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U Chae, N-R Park, E-S Kim, J-Y Choi, M Yim, H-S Lee, S-R Lee, S Lee, J-W Park, D-S Lee
Spinal deformities such as scoliosis and kyphosis are incurable, and can lead to decreased physical function, pain, and reduced quality of life. Despite much effort, no clear therapies for the treatment of these conditions have been found. Therefore, the development of an animal model for spinal deformity would be extremely valuable to our understanding of vertebral diseases. In this study, we demonstrate that mice deficient in the mitochondrial enzyme isocitrate dehydrogenase 2 (IDH2) develop spinal deformities with aging...
March 12, 2018: Physiological Research
Mao Li, Xi Chen, Jinku Yan, Long Zhou, Yifan Wang, Fan He, Jun Lin, Caihong Zhu, Guoqing Pan, Jia Yu, Ming Pei, Huilin Yang, Tao Liu
Decellularized extracellular matrix (ECM) derived from stem cells has been shown as a promising biomaterial for bone regeneration because of the promotion effect on osteogenesis in mesenchymal stem cells (MSCs). However, bone regeneration is also influenced by bone resorption and little is known about the effect of cell-derived ECM on osteoclast differentiation. In this study, ECM was deposited by MSCs and, after decellularization, the effect of ECM on osteoclastogenesis of bone marrow monocytes (BMMs) was investigated in comparison to standard tissue culture polystyrene...
March 8, 2018: Acta Biomaterialia
S Jerez, S Díaz-Infante, B Chen
In this work, we model osteoclast-osteoblast population dynamics with random environmental fluctuations in order to understand the random variations of the bone remodeling process in real life. For this purpose, we construct a stochastic differential model for the interactions between the osteoclast and osteoblast cell populations using the parameter perturbation technique. We prove the existence of a globally attractive positive unique solution for the stochastically perturbed system. Also, the stochastic boundedness of the solution is demonstrated using its p-th order moments for p ≥ 1...
March 8, 2018: Mathematical Biosciences
Elisa Boanini, Paola Torricelli, Felix Sima, Emanuel Axente, Milena Fini, Ion N Mihailescu, Adriana Bigi
The chemistry, structure and morphology of the implant surface have a great influence on the integration of an implant material with bone tissue. In this work, we applied Combinatorial Matrix-Assisted Pulsed Laser Evaporation (C-MAPLE) to deposit gradient thin films with variable compositions of Sr-substituted hydroxyapatite (SrHA) and Zn-substituted β-tricalcium phosphate (ZnTCP) on Titanium substrates. Five samples with different SrHA/ZnTCP composition ratios were fabricated by a single step laser procedure...
March 6, 2018: Journal of Inorganic Biochemistry
Anna Teti, Steven L Teitelbaum
Bone and marrow are the two facets of the same organ, in which bone and hematopoietic cells coexist and interact. Marrow and skeletal tissue influence each-other and a variety of genetic disorders directly targets both of them, which may result in combined hematopoietic failure and skeletal malformations. Other conditions primarily affect one organ with secondary influences on the other. For instance, various forms of congenital anemias reduce bone mass and induce osteoporosis, while osteoclast failure in osteopetrosis prevents marrow development reducing medullary cavities and causing anemia and pancytopenia...
March 6, 2018: Bone
Mei Liu, Xiaotian Zhou, Lin Zhou, Zhenzhou Liu, Jinbo Yuan, Jianwen Cheng, Jinmin Zhao, Longfei Wu, Hui Li, Haiwen Qiu, Jiake Xu
The discovery of new therapeutic drugs with the ability of preventing inflammation and joint destruction with less adverse effects is urgently needed for rheumatoid arthritis (RA). Carnosic acid (CA), a major phenolic compound isolated from the leaves of Rosemary (Rosmarinus officinalis L.), has been reported to have antioxidative and antimicrobial properties. However, its effects on RA have not been elucidated. Here, we investigated the effects of CA on osteoclasts and fibroblast-like synoviocytes in vitro and on collagen-induced arthritis (CIA) in Wistar rats in vivo...
March 9, 2018: Journal of Cellular Physiology
Martina Blaschke, Regine Koepp, Julia Cortis, Marina Komrakova, Matthias Schieker, Ute Hempel, Heide Siggelkow
BACKGROUND: Crohn´s disease (CD) is associated with a higher prevalence of osteoporosis. The pathogenesis of bone affliction remains controversial, especially if inflammatory cytokines or glucocorticoid therapy are the main contributors. In postmenopausal osteoporosis, bone resorption is induced by IL-6, IL-1β and TNF-α. In contrast, in children with CD, IL-6 exclusively decreased bone formation without affecting bone resorption. OBJECTIVES: The objective of this study was to further clarify the pathophysiology of bone affliction in adult patients with CD with the use of an osteoblast and osteoclast cell model...
