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Osteoblast Molecular mechanisms

Laurent Beck
Under normal physiological condition, the biomineralization process is limited to skeletal tissues and teeth and occurs throughout the individual's life. Biomineralization is an actively regulated process involving the progressive mineralization of the extracellular matrix secreted by osteoblasts in bone or odontoblasts and ameloblasts in tooth. Although the detailed molecular mechanisms underlying the formation of calcium-phosphate apatite crystals are still debated, it is suggested that calcium and phosphate may need to be transported across the membrane of the mineralizing cell, suggesting a pivotal role of phosphate transporters in bone and tooth mineralization...
December 3, 2018: Pflügers Archiv: European Journal of Physiology
Thanintorn Yodthong, Ureporn Kedjarune-Leggat, Carl Smythe, Rapepun Wititsuwannakul, Thanawat Pitakpornpreecha
Osteoporosis is widely recognized as a major health problem caused by an inappropriate rate of bone resorption compared to bone formation. Previously we showed that d-pinitol inhibits osteoclastogenesis but has no effect on osteoblastogenesis. However, the effect on osteoblast differentiation of its isomer, l-quebrachitol, has not yet been reported. The purpose of this study was, therefore, to investigate whether l-quebrachitol promotes the osteoblastogenesis of pre-osteoblastic MC3T3-E1 cells. Moreover, the molecular mechanism of action of l-quebrachitol was further explored...
November 26, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Tetsu Kawabata, Haruhiko Tokuda, Go Sakai, Kazuhiko Fujita, Rie Matsushima-Nishiwaki, Gen Kuroyanagi, Takanobu Otsuka, Osamu Kozawa
Heat shock protein 70 (HSP70) is a ubiquitously expressed molecular chaperone in a variety of cells including osteoblasts. We previously showed that insulin-like growth factor-I (IGF-I) elicits migration of osteoblast-like MC3T3-E1 cells through the activation of phosphatidylinositol 3-kinase/Akt and p44/p42 mitogen-activated protein (MAP) kinase. In the present study, we investigated the effects of HSP70 inhibitors on the IGF-I-elicited migration of these cells and the mechanism involved. The IGF-I-stimulated osteoblast migration evaluated by a wound-healing assay and by a transwell cell migration was significantly reduced by VER-155008 and YM-08, which are both HSP70 inhibitors...
November 21, 2018: Biomedicines
Xiaobing Yu, Wei Huang, Dewei Zhao, Ke Yang, Lili Tan, Xiuzhi Zhang, Junlei Li, Meng Zhang, Shuo Zhang, Tao Liu, Baolin Wu, Mingjia Qu, Ruimeng Duan, Yashuai Yuan
Low molecular weight poly-lactic acid (PLLA) is a polymer matrix of orthopaedic implants. The PLLA matrix incorporating bioactive magnesium ion (Mg2+ ) enhances bone regeneration. But the optimal ratio of Mg2+ to PLLA matrix has not been well reported and is worthy of study. We synthesized silane-coated Mg/PLLA composites containing 1%, 2%, 3%, 4% and 5% Mg micro-particles. The mechanical properties, in vitro cytocompatibility, cell viability and osteogenesis differentiation and in vivo performance of silane-coated Mg/PLLA composites were evaluated...
October 23, 2018: Colloids and Surfaces. B, Biointerfaces
Antonios N Gargalionis, Efthimia K Basdra, Athanasios G Papavassiliou
Distorted mechanotransduction represents the molecular hallmark of disease mechanobiology and is displayed with common features during the development of various pathophysiologies. Polycystins constitute a family of mechanosensitive proteins that facilitate pathogenic signal transduction mechanisms. The main representatives of the family are polycystin-1 (PC1) and polycystin-2 (PC2), which function as a mechano-induced membrane receptor and a calcium-permeable ion channel, respectively. PC1 and PC2 mediate extracellular mechanical stimulation, induce intracellular molecular signaling and evoke corresponding gene transcription...
November 21, 2018: Journal of Cellular Biochemistry
Vinal Menon, Joy Lincoln
Heart valves are dynamic, highly organized structures required for unidirectional blood flow through the heart. Over an average lifetime, the valve leaflets or cusps open and close over a billion times, however in over 5 million Americans, leaflet function fails due to biomechanical insufficiency in response to wear-and-tear or pathological stimulus. Calcific aortic valve disease (CAVD) is the most common valve pathology and leads to stiffening of the cusp and narrowing of the aortic orifice leading to stenosis and insufficiency...
2018: Frontiers in Cardiovascular Medicine
Hao-Yang Mi, Xin Jing, Galip Yilmaz, Breanna S Hagerty, Eduardo Enriquez, Lih-Sheng Turng
Mimicking the mechanical properties of native tissues is a critical criterion for an ideal tissue engineering scaffold. However, most biodegradable synthetic materials, including polyester-based polyurethanes (PUs), consist of rigid polyester chains and have high crystallinity. They typically lack the elasticity of most human tissues. In this study, a new type of biodegradable PU with excellent elasticity was synthesized based on the controlled crosslinking of poly(ester ether) triblock copolymer diols and polycaprolactone (PCL) triols using urethane linkages...
