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https://www.readbyqxmd.com/read/29353057/mechanisms-of-enhanced-osteoclastogenesis-in-alkaptonuria
#1
Giacomina Brunetti, Albina Tummolo, Gabriele D'Amato, Alberto Gaeta, Federica Ortolani, Laura Piacente, Paola Giordano, Silvia Colucci, Maria Grano, Francesco Papadia, Maria Felicia Faienza
Alkaptonuria (AKU) is a rare disorder characterized by the deficiency of the enzyme homogentisate 1,2-dioxygenase and consequent homogentisate accumulation, which leads to progressive and severe osteoarthopathy starting from the second decade of life. Thus, in AKU patients bone involvement represents an important clinical issue, which we investigated. Serum levels of RANKL, osteoprotegerin, sclerostin, DKK1, and bone remodeling markers were measured in nine AKU patients (two children and seven adults) and 22 controls, together with lumbar spine bone mineral density (LS-BMD) and femoral-BMD...
January 15, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29353038/cereblon-crbn-deletion-reverses-streptozotocin-induced-diabetic-osteoporosis-in-mice
#2
Cong Yao, Xiong Guo, Wan-Xia Yao, Chun Zhang
Diabetes mellitus is a major cause to induce osteoporosis. Though the pathogenesis of osteoporosis progression has been well investigated, its still not fully understood. Recently, cereblon (CRBN) was considered as a negative modulator of adenosine monophosphate-activated protein kinase (AMPK) in vitro and in vivo. Here, we presented results indicating that CRBN could effectively regulate osteoporosis development. In STZ-induced wild type (WT) mice with diabetes, the osteoclasts were highly increased along with the deterioration of bone structure...
January 15, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29352112/direct-cell-cell-contact-between-mature-osteoblasts-and-osteoclasts-dynamically-controls-their-functions-in-vivo
#3
Masayuki Furuya, Junichi Kikuta, Sayumi Fujimori, Shigeto Seno, Hiroki Maeda, Mai Shirazaki, Maki Uenaka, Hiroki Mizuno, Yoriko Iwamoto, Akito Morimoto, Kunihiko Hashimoto, Takeshi Ito, Yukihiro Isogai, Masafumi Kashii, Takashi Kaito, Shinsuke Ohba, Ung-Il Chung, Alexander C Lichtler, Kazuya Kikuchi, Hideo Matsuda, Hideki Yoshikawa, Masaru Ishii
Bone homeostasis is regulated by communication between bone-forming mature osteoblasts (mOBs) and bone-resorptive mature osteoclasts (mOCs). However, the spatial-temporal relationship and mode of interaction in vivo remain elusive. Here we show, by using an intravital imaging technique, that mOB and mOC functions are regulated via direct cell-cell contact between these cell types. The mOBs and mOCs mainly occupy discrete territories in the steady state, although direct cell-cell contact is detected in spatiotemporally limited areas...
January 19, 2018: Nature Communications
https://www.readbyqxmd.com/read/29351359/cyr61-ccn1-regulates-sclerostin-levels-and-bone-maintenance
#4
Gexin Zhao, Bau-Lin Huang, Diana Rigueur, Weiguang Wang, Chimay Bhoot, Kemberly R Charles, Jongseung Baek, Subburaman Mohan, Jie Jiang, Karen M Lyons
CYR61/CCN1 is a matricellular protein that resides in the extracellular matrix, but serves regulatory rather than structural roles. CYR61/CCN1 is found in mineralized tissues and has been shown to influence bone healing in vivo and osteogenic differentiation in vitro. In this study we generated Cyr61 bone specific knockout mice to examine the physiological role of CYR61/CCN1 in bone development and maintenance in vivo. Extensive analysis of Cyr61 conditional knockout mice showed a significant decrease in both trabecular and cortical bone mass as compared to WT littermate...
January 19, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/29348675/stac2-negatively-regulates-osteoclast-formation-by-targeting-the-rank-signaling-complex
#5
Eutteum Jeong, Han Kyoung Choi, Jin Hee Park, Soo Young Lee
The receptor activator of nuclear factor-κB (RANK) protein activates various protein kinase signaling cascades, including those involving NF-κB, mitogen-activated protein kinase (MAPK), and Bruton tyrosine kinase (Btk)/tyrosine-protein kinase Tec. However, the mechanism underlying the negative regulation of RANK by downstream signaling molecules remains unclear. Here, we report that Src homology 3 domain and cysteine-rich domain-containing protein 2 (STAC2) is a novel RANK ligand-inducible protein that negatively regulates RANK-mediated osteoclast formation...
