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Osteoblast Molecular mechanisms

Dan Wang, Xinhao Jiang, Aiqing Lu, Min Tu, Wei Huang, Ping Huang
Bone marrow mesenchymal stem cells (BMSCs) are pluripotent cells, which have the capacity to differentiate into various types of mesenchymal cell phenotypes, including osteoblasts, chondroblasts, myoblasts and tendon fibroblasts (TFs). The molecular mechanism for tenogenic differentiation of BMSCs is still unknown. The present study investigated the effects of bone morphogenetic protein (BMP) 14 on BMSC differentiation in vitro . It was revealed that BMP14 significantly increased the expression of tendon markers (scleraxis and tenomodulin) at the mRNA and protein level, which led to the upregulation of sirtuin 1 (Sirt1) expression...
August 2018: Experimental and Therapeutic Medicine
Heng Li, Guofeng Tian, Feipeng Tian, Lin Shao
Taurine upregulated gene 1 (TUG1), a long non-coding RNA (lncRNA), has recently been suggested to be associated with the development of osteosarcoma (OS), but the underlying molecular mechanism still remains largely unclear. In the present study, it was revealed that TUG1 was significantly upregulated whereas miR-212-3p was significantly downregulated in OS tissues and cell lines, when compared with adjacent non-tumor tissues and normal osteoblasts cell lines, respectively. An inverse association between the TUG1 and miR-212-3p expression was also observed in OS tissues...
August 2018: Experimental and Therapeutic Medicine
Jose R Perez, Dimitrios Kouroupis, Deborah J Li, Thomas M Best, Lee Kaplan, Diego Correa
Bone fractures and segmental bone defects are a significant source of patient morbidity and place a staggering economic burden on the healthcare system. The annual cost of treating bone defects in the US has been estimated to be $5 billion, while enormous costs are spent on bone grafts for bone injuries, tumors, and other pathologies associated with defective fracture healing. Autologous bone grafts represent the gold standard for the treatment of bone defects. However, they are associated with variable clinical outcomes, postsurgical morbidity, especially at the donor site, and increased surgical costs...
2018: Frontiers in Bioengineering and Biotechnology
Youqiang Sun, Vincent Kuek, Yuhao Liu, Jennifer Tickner, Yu Yuan, Leilei Chen, Zhikui Zeng, Min Shao, Wei He, Jiake Xu
MiR-214 belongs to a family of microRNA (small, highly conserved noncoding RNA molecules) precursors that play a pivotal role in biological functions, such as cellular function, tissue development, tissue homeostasis, and pathogenesis of diseases. Recently, miR-214 emerged as a critical regulator of musculoskeletal metabolism. Specifically, miR-214 can mediate skeletal muscle myogenesis and vascular smooth muscle cell proliferation, migration, and differentiation. MiR-214 also modulates osteoblast function by targeting specific molecular pathways and the expression of various osteoblast-related genes; promotes osteoclast activity by targeting phosphatase and tensin homolog (Pten); and mediates osteoclast-osteoblast intercellular crosstalk via an exosomal miRNA paracrine mechanism...
August 4, 2018: Journal of Cellular Physiology
Shaofeng An
Calcium ions (Ca2+ ) is the main element of dental pulp capping materials. Ca 2+ signaling plays a crucial role in a myriad of cell activities. An overwhelming array of studies have already reported the experimental and clinical benefits of Ca2+ -enriched materials in the treatment of teeth with accidental vital pulp exposure and incomplete root formation. Thus, Ca2+ signaling has always been an excellent target for the design of various novel biomaterials for use in revitalizing or regenerative endodontic procedures...
August 1, 2018: Journal of Cellular Physiology
Kazuhiko Fujita, Takanobu Otsuka, Tetsu Kawabata, Shingo Kainuma, Go Sakai, Rie Matsushima-Nishiwaki, Osamu Kozawa, Haruhiko Tokuda
Heat shock protein 90 (HSP90), expressed abundantly in a variety of cell types, is a molecular chaperone, and has a central role in protein homeostasis under stress conditions. In our previous study, it was shown that thrombin stimulates interleukin‑6 (IL‑6) synthesis via p44/p42 mitogen‑activated protein kinase (MAPK) and p38 MAPK in osteoblast‑like MC3T3‑E1 cells, and that Rho‑kinase acts as a positive regulator at a point upstream of p38 MAPK, but not p44/p42 MAPK. The present study investigated whether or not HSP90 is involved in the thrombin‑stimulated synthesis of IL‑6 and examined the mechanism by which HSP90 is involved in MC3T3‑E1 cells...