September 15, 2018: Chemical Engineering Journal
Xin Qin, Qing Jiang, Toshihiro Miyazaki, Toshihisa Komori
Cleidocranial dysplasia (CCD, #119600), which is characterized by hypoplastic clavicles, open fontanelles, supernumerary teeth, and a short stature, is caused by heterozygous mutations in RUNX2. However, it currently remains unclear why suture closure is severely impaired in CCD patients. The closure of posterior frontal (PF) and sagittal (SAG) sutures was completely interrupted in Runx2+/- mice, and the proliferation of suture mesenchymal cells and their condensation were less than those in wild-type mice...
November 16, 2018: Human Molecular Genetics
Jin Seok Park, Minbeom Kim, No-Joon Song, Jun-Hyeong Kim, Dongyeob Seo, Ji-Hyung Lee, Su Myung Jung, Jae Young Lee, Jaewon Lee, Youn Sook Lee, Kye Won Park, Seok Hee Park
Mesenchymal stem cells (MSCs) are multipotent cells that can differentiate into mature cells of various cell types. Although the differentiation process of MSCs requires lineage-specific transcription factors, the exact molecular mechanism that determine MSCs differentiation is not clearly addressed. Here, we demonstrate a Smad4-Taz axis as a new intrinsic regulator for adipo-osteogenic differentiation of MSCs and show that this function of Smad4 is independent of the TGF-β signal. Smad4 directly bound to the Taz protein and facilitated nuclear localization of Taz through its nuclear localization signal (NLS)...
November 16, 2018: Stem Cells
Urszula Kędzierska, Łukasz Banasiak, Paweł Kiela, Paweł Marek Majewski
Although loss of bone mineral density is a common symptom of chronic inflammatory diseases, its mechanisms are still poorly understood. The PHEX gene encodes a Zn-endopeptidase expressed in osteoblasts and contributes to bone mineralization. Data derived from rodents has indicated co-repression of the PHEX gene by the NF-κB pathway and poly(ADP-ribose) polymerase 1 (PARP1). The aim of this study was to determine the molecular mechanism involved in TNF-mediated downregulation of PHEX expression in human osteoblasts and human osteosarcoma cell line...
November 15, 2018: Acta Biochimica Polonica
Aira Matsugaki, Tatsuki Harada, Yumi Kimura, Aiko Sekita, Takayoshi Nakano
Bone metastasis is one of the most intractable bone diseases; it is accompanied with a severe mechanical dysfunction of bone tissue. We recently discovered that the disorganized collagen/apatite microstructure in cancer-bearing bone is a dominant determinant of the disruption of bone mechanical function; disordered osteoblast arrangement was found to be one of the principal determinants of the deteriorated collagen/apatite microstructure. However, the precise molecular mechanisms regulating the disordered osteoblast arrangement triggered by cancer invasion are not yet understood...
November 5, 2018: International Journal of Molecular Sciences
Duanjing Chen, Yuanyuan Gong, Ling Xu, Mengjiao Zhou, Jie Li, Jinlin Song
Through loss- and gain-of-function experiments in knockout and transgenic mice, Forkhead box O (FOXO) family transcription factors have been demonstrated to play essential roles in many biological processes, including cellular proliferation, apoptosis and differentiation. Osteogenic differentiation from mesenchymal stem cells (MSCs) into osteoblasts is a well-organized process that is carefully guided and characterized by various factors, such as runt-related transcription factor 2 (Runx2), β-catenin, osteocalcin (OCN), alkaline phosphatase (ALP) and activating transcription factor 4 (ATF4)...
November 5, 2018: Cell Proliferation
Zhiyu Yuan, Kaveh Memarzadeh, Abish S Stephen, Robert P Allaker, Robert A Brown, Jie Huang
Magnetic stimulation has been applied to bone regeneration, however, the cellular and molecular mechanisms of repair still require a better understanding. A three-dimensional (3D) collagen model was developed using plastic compression, which produces dense, cellular, mechanically strong native collagen structures. Osteoblast cells (MG-63) and magnetic iron oxide nanoparticles (IONPs) were incorporated into collagen gels to produce a range of cell-laden models. A magnetic bio-reactor to support cell growth under static magnetic fields (SMFs) was designed and fabricated by 3D printing...
November 2, 2018: Scientific Reports
Hua Liu, Wei Wei, Xiaojian Wang, Xiaojun Guan, Qingqing Chen, Zhongjin Pu, Xudong Xu, Aichun Wei
Osteosarcoma (OS) is the most common primary malignant bone tumor and the third most common cancer that occurs during childhood and adolescence. Increasing evidence has suggested that microRNA (miR)‑23b‑3p has an important role in OS tumorigenesis; however, the underlying molecular mechanisms remain unknown. The aim of the present study was to investigate the expression levels of miR‑23b‑3p and sine oculis homeobox homolog 1 (SIX1) in OS tissues and cell lines (MG‑63, SaOS‑2 and U2OS), as well as to observe the effects of miR‑23b‑3p on U2OS cell viability, cell cycle, apoptosis and invasive ability...