January 18, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29348610/the-histone-methyltransferase-dot1l-inhibits-osteoclastogenesis-and-protects-against-osteoporosis
#6
Yanpan Gao, Wei Ge
Osteoclasts are absorptive cells that play a critical role in homeostatic bone remodeling and pathological bone resorption. Emerging evidence suggests an important role of epigenetic regulation in osteoclastogenesis. In this study, we investigated the role of DOT1L, which regulates gene expression epigenetically by histone H3K79 methylation (H3K79me), during osteoclast formation. Using RANKL-induced RAW264.7 macrophage cells as an osteoclast differentiation model, we found that DOT1L and H3K79me2 levels were upregulated during osteoclast differentiation...
January 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29348535/umbilical-cord-extracts-improve-osteoporotic-abnormalities-of-bone-marrow-derived-mesenchymal-stem-cells-and-promote-their-therapeutic-effects-on-ovariectomised-rats
#7
Akira Saito, Kanna Nagaishi, Kousuke Iba, Yuka Mizue, Takako Chikenji, Miho Otani, Masako Nakano, Kazusa Oyama, Toshihiko Yamashita, Mineko Fujimiya
Bone marrow-derived mesenchymal stem cells (BM-MSCs) are the most valuable source of autologous cells for transplantation and tissue regeneration to treat osteoporosis. Although BM-MSCs are the primary cells responsible for maintaining bone metabolism and homeostasis, their regenerative ability may be attenuated in postmenopausal osteoporosis patients. Therefore, we first examined potential abnormalities of BM-MSCs in an oestrogen-deficient rat model constructed by ovariectomy (OVX-MSCs). Cell proliferation, mobilisation, and regulation of osteoclasts were downregulated in OVX-MSCs...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348072/structure-based-development-of-an-osteoprotegerin-like-glycopeptide-that-blocks-rankl-rank-interactions-and-reduces-ovariectomy-induced-bone-loss-in-mice
#8
Chao Liu, Xiao Chen, Xin Zhi, Weizong Weng, Quan Li, Xiang Li, Yan Zou, Jiacan Su, Hong-Gang Hu
Osteoporosis is a metabolic bone disease characterized by low bone mass and micro-architectural deterioration of bone, for which the underlying mechanism is an imbalance between bone resorption and bone remodeling. The protein-protein interactions between receptor activator of nuclear factor-κB ligand (RANKL), RANK (its receptor), and osteoprotegerin (OPG), are known to mediate the development and activation of osteoclasts in bone remodeling, and are regarded as a pivotal therapeutic target for the treatment of osteoporosis...
January 10, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29346788/vitamin-d-classic-and-novel-actions
#9
Ángel Gil, Julio Plaza-Diaz, María Dolores Mesa
BACKGROUND: Classically, vitamin D has been implicated in bone health by promoting calcium absorption in the gut and maintenance of serum calcium and phosphate concentrations, as well as by its action on bone growth and reorganization through the action of osteoblasts and osteoclasts cells. However, in the last 2 decades, novel actions of vitamin D have been discovered. The present report summarizes both classic and novel actions of vitamin D. SUMMARY: 1,25(OH)2 vitamin D, the active metabolite of vitamin D, also known as calcitriol, regulates not only calcium and phosphate homeostasis but also cell proliferation and differentiation, and has a key a role to play in the responses of the immune and nervous systems...
January 18, 2018: Annals of Nutrition & Metabolism
https://www.readbyqxmd.com/read/29345352/achyranthes-bidentata-polysaccharide-suppresses-osteoclastogenesis-and-bone-resorption-via-inhibiting-rankl-signaling
#10
Dezhi Song, Zhen Cao, Song Huang, Jennifer Tickner, Nan Li, Heng Qiu, Xi Chen, Chao Wang, Kai Chen, Youqiang Sun, Shiwu Dong, Jiake Xu
Osteoclasts are highly differentiated multinucleated giant cells that play fundamental roles in bone resorption and in the pathogenesis of osteolytic conditions, such as osteoporosis and cancer-induced bone loss. Achyranthes bidentata polysaccharide (ABP) is a hydrophilic compound with anti-oxidation and anti-aging characteristics. The impact of ABP on RANKL-induced osteoclast formation and bone resorption has not been assessed, hence in this study we investigated the effect of ABP on osteoclast formation and resorption in murine bone marrow derived osteoclasts...