January 2018: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
Yan Zhang, Nidhi Rohatgi, Deborah J Veis, Joel Schilling, Steven L Teitelbaum, Wei Zou
Osteoclasts are mitochondria-rich cells, but the role of these energy-producing organelles in bone resorption is poorly defined. To this end, we conditionally deleted the mitochondria-inducing co-activator, PGC1β, in myeloid lineage cells to generate PGC1βLysM mice. In contrast to previous reports, PGC1β-deficient macrophages differentiate normally into osteoclasts albeit with impaired resorptive function due to cytoskeletal disorganization. Consequently, bone mass of PGC1βLysM mice is double that of wild type...
March 8, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
Ryan L Wong, Sarah Hiyari, Aline Yaghsezian, Mina Davar, Maísa Casarin, Yi-Ling Lin, Sotirios Tetradis, Paulo M Camargo, Flavia Q Pirih
BACKGROUND: Peri-implantitis is an inflammatory response to bacterial biofilm resulting in bone loss and can ultimately lead to implant failure. Due to the lack of predictable treatments available, a thorough understanding of peri-implantitis's pathogenesis is essential. The objective of this study is to evaluate and compare the response of acute induced peri-implantitis and periodontitis lesions after insult removal. METHODS: Implants were placed in one-month-old C57BL/6J male mice eight weeks post extraction of their left maxillary molars...
February 19, 2018: Journal of Periodontology
Zhe-Kun Jia, Hai-Yun Li, Yu-Lin Liang, Lawrence Albert Potempa, Shang-Rong Ji, Yi Wu
C-reactive protein (CRP) is an established marker of rheumatoid arthritis (RA) but with ill-defined actions in the pathogenesis. Here, we show that CRP regulates the differentiation of osteoclasts, a central mediator of joint inflammation and bone erosion in RA, in a conformation- and receptor activator of NF-κB ligand (RANKL)-dependent manner. CRP in the native conformation is ineffective, whereas the monomeric conformation (mCRP) actively modulates osteoclast differentiation through NF-κB and phospholipase C signaling...
2018: Frontiers in Immunology
Mithun Ghosh, In Sook Kim, Young Min Lee, Seong Min Hong, Taek Hwan Lee, Ji Hong Lim, Trishna Debnath, Beong Ou Lim
This study aimed to determine the anti-osteoclastogenic effects of extracts from Aronia melanocarpa 'Viking' (AM) and identify the underlying mechanisms in vitro. Reactive oxygen species (ROS) are signal mediators in osteoclast differentiation. AM extracts inhibited ROS production in RAW 264.7 cells in a dose-dependent manner and exhibited strong radical scavenging activity. The extracts also attenuated the number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated osteoclasts. To attain molecular insights, the effect of the extracts on the signaling pathways induced by receptor activator of nuclear factor kappa B ligand (RANKL) were also investigated...
March 8, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Qiang Wang, Jian Mo, Chenchen Zhao, Kangmao Huang, Mingxuan Feng, Wenxin He, Jiying Wang, Shuai Chen, Zi'ang Xie, Jianjun Ma, Shunwu Fan
Bone metastasis is a severe complication of advanced breast cancer, resulting in osteolysis and increased mortality in patients. Raddeanin A (RA), isolated from traditional Chinese herbs, is an oleanane-type triterpenoid saponin with anticancer potential. In this study, we investigated the effects of RA in breast cancer-induced osteolysis and elucidated the possible mechanisms involved in this process. We first verified that RA could suppress osteoclast formation and bone resorption in vitro. Next, we confirmed that RA suppressed Ti-particle-induced osteolysis in a mouse calvarial model, possibly through inhibition of the SRC/AKT signaling pathway...
March 7, 2018: Cell Death & Disease
Andrew L Durham, Mei Y Speer, Marta Scatena, Cecilia M Giachelli, Catherine M Shanahan
Vascular calcification is associated with a significant increase in all-cause mortality and atherosclerotic plaque rupture. Calcification has been determined to be an active process driven in part by vascular smooth muscle cell (VSMC) transdifferentiation within the vascular wall. Historically, VSMC phenotype switching has been viewed as binary, with the cells able to adopt a physiological contractile phenotype or an alternate 'synthetic' phenotype in response to injury. More recent work, including lineage tracing has however revealed that VSMCs are able to adopt a number of phenotypes, including calcific (osteogenic, chondrocytic, and osteoclastic), adipogenic, and macrophagic phenotypes...
