF4 belong to the AFF (AF4/FMR2) family of proteins, which function as scaffolding proteins linking two different transcription elongation factors, positive elongation factor b (P-TEFb) and ELL1/2, in super elongation complexes (SECs). Both AFF1 and AFF4 regulate gene transcription through elongation and chromatin remodeling. However, their function in the osteogenic differentiation of mesenchymal stem cells (MSCs) is unknown. In this study, we show that small interfering RNA (siRNA)-mediated depletion of AFF1 in human MSCs leads to increased alkaline phosphatase (ALP) activity, enhanced mineralization and upregulated expression of osteogenic-related genes...
2017: Bone Research
Yuki Azetsu, Keiji Inohaya, Yoshiro Takano, Masato Kinoshita, Mai Tasaki, Akira Kudo
Sp7 is a zinc finger transcription factor that is essential for osteoblast differentiation in mammals. To verify the characteristic features of osteoblast-lineage cells in teleosts, we established medaka sp7 mutants using a transcription activator-like effector nuclease (TALEN) genome editing system. These mutants showed severe defects in the formation of skeletal structures. In particular, the neural and the hemal arches were not formed, although the chordal centra were formed. Analysis of the transgenic medaka revealed that sp7 mutant had normal distribution of type X collagen a1 a (col10a1a)-positive osteoblast-like cells around the centrum and at the proximal region of the vertebral arch...
November 15, 2017: Developmental Biology
Xiaohui Gu, Xuejie Fu, Jihang Lu, Saijilafu, Bin Li, Zong-Ping Luo, Jianquan Chen
mTORC1 signaling not only plays important physiological roles in the regulation of proliferation and osteogenic differentiation of BMSCs, but also mediates exogenous Wnt-induced protein anabolism and osteoblast differentiation. However, the downstream effectors of the mTORC1 signaling in the above processes are still poorly understood. In this study, we explored the specific role of S6K1, one of the major targets of the mTORC1 pathway, in BMSCs self-renewal and osteogenic differentiation. We first found that S6K1 was active in primary mouse bone marrow stromal cells, and further activated upon osteogenic induction...
January 2018: Journal of Cellular Biochemistry
Phuong T Le, Kathleen A Bishop, David E Maridas, Katherine J Motyl, Daniel J Brooks, Kenichi Nagano, Roland Baron, Mary L Bouxsein, Clifford J Rosen
Misty mice (m/m) have a loss of function mutation in Dock7 gene, a guanine nucleotide exchange factor, resulting in low bone mineral density, uncoupled bone remodeling and reduced bone formation. Dock7 has been identified as a modulator of osteoblast number and in vitro osteogenic differentiation in calvarial osteoblast culture. In addition, m/m exhibit reduced preformed brown adipose tissue innervation and temperature as well as compensatory increase in beige adipocyte markers. While the low bone mineral density phenotype is in part due to higher sympathetic nervous system (SNS) drive in young mice, it is unclear what effect aging would have in mice homozygous for the mutation in the Dock7 gene...
December 2017: Bone
Natalia Artigas, Beatriz Gámez, Mónica Cubillos-Rojas, Cristina Sánchez-de Diego, José Antonio Valer, Gabriel Pons, José Luis Rosa, Francesc Ventura
Osteoblast differentiation is achieved by activating a transcriptional network in which Dlx5, Runx2 and Osx/SP7 have fundamental roles. The tumour suppressor p53 exerts a repressive effect on bone development and remodelling through an unknown mechanism that inhibits the osteoblast differentiation programme. Here we report a physical and functional interaction between Osx and p53 gene products. Physical interaction was found between overexpressed proteins and involved a region adjacent to the OSX zinc fingers and the DNA-binding domain of p53...
December 2017: Cell Death and Differentiation
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