December 2018: Molecular Medicine Reports
Xiaomeng Zhang, Huaning Xie, Pan Chang, Huishou Zhao, Yunlong Xia, Ling Zhang, Xiong Guo, Chong Huang, Feng Yan, Lang Hu, Chen Lin, Yueyang Li, Zhenyu Xiong, Xiong Wang, Guohua Li, Longxiang Deng, Shan Wang, Ling Tao
Smooth muscle cells (SMCs), which form the walls of blood vessels, play an important role in vascular development and the pathogenic process of vascular remodeling. However, the molecular mechanisms governing SMC differentiation remain poorly understood. Glycoprotein M6B (GPM6B) is a four-transmembrane protein that belongs to the proteolipid protein family and is widely expressed in neurons, oligodendrocytes, and astrocytes. Previous studies have revealed that GPM6B plays a role in neuronal differentiation, myelination, and osteoblast differentiation...
October 29, 2018: Stem Cells
Xu Zhou, Ying-Hua Qiu, Pei He, Fei Jiang, Long-Fei Wu, Xin Lu, Shu-Feng Lei, Fei-Yan Deng
A large number of SNPs significant for osteoporosis (OP) had been identified by genome-wide association studies. However, the underlying association mechanisms were largely unknown. From the perspective of protein phosphorylation, gene expression regulation, and bone cell activity, this study aims to illustrate association mechanisms for representative SNPs of interest. We utilized public databases and bioinformatics tool to identify OP-associated SNPs which potentially influence protein phosphorylation (phosSNPs)...
October 28, 2018: Journal of Cellular and Molecular Medicine
Bing Wang, Xing-Long Qu, Jiaxiang Liu, Junhui Lu, Zong-Yu Zhou
Long noncoding RNAs (lncRNAs) have drawn increasing attention because of the role which they play in various diseases, including osteosarcoma. So far, the function and mechanism of HOTAIR in osteosarcoma are unclear. In our study, we observed that HOTAIR was elevated accompanied with a decrease of miR-217 and an increase of ZEB1 in human osteosarcoma cells including U2OS, MG63, Saos-2, and SW1353 compared with human osteoblast cell line hFOB. In addition, the subsequent functional assay exhibited that silencing HOTAIR could significantly repress osteosarcoma cell growth, migration, invasion, and induce cell apoptosis capacity, which indicated that HOTAIR exerted an oncogenic role in osteosarcoma...
October 26, 2018: Journal of Cellular Physiology
Akira Takahashi, Mieradili Mulati, Masanori Saito, Hoashi Numata, Yutaka Kobayashi, Hiroki Ochi, Shingo Sato, Philipp Kaldis, Atsushi Okawa, Hiroyuki Inose
Bone mass is maintained by a balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption. Although recent genetic studies have uncovered various mechanisms that regulate osteoblast differentiation, the molecular basis of osteoblast proliferation remains unclear. Here, using an osteoblast-specific loss-of-function mouse model, we demonstrate that cyclin-dependent kinase 1 (Cdk1) regulates osteoblast proliferation and differentiation. qRT-PCR analyses revealed that Cdk1 is highly expressed in bone  and is down-regulated upon osteoblast differentiation...
October 26, 2018: Journal of Biological Chemistry
Lihua Peng, Dianming Jiang
Resveratrol shows potent anti-tumor therapeutic properties in various tumors. However, the exact effect of resveratrol on osteosarcoma cells, especially cancer stem cells, remains unclear. In this study, we examined the effect of resveratrol on osteosarcoma stem cells and explored the underlying molecular mechanisms. Resveratrol inhibited cell viability, self-renewal ability and tumorigenesis of osteosarcoma cells, whereas showed no significant inhibition effects to normal osteoblast cells. Mechanically, resveratrol treatment decreased cytokines synthesis and inhibited JAK2/STAT3 signaling, which was consistent with the decline of cancer stem cells marker, CD133...
2018: PloS One
Sonia Vallet, Julia-Marie Filzmoser, Martin Pecherstorfer, Klaus Podar
Bone disease, including osteolytic lesions and/or osteoporosis, is a common feature of multiple myeloma (MM). The consequences of skeletal involvement are severe pain, spinal cord compressions, and bone fractures, which have a dramatic impact on patients' quality of life and, ultimately, survival. During the past few years, several landmark studies significantly enhanced our insight into MM bone disease (MBD) by identifying molecular mechanisms leading to increased bone resorption due to osteoclast activation, and decreased bone formation by osteoblast inhibition...
October 24, 2018: Pharmaceutics
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