January 18, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29344807/inhibition-of-bone-resorption-by-bisphosphonates-interferes-with-orthodontically-induced-midpalatal-suture-expansion-in-mice
#11
Till Koehne, Bärbel Kahl-Nieke, Michael Amling, Heike Korbmacher-Steiner
OBJECTIVES: Craniofacial sutures are important growth sites for skull development and are sensitive to mechanical stress. In order to determine the role of bone resorption in stress-mediated sutural bone growth, midpalatal suture expansion was performed in mice receiving alendronate, an anti-resorptive bisphosphonate. MATERIALS AND METHODS: The midpalatal sutures of 8-week-old C57BL/6 mice were expanded by orthodontic wires over the period of 2 weeks. Mice with maxillary expansion without drug treatment as well as untreated animals served as controls...
January 18, 2018: Clinical Oral Investigations
https://www.readbyqxmd.com/read/29344645/targeted-disruption-of-adenosine-kinase-in-myeloid-monocyte-cells-increases-osteoclastogenesis-and-bone-resorption-in-mice
#12
Qiuying Ye, Ge Li, Shuhua Liu, Yalun Guan, Yunfeng Li, Jinling Li, Huanhuan Jia, Xuejiao Li, Qingnan Li, Ren Huang, Hui Wang, Yu Zhang
Adenosine kinase (ADK) serves an important role in intracellular adenosine clearance via phosphorylating adenosine to AMP. The role of adenosine and its receptors in the maintenance of bone homeostasis is well studied, particularly in osteoclastogenesis and bone resorption; however, the function of ADK in bone metabolism is still unclear. In the present study, utilizing the cre/floxp recombination system, mice with conditional loss of ADK function in myeloid monocyte cells were used to assess the effect of ADK deficiency on bone metabolism...
January 17, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29343249/microrna-124-inhibits-bone-metastasis-of-breast-cancer-by-repressing-interleukin-11
#13
Wei-Luo Cai, Wen-Ding Huang, Bo Li, Tian-Rui Chen, Zhen-Xi Li, Cheng-Long Zhao, Heng-Yu Li, Yan-Mei Wu, Wang-Jun Yan, Jian-Ru Xiao
BACKGROUND: Most patients with breast cancer in advanced stages of the disease suffer from bone metastases which lead to fractures and nerve compression syndromes. microRNA dysregulation is an important event in the metastases of breast cancer to bone. microRNA-124 (miR-124) has been proved to inhibit cancer progression, whereas its effect on bone metastases of breast cancer has not been reported. Therefore, this study aimed to investigate the role and underlying mechanism of miR-124 in bone metastases of breast cancer...
January 17, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29342179/the-polymethoxy-flavonoid-sudachitin-suppresses-inflammatory-bone-destruction-by-directly-inhibiting-osteoclastogenesis-due-to-reduced-ros-production-and-mapk-activation-in-osteoclast-precursors
#14
Yoko Ohyama, Junta Ito, Victor J Kitano, Jun Shimada, Yoshiyuki Hakeda
Inflammatory bone diseases, including rheumatoid arthritis, periodontitis and peri-implantitis, are associated not only with the production of inflammatory cytokines but also with local oxidative status, which is defined by intracellular reactive oxygen species (ROS). Osteoclast differentiation has been reported to be related to increased intracellular ROS levels in osteoclast lineage cells. Sudachitin, which is a polymethoxyflavone derived from Citrus sudachi, possesses antioxidant properties and regulates various functions in mammalian cells...
2018: PloS One
https://www.readbyqxmd.com/read/29339399/ovariectomy-induced-bone-loss-in-tnf%C3%AE-and-il6-knockout-mice-is-regulated-by-different-mechanisms
#15
Siyi Zhu, Hongchen He, Chengfei Gao, Guojing Luo, Ying Xie, Haiming Wang, Li Tian, Chen Xiang, Yu Xijie, Chengqi He
Female wild-type (WT), TNFα knockout (TNFα-/-) or IL6 knockout (IL6-/-) mice aged 12 weeks were sham-operated (SHAM) or subjected to OVX and euthanized after 4 weeks. Bone mass and skeletal microarchitecture were determined using micro-CT. Bone marrow stromal cells (BMSCs) from all three groups were induced to differentiate into osteoblasts or osteoclasts. Bone metabolism was assessed by histological analysis and qRT-PCR. OVX significantly increased the body weight only in WT mice and decreased the uterine weight in all three genotypes...
