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Osteoblast Molecular mechanisms

Hongya Guan, Guowei Shang, Yuanbo Cui, Jiu Liu, Xiaoya Sun, Wei Cao, Yisheng Wang, Yuebai Li
A growing amount of evidence has shown that long noncoding RNAs (lncRNAs) play crucial roles in osteosarcoma (OS). However, little knowledge is available about the functional roles and molecular mechanisms of lncRNA Alu-mediated p21 transcriptional regulator (APTR) in OS. Herein, APTR expression was demonstrated to be significantly upregulated in OS tumor tissues and four OS cell lines (including MG63, 143B, Saos-2, and HOS) compared with the adjacent tissues and human osteoblast cell line hFOB1.19, respectively...
October 14, 2018: Journal of Cellular Physiology
Luna Ge, Yazhou Cui, Kai Cheng, Jinxiang Han
Isopsoralen (IPRN), one of the main effective ingredients in Psoralea corylifolia Linn, has a variety of biological effects, including antiosteoporotic effects. In vivo studies show that IPRN can increase bone strength and trabecular bone microstructure in a sex hormone deficiency-induced osteoporosis model. However, the mechanism underlying this osteogenic potential has not been investigated in detail. In the present study, we investigated the molecular mechanism of IPRN-induced osteogenesis in MC3T3-E1 cells...
October 11, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Naoya Tsukune, Masako Naito, Akiko Ohashi, Tadashi Ninomiya, Shuichi Sato, Tomihisa Takahashi
Nuclear protein, lamin A, which is a component of inner membrane on nucleoplasm, plays a role in nuclear formation and cell differentiation. The expression of mutated lamin A, termed progerin, causes a rare genetic aging disorder, Hutchinson-Gilford progeria syndrome, which shows abnormal bone formation with the decrease in a number of osteoblasts and osteocytes. However, exact molecular mechanism how progerin exerts depressive effects on osteogenesis has not been fully understood. Here, we created mouse lamin A dC50 cDNA encoding progerin that lacks 50 amino acid residues at C-terminus, transfected it in mouse preosteoblast-like MC3T3-E1 cells, and examined the changes in osteoblast phenotype...
October 3, 2018: Cell and Tissue Research
Marc N Wein
Osteocytes are the most abundant cell type in bone and play a central role in orchestrating skeletal remodeling, in part by producing paracrine-acting factors that in turn influence osteoblast and osteoclast activity. Recent evidence has indicated that osteocytes are crucial cellular targets of parathyroid hormone (PTH). Here, we will review the cellular and molecular mechanisms through which PTH influences osteocyte function. Two well-studied PTH target genes in osteocytes are SOST and receptor activator of NF-κB ligand (RANKL)...
January 2018: JBMR Plus
Eva Svandova, Barbora Vesela, Hervé Lesot, Jeremy Sadoine, Anne Poliard, Eva Matalova
FasL is a well-known actor in the apoptotic pathways but recent reports have pointed to its important novel roles beyond cell death, as observed also for bone cells. This is supported by non-apoptotic appearance of FasL during osteogenesis and by significant bone alterations unrelated to apoptosis in FasL deficient ( gld ) mice. The molecular mechanism behind this novel role has not yet been revealed. In this report, intramembranous bone, where osteoblasts differentiate directly from mesenchymal precursors without intermediary chondrogenic step, was investigated...
2018: Frontiers in Physiology
Yangyang Cao, Haoqing Yang, Luyuan Jin, Juan Du, Zhipeng Fan
Bone marrow mesenchymal stem cells (BMSCs) nowadays are regarded as promising candidates in cell-based therapy for the regeneration of damaged bone tissues that are either incurable or intractable due to the insufficiency of current therapies. Recent studies suggest that BMSCs differentiate into osteoblasts, and that this differentiation is regulated by some specific patterns of epigenetic modifications, such as DNA methylation. However, the potential role of DNA methylation modification in BMSC osteogenic differentiation is unclear...
2018: Stem Cells International
Laura Hyväri, Miina Ojansivu, Miia Juntunen, Kimmo Kartasalo, Susanna Miettinen, Sari Vanhatupa
Adipose tissue is an attractive stem cell source for soft and bone tissue engineering applications and stem cell therapies. The adipose-derived stromal/stem cells (ASCs) have a multilineage differentiation capacity that is regulated through extracellular signals. The cellular events related to cell adhesion and cytoskeleton have been suggested as central regulators of differentiation fate decision. However, the detailed knowledge of these molecular mechanisms in human ASCs remains limited. This study examined the significance of focal adhesion kinase (FAK), Rho-Rho-associated protein kinase (Rho-ROCK), and their downstream target extracellular signal-regulated kinase 1/2 (ERK1/2) on hASCs differentiation towards osteoblasts and adipocytes...
