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Pakchisa Khonsuphap, Prasit Pavasant, Rizky Aditya Irwandi, Chidchanok Leethanakul, Anjalee Vacharaksa
BACKGROUND: Prostaglandin E2 (PGE2) accumulates in inflamed periodontal tissue and induces the receptor activator of nuclear factor kappa-B ligand (RANKL)-RANK-osteoprotegerin (OPG) signaling associated with bone resorption. Although oral epithelial cells maintain tissue homeostasis, the role of these cells in RANKL regulation remains unknown. METHODS: To mimic inflamed condition, RANKL upregulation in human mandibular osteoblast-like cells (HMOBs) were stimulated with PGE2...
October 20, 2016: Journal of Periodontology
Penelope D Ottewell
The primary role of osteoblasts is to lay down new bone during skeletal development and remodelling. Throughout this process osteoblasts directly interact with other cell types within bone, including osteocytes and haematopoietic stem cells. Osteoblastic cells also signal indirectly to bone-resorbing osteoclasts via the secretion of RANKL. Through these mechanisms, cells of the osteoblast lineage help retain the homeostatic balance between bone formation and bone resorption. When tumour cells disseminate in the bone microenvironment, they hijack these mechanisms, homing to osteoblasts and disrupting bone homeostasis...
September 2016: Journal of Bone Oncology
Raphael Leblanc, Olivier Peyruchaud
Blood platelets have been known for more than a century as important partners for successful metastatic dissemination of solid tumors. Cancer cell-induced platelet activation is a key event responsible for prometastatic activity of platelets. Blocking platelet aggregation inhibits the progression of skeletal metastases through mechanisms that are not fully understood. The establishment and progression of bone metastases are strongly influenced by the bone remodeling process. Growth factors and cytokines released upon platelet activation may contribute to both skeletal tumor growth and osteolytic lesions...
September 2016: Journal of Bone Oncology
François Le Pape, Geoffrey Vargas, Philippe Clézardin
Breast cancer frequently metastasises to the skeleton, interfering with the normal bone remodelling process and inducing bone degradation. Bone degradation is caused by osteoclasts, the normal bone-resorbing cells. Osteoclast-mediated bone degradation subsequently leads to the release of bone-derived factors that promote skeletal tumour growth. Osteoclasts themselves stimulate tumour growth. This Review describes the molecular mechanisms through which osteoclasts and breast cancer cells collaborate with each other, triggering the formation of osteolytic bone metastasis...
September 2016: Journal of Bone Oncology
Martin Sztacho, Sandra Segeletz, Maria Arantzazu Sanchez-Fernandez, Cornelia Czupalla, Christian Niehage, Bernard Hoflack
Bone resorption in vertebrates relies on the ability of osteoclasts to assemble F-actin-rich podosomes that condense into podosomal belts, forming sealing zones. Sealing zones segregate bone-facing ruffled membranes from other membrane domains, and disassemble when osteoclasts migrate to new areas. How podosome/sealing zone dynamics is regulated remains unknown. We illustrate the essential role of the membrane scaffolding F-BAR-Proline-Serine-Threonine Phosphatase Interacting Proteins (PSTPIP) 1 and 2 in this process...
2016: PloS One
Emeline Puissant, Marielle Boonen
Osteoclasts are giant bone-resorbing cells originating from monocytes/macrophages. During their differentiation, they overexpress two lysosomal enzymes, cathepsin K and TRAP, which are secreted into the resorption lacuna, an acidified sealed area in contact with bone matrix where bone degradation takes place. Here we report that the acid hydrolase HYAL1, a hyaluronidase able to degrade the glycosaminoglycans hyaluronic acid (HA) and chondroitin sulfate, is also upregulated upon osteoclastogenesis. The mRNA expression and protein level of HYAL1 are markedly increased in osteoclasts differentiated from RAW264...
2016: PloS One
Bryant R England, Geoffrey M Thiele, Ted R Mikuls
PURPOSE OF REVIEW: This article reviews recent literature on the origin and pathogenic role of anticitrullinated protein antibodies (ACPAs) in rheumatoid arthritis (RA). RECENT FINDINGS: ACPAs and ACPA-immune complexes interact with immune cells to facilitate articular inflammation. Findings from recent in vitro and in vivo studies are congruent with epidemiologic observations in RA supporting a pathogenic role of ACPAs. SUMMARY: ACPAs target proteins/peptides with citrullinated epitopes and serve as informative RA biomarkers...