October 2018: International Journal of Molecular Medicine
Sabrina Ehnert, Caren Linnemann, Romina H Aspera-Werz, Daria Bykova, Sara Biermann, Leonie Fecht, Peter M De Zwart, Andreas K Nussler, Fabian Stuby
The cytokines secreted by immune cells have a large impact on the tissue, surrounding a fracture, e.g., by attraction of osteoprogenitor cells. However, the underlying mechanisms are not yet fully understood. Thus, this study aims at investigating molecular mechanisms of the immune cell-mediated migration of immature primary human osteoblasts (phOBs), with transforming growth factor beta (TGF-β), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 ( NOX4 ) and focal adhesion kinase (FAK) as possible regulators...
July 31, 2018: International Journal of Molecular Sciences
Mingna Li, Xiaoyun Wu, Xian Guo, Pengjia Bao, Xuezhi Ding, Min Chu, Chunnian Liang, Ping Yan
Background: The practice of dehorning yak raises animal safety concerns, which have been addressed by selective breeding to obtain genetically hornless yak. The POLLED locus in yak has been studied extensively; however, little is known regarding the proteins that regulate horn bud development. Methods: A differential proteomic analysis was performed to compare the skin from the horn bud region of polled yak fetuses and the horn bud tissue of horned yak fetuses using isobaric tags for relative and absolute quantitation (iTRAQ) technology coupled with 2D LC-MS/MS...
2018: Proteome Science
Rasime Kalkan, Pinar Tulay
Osteoporosis is a major health issue, especially in older women. The absence of estrogen is the main cause of menopausal osteoporosis. Estrogen and androgen hormones play major roles during the growth and development of the skeletal system, including preservation of bone structure. Estrogen plays an important role in the balance between the bone formation of osteoblasts and osteoclasts, which are associated with bone resorption. Several pathways have been shown to regulate bone formation and degradation. Estrogen and Ephrin-Eph pathways are among the most important molecular mechanisms that regulate bone reconstruction...
2018: Critical Reviews in Eukaryotic Gene Expression
Lei Wang, Yu Chai, Changjun Li, Haiyun Liu, Weiping Su, Xiaonan Liu, Bing Yu, Weiqi Lei, Bin Yu, Janet L Crane, Xu Cao, Mei Wan
Low-density lipoprotein receptor-related protein 6 (LRP6) is a co-receptor for Wnt signaling and can be recruited by multiple growth factors/hormones to their receptors facilitating intracellular signaling activation. The ligands that bind directly to LRP6 have not been identified. Here, we report that bioactive oxidized phospholipids (oxPLs) are native ligands of LRP6, but not the closely related LRP5. oxPLs are products of lipid oxidation involving in pathological conditions such as hyperlipidemia, atherosclerosis, and inflammation...
2018: Bone Research
Yanqin Li, Bin Bai, Yaohui Zhang
Recently, more and more studies indicate that iron overload would cause osteopenia or osteoporosis. However, the molecular mechanism of it remains unclear. Moreover, very little is known about the iron metabolism in bone tissue at present. Therefore, the mRNA expression of iron-regulators, transferrin receptor1 (Tfr1), divalent metal transporter1 (Dmt1 + IRE and Dmt1 - IRE), ferritin (FtH and FtL), and ferroportin1 (Ireg1), and the localization of ferroportin1 protein were examined in the bone tissue of rats...
July 19, 2018: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
Young Jae Moon, Chi-Young Yun, Hwajung Choi, Jung Ryul Kim, Byung-Hyun Park, Eui-Sic Cho
Corticalization, coalescence of trabecular bone into the metaphyseal cortex, is important for the longitudinal growth of long bones. However, little is known about the molecular mechanisms controlling corticalization. To understand the molecular mechanisms underlying corticalization, we analyzed osteoblast-specific Osterix-knockout mice (Col-OMT). In control mice, corticalization was initiated after 7 postnatal days, and the number of osteoblasts in the peripheral spongiosa was increased compared to the number in the central spongiosa...
July 18, 2018: Experimental & Molecular Medicine
Yufa Wang, Jieun Kim, Andrea Chan, Cari Whyne, Diane Nam
T lymphocytes and pro-inflammatory cytokines, specifically interleukin-17F (IL-17F) have been identified as important regulators in bone regeneration during fracture repair. To better understand the molecular mechanisms of IL-17F-mediated osteoblastogenesis, a mouse pre-osteoblast cell line (MC3T3-E1) was utilized to characterize the intracellular signal transduction of IL-17F. Comparisons to the established canonical Wnt signaling pathway were made using Wnt3a ligand. Our results demonstrated greater bone marker gene expression in IL-17F-treated cells, compared to cells treated with Wnt3a...
July 17, 2018: Bone
Shuangli Zhang, Baolin Li, Wei Tang, Linying Ni, Huili Ma, Ming Lu, Qinggang Meng
Previous studies have demonstrated that connective tissue growth factor (CTGF) is expressed at increased levels in prostate cancer bone metastasis mouse models and patients with prostate cancer which metastasizes to the bone; however, the underlying molecular mechanism(s) remain unknown. The present study investigated the function of CTGF in osteoblast differentiation and its effect on prostate cancer bone metastasis by analyzing CTGF gene expression and transcription at different levels of invasion, metastasis of prostate cancer cells, and the influence of CTGF on proliferation and xenotransplantation...