2018: Stem Cells International
Yusuke Nomura, Chie Fukui, Yuki Morishita, Yuji Haishima
Introduction: Multipotent mesenchymal stem cells (MSCs) are widespread in adult organisms and are implicated in tissue maintenance and repair, regulation of hematopoiesis, and immunologic responses. Human (h)MSCs have applications in tissue engineering, cell-based therapy, and medical devices but it is unclear how they respond to unfavorable conditions, such as hypoxia or inflammation after transplantation in vivo . Although endotoxin testing is required for evaluating the quality and safety of transplanted MSCs, no reports on their dose response to endotoxins are available to establish the limits for in vitro MSC culture systems...
June 2018: Regenerative Therapy
Celio J da Costa Fernandes, Fábio J B Bezerra, Bruno de Campos Souza, Mônica Aparecida Campos, Willian Fernando Zambuzzi
Titanium is widely used for biomedical applications, but little information is being delivered regarding the cellular/molecular mechanisms explaining their efficacy, mainly considering the effects of the Ti-released trace elements on pre-osteoblasts. We addressed this issue by investigating decisive intracellular signal transduction able to modulate cytoskeleton rearrangement, proliferative phenotype and extracellular matrix (ECM) remodeling. We considered titanium grades IV and V, submitted or not to dual acid-etching (w/DAE or wo/DAE, respectively)...
December 2018: Journal of Trace Elements in Medicine and Biology
Shujuan Yan, Ruyi Zhang, Ke Wu, Jing Cui, Shifeng Huang, Xiaojuan Ji, Liping An, Chengfu Yuan, Cheng Gong, Linghuan Zhang, Wei Liu, Yixiao Feng, Bo Zhang, Zhengyu Dai, Yi Shen, Xi Wang, Wenping Luo, Bo Liu, Rex C Haydon, Michael J Lee, Russell R Reid, Jennifer Moriatis Wolf, Qiong Shi, Hue H Luu, Tong-Chuan He, Yaguang Weng
Mesenchymal stem cells (MSCs) are multipotent stem cells and capable of differentiating into multiple cell types including osteoblastic, chondrogenic and adipogenic lineages. We previously identified BMP9 as one of the most potent BMPs that induce osteoblastic differentiation of MSCs although exact molecular mechanism through which BMP9 regulates osteogenic differentiation remains to be fully understood. Here, we seek to develop a recombinant adenovirus system to optimally silence mouse BMP9 and then characterize the important role of BMP9 in osteogenic differentiation of MSCs...
June 2018: Genes & Diseases
Tim Rolvien, Mike Barbeck, Sabine Wenisch, Michael Amling, Matthias Krause
Bone grafts, i.e., autologous, allogeneic or synthetic bone substitute materials play an increasing role in reconstructive orthopedic surgery. While the indications and materials differ, it is important to understand the cellular mechanisms regarding their integration and remodeling, which are discussed in this review article. Osteoconductivity describes the new bone growth on the graft, while osteoinductivity represents the differentiation of undifferentiated cells into bone forming osteoblasts. The best case is that both mechanisms are accompanied by osteogenesis, i...
September 23, 2018: International Journal of Molecular Sciences
Penghong Dong, Xiaochuan Gu, Guiling Zhu, Ming Li, Bin Ma, Ying Zi
The function of melatonin (MLT) in promoting fracture healing has been demonstrated in previous studies. However, the molecular mechanism underlying therapeutic effects of MLT is not entirely clear. In this study, mesenchymal stem cells (MSCs) were isolated from rat bone marrow and identified by flow cytometry. We found that MLT treatment upregulated the neuropeptide Y (NPY) and NPY receptor Y1 (NPY1R) expression, and promoted the proliferation and migration of MSCs, which was suppressed by BIBP3226, an inhibitor of NPY1R...
September 18, 2018: Pharmacology
Dana M Otzel, Christine F Conover, Fan Ye, Ean G Phillips, Taylor Bassett, Russell D Wnek, Micah Flores, Andrea Catter, Payal Ghosh, Alexander Balaez, Jason Petusevsky, Cong Chen, Yongxin Gao, Yi Zhang, Jessica M Jiron, Prodip K Bose, Stephen E Borst, Thomas J Wronski, J Ignacio Aguirre, Joshua F Yarrow
To elucidate mechanisms of bone loss after spinal cord injury (SCI), we evaluated the time-course of cancellous and cortical bone microarchitectural deterioration via microcomputed tomography, measured histomorphometric and circulating bone turnover indices, and characterized the development of whole bone mechanical deficits in a clinically relevant experimental SCI model. 16-weeks-old male Sprague-Dawley rats received T9 laminectomy (SHAM, n = 50) or moderate-severe contusion SCI (n = 52). Outcomes were assessed at 2-weeks, 1-month, 2-months, and 3-months post-surgery...