January 16, 2018: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29339027/a-comparative-study-of-osteopontin-and-mmp-2-protein-expression-in-peripheral-and-central-giant-cell-granuloma-of-the-jaws
#16
Nooshin Mohtasham, Nasrollah Saghravanian, Bahareh Fatemi, Mehdi Vahedi, Monavar Afzal-Aghaee, Hamideh Kadeh
INTRODUCTION: Oral peripheral and central giant cell granulomas are lesions with little-known etiology and pathogenesis. OBJECTIVE: The aim of this study was to compare matrix metalloproteinases-2 and osteopontin protein expression in the multinucleated giant cells and mononuclear cells of the peripheral and central giant cell granuloma lesions. METHODS: In this retrospective study, the presence of matrix metalloproteinases-2 and osteopontin in 37 cases of central giant cell granuloma and 37 cases of peripheral giant cell granuloma paraffin blocks were assessed by streptavidin-biotin immunohistochemistry...
December 27, 2017: Brazilian Journal of Otorhinolaryngology
https://www.readbyqxmd.com/read/29337106/loss-of-tgf-%C3%AE-signaling-in-osteoblasts-increases-basic-fgf-and-promotes-prostate-cancer-bone-metastasis
#17
Xiangqi Meng, Alexandra Vander Ark, Paul Daft, Erica Woodford, Jie Wang, Zachary Madaj, Xiaohong Li
TGF-β plays a central role in prostate cancer (PCa) bone metastasis, and it is crucial to understand the bone cell-specific role of TGF-β signaling in this process. Thus, we used knockout (KO) mouse models having deletion of the Tgfbr2 gene specifically in osteoblasts (Tgfbr2Col1CreERT KO) or in osteoclasts (Tgfbr2LysMCre KO). We found that PCa-induced bone lesion development was promoted in the Tgfbr2Col1CreERT KO mice, but was inhibited in the Tgfbr2LysMCre KO mice, relative to their respective control Tgfbr2FloxE2 littermates...
January 11, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29334656/activated-protein-c-suppresses-osteoclast-differentiation-via-endothelial-protein-c-receptor-protease-activated-receptor-1-sphingosine-1-phosphate-receptor-and-apolipoprotein-e-receptor-2
#18
Kakunoshin Yoshida, Nobuyuki Akita, Takayuki Okamoto, Kunihiro Asanuma, Atsumasa Uchida, Akihiro Sudo, Motomu Shimaoka, Koji Suzuki, Tatsuya Hayashi
INTRODUCTION: Bone remodeling relies on a delicate balance between formation and resorption of bone tissues, processes in which bone-forming osteoblasts and bone-resorbing osteoclasts play central roles. Recently, we reported that anticoagulant activated protein C (APC) promotes osteoblast proliferation, but the role of the blood coagulation system in bone remodeling remains unclear. In this study, to further elucidate the relationship between bone remodeling and blood coagulation, we investigated the effect of APC on osteoclast differentiation...
January 3, 2018: Thrombosis Research
https://www.readbyqxmd.com/read/29334613/reduced-mir-144-3p-expression-in-serum-and-bone-mediates-osteoporosis-pathogenesis-by-targeting-rank
#19
Chunqing Wang, Hanliang He, Yu Jiang, Liang Wang, Youjia Xu
Osteoblasts and osteoclasts are responsible for the formation and resorption of bone, respectively. An imbalance between these two processes results in a disease called osteoporosis, in which a decreased level of bone strength increases the risk of a bone fracture. MicroRNAs (miRNAs) are small non-coding RNA molecules of 18-25 nucleotides that have been previously shown to control bone metabolism by regulating osteoblast and osteoclast differentiation. In the present study, we detected the expression pattern of 10 miRNAs in patient serum samples, and identified six miRNAs altered expression in patients with osteoporosis relative to non-osteoporosis...
January 15, 2018: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/29333009/peripheral-and-central-giant-cell-lesions-in-children-institutional-experience-at-subharti-dental-college-and-hospital
#20
Preetika Chandna, Nikhil Srivastava, Vishal Bansal, Vijay Wadhwan, Prajesh Dubey
Introduction: Giant cell lesions (GCG) are a group of varied lesions that contain a multitude of multinucleated, osteoclast like giant cells within connective tissue stroma. These include giant cell granulomas which may be central (CGCG), if they lie within the jaw bone, or, peripheral (PGCG) if they lie within the soft tissue. Giant cell granulomas comprised 9.29% of all oral lesions. This case series comprises of 5 giant cell lesions in children between the ages of 4 to 12 years. Materials and Methods: A retrospective analysis was conducted of all patients who were diagnosed with giant cell lesions and treated over a period of 10 years (from August 2004 to August 2014) at Subharti Dental College and Hospital, Meerut, India...
October 2017: Indian Journal of Medical and Paediatric Oncology
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