August 2018: Oncology Letters
Jumpei Kida, Kenji Hata, Eriko Nakamura, Hiroko Yagi, Yoshifumi Takahata, Tomohiko Murakami, Yoshinobu Maeda, Riko Nishimura
Canonical Wnt signalling plays an important role in osteoblast differentiation and bone formation. However, the molecular mechanisms by which canonical Wnt signalling exerts its osteoblastogenic effect remain elusive. Here, we investigated the relationship between lymphoid enhancer-binding factor 1 (LEF1) and transcriptional co-activator with PDZ-binding motif (TAZ), both of which are transcriptional regulators that mediate canonical Wnt signalling during osteoblast differentiation. Reporter assay and co-immunoprecipitation experiments revealed functional and physical interaction between LEF1 and TAZ...
July 10, 2018: Scientific Reports
Yu Lin, Lili Xiao, Yiyuan Zhang, Ping Li, Yinsheng Wu, Yanping Lin
BACKGROUND: Understanding of the molecular mechanisms of miRNAs involved in osteoblast differentiation is important for the treatment of bone-related diseases. METHODS: MC3T3-E1 cells were induced to osteogenic differentiation by culturing with bone morphogenetic protein 2 (BMP2). After transfected with miR-26b-3p mimics or inhibitors, the osteogenic differentiation of MC3T3-E1 cells was detected by ALP and ARS staining. Cell viability was analyzed by MTT. The expressions of miR-26b-3p and osteogenic related markers and signaling were examined by qPCR and western blot...
July 5, 2018: Genomics
Aimy Sebastian, Nicholas R Hum, Cesar Morfin, Deepa K Murugesh, Gabriela G Loots
Wnt16 is a major Wnt ligand involved in the regulation of postnatal bone homeostasis. Previous studies have shown that Wnt16 promotes bone formation and inhibits bone resorption, suggesting that this molecule could be targeted for therapeutic interventions to treat bone thinning disorders such as osteoporosis. However, the molecular mechanisms by which Wnt16 regulates bone metabolism is not yet fully understood. To better understand the molecular mechanisms by which Wnt16 promotes bone formation and to identify the target genes regulated by Wnt16 in osteoblasts, we treated calvarial osteoblasts purified from C57Bl/6 mice with recombinant Wnt16 and profiled the gene expression changes by RNA-seq at 24 h post-treatment...
July 5, 2018: Gene
Xiao Chen, Xin Zhi, Zhifeng Yin, Xiaoqun Li, Longjuan Qin, Zili Qiu, Jiacan Su
Bone metabolism is determined by a delicate balance between bone resorption by osteoclasts and bone formation by osteoblasts. The imbalance due to over-activated osteoclasts plays an important role in various diseases. Activation of NF-κB and MAPK signaling pathways by receptor activator of nuclear factor -κB ligand (RANKL) is vital for osteoclastogenesis. Here, we for the first time explored the effects of 18β-glycyrrhetinic acid (18β-GA), a pentacyclic triterpenoid found in the Glycyrrhiza glabra L roots, on RANKL-induced osteoclastogenesis, osteoclast functions and signaling pathways in vitro and in vivo ...
2018: Frontiers in Pharmacology
Y L Hou, J Q Ling, C C Chen, J J Quan, Y Du
Objective: To examine the expression of naked cuticle homolog 2 (Nkd2) in the process of root development and osteogenic differentiation of dental follicle cells of rat (rDFC), in order to explore the molecular mechanisms of Nkd2 on the osteoblast differentiation of rDFCs. Methods: Immunohistochemical analysis was used to detect the expression of Nkd2 in the base dental follicle of the mandibular first molar of rat at 1, 3, 5, 7, 9, 11 and 13 days postnatal. Mineralization nodule formation of rDFCs was detected by alizarin red staining and cetylpyridine...
July 9, 2017: Zhonghua Kou Qiang Yi Xue za Zhi, Zhonghua Kouqiang Yixue Zazhi, Chinese Journal of Stomatology
Scott Taylor, Rong Hu, Efrain Pacheco, Kathrin Locher, Ian Pyrah, Michael S Ominsky, Rogely Waite Boyce
Inhibition of sclerostin with sclerostin antibody (Scl-Ab) results in stimulation of bone formation on cancellous (Cn), endocortical (Ec), and periosteal (Ps) surfaces in rodents and non-human primates. With long-term dosing of Scl-Ab, the increase in bone formation is not sustained, attenuating first on Cn surfaces and later on Ec and Ps surfaces. In Cn bone, the attenuation in bone formation (self-regulation) is associated with transcriptional changes in the osteocyte (OCy) that would limit mitogenesis and are sustained with continued dosing...
June 2018: Bone Reports
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