September 14, 2018: Calcified Tissue International
Wing Ying Chow, Chris J Forman, Dominique Bihan, Anna M Puszkarska, Rakesh Rajan, David G Reid, David A Slatter, Lucy J Colwell, David J Wales, Richard W Farndale, Melinda J Duer
Fibrillar collagens have mechanical and biological roles, providing tissues with both tensile strength and cell binding sites which allow molecular interactions with cell-surface receptors such as integrins. A key question is: how do collagens allow tissue flexibility whilst maintaining well-defined ligand binding sites? Here we show that proline residues in collagen glycine-proline-hydroxyproline (Gly-Pro-Hyp) triplets provide local conformational flexibility, which in turn confers well-defined, low energy molecular compression-extension and bending, by employing two-dimensional 13 C-13 C correlation NMR spectroscopy on 13 C-labelled intact ex vivo bone and in vitro osteoblast extracellular matrix...
September 14, 2018: Scientific Reports
Yan Chen, Alison Aiken, Sanjay Saw, Ashley Weiss, Hui Fang, Rama Khokha
Deregulated proteolysis invariably underlies most human diseases including bone pathologies. Metalloproteinases constitute the largest of the five protease families, and the metzincin metalloproteinases are inhibited by the four tissue inhibitors of metalloproteinase called TIMPs. We hypothesized that Timp genes are essential for skeletal homeostasis. We bred individual Timp knockout mice to generate unique mouse models, the quadruple Timp null strain (QT) as well as mice harboring only a single Timp3 allele (QT3+/- )...
September 14, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
Lei Yang, Gaopeng Guan, Lanjie Lei, Qizhuang Lv, Shengyuan Liu, Xiuwen Zhan, Zhenzhen Jiang, Xiang Gu
Palmitic acid (PA) is the most common saturated long-chain fatty acid in food that causes cell apoptosis. However, little is known about the molecular mechanisms of PA toxicity. In this study, we explore the effects of PA on proliferation and apoptosis in human osteoblast-like Saos-2 cells and uncover the signaling pathways involved in the process. Our study showed that endoplasmic reticulum (ER) stress and autophagy are involved in PA-induced Saos-2 cell apoptosis. We found that PA inhibited the viability of Saos-2 cells in a dose- and time-dependent manner...
September 7, 2018: Cell Stress & Chaperones
Zheng Jing, Changyuan Wang, Qining Yang, Xuelian Wei, Yue Jin, Qiang Meng, Qi Liu, Zhihao Liu, Xiaodong Ma, Kexin Liu, Huijun Sun, Mozhen Liu
Glucocorticoid-induced osteoporosis (GIO) is a secondary osteoporosis with extensive use of glucocorticoids (GCs). GCs can increase bone fragility and fracture via inhibiting osteoblastic proliferation and differentiation. Luteolin (LUT), a kind of plant flavonoid, has been reported to exhibit the antioxidant activity, but the effects of LUT on GIO still remain unclear. This study aimed to investigate the effects of LUT on GIO both in vivo and in vitro and elaborate the potential molecular mechanisms. LUT increased the superoxide dismutase activity, glutathione level and decreased reactive oxygen species (ROS) level and lactate dehydrogenase release in GIO...
September 7, 2018: Journal of Cellular Physiology
Haibo Tong, Chunlin Zou, Siyuan Qin, Jie Meng, Evan T Keller, Jian Zhang, Yi Lu
Prostate cancer preferentially metastasizes to the bone. However, the underlying molecular mechanisms are still unclear. To explore the effects of a bone-mimicking microenvironment on PC3 prostate cancer cell growth and metastasis, we used osteoblast differentiation medium (ODM; minimal essential medium alpha supplemented with L-ascorbic acid) to mimic the bone microenvironment. PC3 cells grown in ODM underwent epithelial-mesenchymal transition and showed enhanced colony formation, migration, and invasion abilities compared to the cells grown in normal medium...
September 6, 2018: Journal of Biomedical Research
Elena Tsourdi, Katharina Jähn, Martina Rauner, Björn Busse, Lynda F Bonewald
Osteocytes, the most abundant bone cell in the adult skeleton, can function as mechanosensors directing osteoblast and osteoclast function in order to maintain optimal load bearing bone in addition to functioning as endocrine cells regulating phosphate metabolism. A controversial function, previously overlooked or denied, has been osteocytes as regulators of calcium metabolism. Early histologists upon observing enlarged osteocyte lacunae in bone sections proposed that mature osteocytes could remove their perilacunar matrix, a term called "osteocytic osteolysis"...
September 1, 2018: Journal of Musculoskeletal & Neuronal Interactions
Mayumi Iguchi, Miki Hiroi, Haruhide Kanegae, Yoshihiro Ohmori
During chronic inflammation from diseases, such as periodontal disease, the proinflammatory cytokines interferon-gamma (IFN γ ) and tumor necrosis factor- α (TNF α ) alter bone remodeling. To elucidate the underlying molecular mechanisms, we investigated the effect of IFN γ and TNF α on the proliferation and survival of clonal MC3T3-E1 mouse osteoblasts. We found that although IFN γ or TNF α alone affected cell growth and survival only marginally, costimulation with both synergistically inhibited cell growth and reduced cell viability...
2018: Mediators of Inflammation
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