October 13, 2016: Current Opinion in Rheumatology
So-Jeong Lee, Eun-Hye Lee, Seung-Yoon Park, Jung-Eun Kim
Osteoporosis is the most common age-related bone disease that is characterized by an imbalance between osteoblasts for bone formation and osteoclasts for bone resorption. Anti-catabolic drugs have been developed to inhibit osteoclast activity and to prevent bone loss in osteoporosis. However, because it is difficult to increase bone mass in osteoporotic bone, it would be beneficial to simultaneously enhance osteoblast function and thus form bone. Osterix (Osx) is an essential transcription factor for osteoblast differentiation...
October 14, 2016: Gene
Kai Hu, Bjorn R Olsen
Vascular Endothelial Growth factor A (VEGF) is a critical regulator of vascular development, postnatal angiogenesis and homeostasis, and it is essential for bone development and repair. Blood vessels serve both as structural templates for bone formation and they provide essential cells, growth factors and minerals needed for synthesis and mineralization, as well as turnover, of the extracellular matrix in bone. Through its regulation of angiogenesis, VEGF contributes to coupling of osteogenesis to angiogenesis, and it directly controls the differentiation and function of osteoblasts and osteoclasts...
October 17, 2016: Developmental Dynamics: An Official Publication of the American Association of Anatomists
Anne Blangy
Tensins are focal adhesion molecules that were identified and characterized in the late 1980's - early 1990's. They play an essential role in the control of cell adhesion. Tensins can bind the tail of ß integrin via their Phospho Tyrosine Binding (PTB) domain, they exhibit various protein interaction domains including a Src Homology 2 (SH2) domain and they are serine-, threonine- and tyrosine-phosphorylated in response to various stimuli. Tensins serve as scaffolds to gather signaling molecules at the extracellular matrix adhesion complexes...
October 17, 2016: Biology of the Cell
Dan Xu, Ying Lyu, Xiaowen Chen, Xiaoyu Zhu, Jinqiu Feng, Yajun Xu
Fructus ligustri Lucidi (FLL) is the fruit of Ligustrum lucidum Ait and a traditional Chinese medicine, primarily known for its role in osteoporosis prevention and treatment. The present study aimed to elucidate the effect and underlying mechanism of action of ethanol extract of FLL on osteoclast differentiation and bone resorption, and to identify the active compounds within it. RAW264.7 murine monocyte/macrophage cells were stimulated with the receptor activator of nuclear factor κB ligand (RANKL) to induce osteoclast differentiation in vitro...
October 13, 2016: Molecular Medicine Reports
Hai Li, Dahang Zhao, Shengjing Wang, Jing Ding, Li Zhao
It has been confirmed that bone morphogenetic protein-9 (BMP-9) promotes the differentiation of osteoblasts. However, the ways in which BMP‑9 exerts its effects on the differentiation of osteoclasts and bone resorption remain to be elucidated. The present study was designed to investigate the roles and the molecular mechanism of BMP‑9 on the proliferation and differentiation of osteoclast precursors in vitro. Mouse spleen macrophages (RAW 264.7 cells) were cultured in the presence of receptor activator for nuclear factor‑κb ligand (RANKL) in vitro...
October 5, 2016: Molecular Medicine Reports
Monica Montesi, Katharina Jähn, Lynda Bonewald, Susanna Stea, Barbara Bordini, Alina Beraudi
Skeletal unloading leads to hypoxia in the bone microenvironment, resulting in imbalanced bone remodeling that favors bone resorption. Osteocytes, the mechanosensors of bone, have been demonstrated to orchestrate bone homeostasis. Hypoxic osteocytes either undergo apoptosis or actively stimulate osteoclasts to remove bone matrix during hypoxia. Oxygen‑regulated protein 150 (ORP150) is an endoplasmic reticulum‑associated chaperone that has been observed to serve an important role in the cellular adaptation to hypoxia and in preventing cellular apoptosis in various tissue types...
September 26, 2016: Molecular Medicine Reports
Masaaki Ikeda, Yoshitaka Yoshimura, Takashi Kikuiri, Mino Matsuno, Tomokazu Hasegawa, Kumu Fukushima, Takako Hayakawa, Hajime Minamikawa, Kuniaki Suzuki, Junichiro Iida
Bone remodeling is an important factor in orthodontic tooth movement. During orthodontic treatment, osteoclasts are subjected to various mechanical stimuli, and this promotes or inhibits osteoclast differentiation and fusion. It has been previously reported that the release from tensile force induces osteoclast differentiation. However, little is known about how release from compressive force affects osteoclasts. The present study investigated the effects of release from compressive force on osteoclasts. The number of tartrate‑resistant acid phosphatase (TRAP)‑positive multinucleated osteoclasts derived from RAW264...