March 15, 2018: Cardiovascular Research
H M Steinkamp, J D Hathaway-Schrader, M B Chavez, J D Aartun, L Zhang, T Jensen, A Shojaee Bakhtiari, K L Helke, D J Stumpo, A V Alekseyenko, C M Novince, P J Blackshear, K L Kirkwood
Tristetraprolin (TTP) is an RNA-binding protein that targets numerous immunomodulatory mRNA transcripts for degradation. Many TTP targets are key players in the pathogenesis of periodontal bone loss, including tumor necrosis factor-α. To better understand the extent that host immune factors play during periodontal bone loss, we assessed alveolar bone levels, inflammation and osteoclast activity in periodontal tissues, and immune response in draining cervical lymph nodes in TTP-deficient and wild-type (WT) mice in an aging study...
March 1, 2018: Journal of Dental Research
Chris Steffi, Dong Wang, Chee Hoe Kong, Zuyong Wang, Poon Nian Lim, Zhilong Shi, Eng San Thian, Wilson Wang
Estrogen, a steroid hormone, plays an important role in modulating osteoclast proliferation and development. Estrogen deficiency boosts osteoclast activity, leading to osteoporosis in elderly women. In this study, 17-ß estradiol (E2) loaded poly(ε-caprolactone) (PCL)/silk fibroin (SF) electrospun microfibers was developed as a proposed localized E2 delivery system to treat osteoporotic fractures. PCL is a synthetic polymer known for its biocompatibility and excellent mechanical properties. The bioactivity of PCL was enhanced by mixing it with natural silk fibroin (SF) polymer that has low immunogenicity and inherent bioactivity...
March 7, 2018: ACS Applied Materials & Interfaces
Xiao Zheng, Wen Kang, Huihui Liu, Shanyu Guo
It is abundantly clear that tumor-derived parathyroid hormone-related protein (PTHrP), receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG) are central contributors in promoting osteolytic process of breast carcinoma bone metastasis. Forcusing on this molecular basis, the study was undertaken to explore the inhibition effects of total flavonoids from Scutellaria barbata D. Don (TF-SB) on human breast carcinoma bone metastasis. MDA-MB-231 cells and nude mouse models of breast cancer bone metastasis were given TF-SB in different concentrations...
February 27, 2018: International Journal of Molecular Medicine
Gang Luo, Fangfei Li, Xiaoming Li, Zheng-Guo Wang, Bo Zhang
Although tumor necrosis factor alpha (TNF‑α) is known to serve a critical role in the pathogenesis of inflammatory osteolysis, the exact mechanisms underlying the effects of TNF‑α on osteoclast recruitment and differentiation remain unclear. To investigate the mechanisms by which TNF‑α influences osteoclast differentiation, mouse bone marrow‑derived macrophages (BMMs) were used as osteoclast precursors, and osteoclastogenesis was induced by macrophage colony‑stimulating factor and receptor activator of nuclear factor (NF)‑κB ligand (RANKL) with or without TNF‑α for 4 days...
March 7, 2018: Molecular Medicine Reports
Hanlin Yao, Zhen Yao, Shaocheng Zhang, Wenjun Zhang, Wen Zhou
Osteoporosis is a disease that significantly influences life expectancy and quality in humans. Oxidative stress may stimulate bone marrow osteoclast differentiation and inhibit osteoblast (OB) differentiation. OB proliferation and differentiation are affected by the forkhead box O (FoxO)1/β‑catenin signaling pathway. The osteogenic differentiation of mesenchymal stem cells (MSCs) may be promoted by silent information regulator type‑1 [sirtuin (SIRT)1]. However, the molecular mechanism of SIRT1 regulation of osteogenic differentiation of MSCs remains unclear, and further elucidation is needed...
March 1, 2018: Molecular Medicine Reports
Junichi Kikuta, Masaru Ishii
Bone is continually remodeled by bone-resorbing osteoclasts and bone-forming osteoblasts. Although it has long been believed that bone homeostasis is tightly regulated by communication between osteoclasts and osteoblasts, the fundamental process and dynamics have remained elusive. We originally established an advanced imaging system to visualize living bone tissues using intravital two-photon microscopy. By means of this system, we revealed the in vivo behavior of bone-resorbing osteoclasts and bone-forming osteoblasts in bone tissues...
2018: Clinical Calcium
Tomoki Nakashima
Recent studies of mouse genetics and human gene mutations has greatly contributed to clarifying the molecular mechanism of bone metabolism. Bone is constantly renewed by the balanced action of osteoblastic bone formation and osteoclastic bone resorption both of which mainly occur at the bone surface. This restructuring process called "bone remodeling" is important not only for normal bone mass and strength, but also for mineral homeostasis. Bone remodeling is stringently regulated by communication among bone component cells such as osteoclasts, osteoblasts, osteocytes and endothelial cells...
2018: Clinical Calcium
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