October 5, 2016: Molecular Medicine Reports
Silvia Panzavolta, Paola Torricelli, Sonia Casolari, Annapaola Parrilli, Sofia Amadori, Milena Fini, Adriana Bigi
The systemic administration of bisphosphonates (BPs) for the treatment of metabolic diseases characterized by abnormal bone loss suffers from several adverse side effects, which can be reduced by implementation of alternative modes of administration. In this work, glutaraldehyde cross-linked gelatin scaffolds are proposed as delivery systems of calcium alendronate monohydrate (CaAL•H2 O). The 3D highly porous scaffolds display a relevant interconnected porosity (>94%), independently from CaAL•H2 O content (0, 3, and 6 wt%)...
October 17, 2016: Macromolecular Bioscience
Aurore Varela, Luc Chouinard, Elisabeth Lesage, Susan Y Smith, Gary Hattersley
Abaloparatide is a novel 34-amino acid peptide selected to be a potent and selective activator of the parathyroid hormone receptor (PTH1R) signaling pathway with 41% homology to PTH(1-34) and 76% homology to PTHrP(1-34). A 12-month treatment study was conducted in osteopenic ovariectomized (OVX) rats to characterize the mechanisms by which abaloparatide increases bone mass. Sprague-Dawley (SD) rats were subjected to OVX or sham surgery at age 6 months and left untreated for 3 months to allow OVX-induced bone loss...
October 17, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
Bipradas Roy, Mary E Curtis, Letimicia S Fears, Samuel N Nahashon, Hugh M Fentress
Obesity and osteoporosis are two alarming health disorders prominent among middle and old age populations, and the numbers of those affected by these two disorders are increasing. It is estimated that more than 600 million adults are obese and over 200 million people have osteoporosis worldwide. Interestingly, both of these abnormalities share some common features including a genetic predisposition, and a common origin: bone marrow mesenchymal stromal cells. Obesity is characterized by the expression of leptin, adiponectin, interleukin 6 (IL-6), interleukin 10 (IL-10), monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), macrophage colony stimulating factor (M-CSF), growth hormone (GH), parathyroid hormone (PTH), angiotensin II (Ang II), 5-hydroxy-tryptamine (5-HT), Advance glycation end products (AGE), and myostatin, which exert their effects by modulating the signaling pathways within bone and muscle...
2016: Frontiers in Physiology
Imranul Alam, Amie K McQueen, Dena Acton, Austin M Reilly, Rita L Gerard-O'Riley, Dana K Oakes, Charishma Kasipathi, Abigail Huffer, Weston B Wright, Michael J Econs
Autosomal dominant osteopetrosis type II (ADO2) is a heritable osteosclerotic bone disorder due to dysfunctional osteoclast activity. ADO2 is caused by missense mutations in the chloride channel 7 (CLCN7) gene characterized by osteosclerosis with multiple fractures. ADO2 can result in osteomyelitis, visual loss and bone marrow failure. Currently, there is no cure for ADO2, and until recently no appropriate animal model of ADO2 existed to understand better the pathogenesis of this disease and to test new therapies...
October 14, 2016: Bone
Koichi Ichikawa, Yoichi Ohta, Kenji Mamoto, Shigekazu Mizokawa, Yukihide Minoda, Yuuki Imai, Kunio Takaoka, Hiroaki Nakamura
Bone Morphogenetic Proteins (BMPs) strongly induce the recruitment and differentiation of mesenchymal progenitor cells into mature osteoblasts, but also directly and indirectly stimulate differentiation of osteoclast progenitor cells and acceleration of mature osteoclasts function leading excessive bone resorption. Bisphosphonates, such as zoledronate (ZOL), inhibit osteoclasts function and osteoclasts mediated bone resorption. The short or middle term effect of BMPs and bisphosphonates on bone formation were previously reported, but there was no study that argue about the long term effect of bisphosphonates on BMP-induced bone anabolism...
October 13, 2016: Biochemical and Biophysical Research Communications
Hwan D Kim, Hae Lin Jang, Hyo-Yong Ahn, Hye Kyoung Lee, Jungha Park, Eun-Seo Lee, Eunjee A Lee, Yong-Hoon Jeong, Do-Gyoon Kim, Ki Tae Nam, Nathaniel S Hwang
Bone remodeling process relies on complex signaling pathway between osteoblasts and osteoclasts and control mechanisms to achieve homeostasis of their growth and differentiation. Despite previous achievements in understanding complicated signaling pathways between cells and bone extracellular matrices during bone remodeling process, a role of local ionic concentration remains to be elucidated. Here, we demonstrate that synthetic whitlockite (WH: Ca18Mg2(HPO4)2(PO4)12) nanoparticles can recapitulate early-stage of bone regeneration through stimulating osteogenic differentiation, prohibiting osteoclastic activity, and transforming into mechanically enhanced hydroxyapatite (HAP)-neo bone tissues by continuous supply of PO4(3-) and Mg(2+) under physiological conditions...
October 11, 2016: Biomaterials
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