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https://www.readbyqxmd.com/read/28651365/cathepsin-k-inhibitors-for-osteoporosis-biology-potential-clinical-utility-and-lessons-learned
#1
Matthew T Drake, Bart L Clarke, Merry Jo Oursler, Sundeep Khosla
Cathepsin K is a cysteine protease member of the cathepsin lysosomal protease family. While cathepsin K is highly expressed in osteoclasts, lower levels of cathepsin K are also found in a variety of other tissues. Secretion of cathepsin K from the osteoclast into the sealed osteoclast-bone cell interface results in efficient degradation of type I collagen. The absence of cathepsin K activity in humans results in pycnodysostosis, characterized by increased bone mineral density and fractures. Pharmacological cathepsin K inhibition leads to continuous increases in BMD for up to five years of treatment and improves bone strength at the spine and hip...
June 23, 2017: Endocrine Reviews
https://www.readbyqxmd.com/read/28651235/alpinumisoflavone-inhibits-osteoclast-differentiation-and-exerts-anti-osteoporotic-effect-in-ovariectomized-mice
#2
Wei Cong, Chao Zhou, Jun Yin
Alpinumisoflavone (AIF), a naturally occurring flavonoid compound exacted from Derris eriocarpa, has been found to have a number of pharmacological activities. However, its role in bone disorder has not been investigated. The aim of this study is to evaluate the osteoprotective effect of AIF on ovariectomy-induced bone loss in mice model and related underlying mechanisms. Our study provides experimental evidence that AIF could regulate the remodeling process of bone and exert osteoprotective effect against ovariectomy-induced bone loss...
June 23, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28650106/dok3-modulates-bone-remodeling-by-negatively-regulating-osteoclastogenesis-and-positively-regulating-osteoblastogenesis
#3
Xiaofeng Cai, Junjie Xing, Courtney L Long, Qisheng Peng, Mary Beth Humphrey
Osteoclastogenesis is essential for bone remodeling and normal skeletal maintenance. RANKL promotes osteoclast differentiation and function but requires costimulation of immunoreceptor tyrosine-based activation motif (ITAM)-coupled immunoreceptors. Triggering receptor expressed on myeloid cells-2 (TREM2) coupled to ITAM-adaptor protein DNAX activation protein 12kDA (DAP12) provides costimulation of intracellular calcium signaling during osteoclastogenesis. Previously, we found that downstream of kinase-3 (DOK3) physically associates with DAP12 to inhibit toll-like receptor (TLR)-induced inflammatory signaling in macrophages...
June 26, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28648703/osteoclasts-in-periprosthetic-osteolysis-the-charnley-arthroplasty-revisited
#4
Sebastian S Mukka, Göran N Andersson, Kjell R Hultenby, Olof G Sköldenberg, Joakim P Nordahl, Thomas M Eisler
BACKGROUND: Periprosthetic osteolysis by polyethylene wear debris-triggered osteoclasts is viewed as the main pathophysiological pathway in aseptic loosening in total hip arthroplasty. The present aim was to study osteoclast occurrence in osteolytic lesions in early and late revisions of the Charnley low-friction torque arthroplasty (CLFA). METHODS: Biopsies of the soft interface membrane and the adjacent bone were taken from osteolytic lesions during revision of 16 loose CLFA, early (2-6 years) or late (>10 years) after primary surgery...
May 22, 2017: Journal of Arthroplasty
https://www.readbyqxmd.com/read/28647887/connexins-and-pannexins-in-bone-and-skeletal-muscle
#5
REVIEW
Lilian I Plotkin, Hannah M Davis, Bruno A Cisterna, Juan C Sáez
PURPOSE OF REVIEW: To discuss current knowledge on the role of connexins and pannexins in the musculoskeletal system. RECENT FINDINGS: Connexins and pannexins are crucial for the development and maintenance of both bone and skeletal muscle. In bone, the presence of connexin and more recently of pannexin channels in osteoblasts, osteoclasts, and osteocytes has been described and shown to be essential for normal skeletal development and bone adaptation. In skeletal muscles, connexins and pannexins play important roles during development and regeneration through coordinated regulation of metabolic functions via cell-to-cell communication...
June 24, 2017: Current Osteoporosis Reports
https://www.readbyqxmd.com/read/28647885/osteomacs-and-bone-regeneration
#6
REVIEW
Lena Batoon, Susan Marie Millard, Liza Jane Raggatt, Allison Robyn Pettit
PURPOSE OF REVIEW: Mounting evidence supporting the critical contribution of macrophages, in particular osteal macrophages, to bone regeneration is reviewed. We specifically examine the potential role of macrophages in the basic multicellular units coordinating lifelong bone regeneration via remodelling and bone regeneration in response to injury. We review and discuss the distinctions between macrophage and osteoclast contributions to bone homeostasis, particularly the dichotomous role of the colony-stimulating factor 1-colony-stimulating factor 1 receptor axis...
June 24, 2017: Current Osteoporosis Reports
https://www.readbyqxmd.com/read/28647591/chitosan-based-nanocomposites-for-the-repair-of-bone-defects
#7
L Keller, A Regiel-Futyra, M Gimeno, S Eap, G Mendoza, V Andreu, Q Wagner, A Kyzioł, V Sebastian, G Stochel, M Arruebo, N Benkirane-Jessel
Chitosan scaffolds of different deacetylation degrees, average molecular weights and concentrations reinforced with silica nanoparticles were prepared for bone tissue regeneration. The resulting nanocomposites showed similar pore sizes (<300 μm) regardless the deacetylation degree and concentration used in their formulation. Their mechanical compression resistance was increased by a 30% with the addition of silica nanoparticles as nanofillers. The biocompatibility of the three-dimensional chitosan scaffolds was confirmed by the Alamar Blue assay in human primary osteoblasts as well as the formation of cell spheroids indicative of their great potential for bone regeneration...
June 22, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28647392/a-novel-dual-inhibitor-of-microtubule-and-bruton-s-tyrosine-kinase-inhibits-survival-of-multiple-myeloma-and-osteoclastogenesis
#8
Manoj K Pandey, Krishne Gowda, Shen-Shu Sung, Thomas Abraham, Tulin Budak-Alpdogan, Giampolo Talamo, Sinisa Dovat, Shantu Amin
Bruton's tyrosine kinase (BTK) regulates many vital signaling pathways and play critical role in cell proliferation, survival, migration, and resistance. Earlier we reported that a small molecule KS99 is an inhibitor of tubulin polymerization. In the present study we explored that whether KS99 is a dual inhibitor of BTK and tubulin polymerization. While it is known that BTK is required for clonogenic growth, and resistance; and microtubules are essential for cancer cell growth; dual targeting of these two components has not been explored...
June 21, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28647374/overexpression-of-dentin-matrix-protein-1-in-nestin-cells-causes-bone-loss-in-mouse-long-bone
#9
Min Pan, Yuteng Weng, Yao Sun
The well-known matrix protein Dentin matrix protein 1 (DMP1) is expressed by osteoblasts and osteocytes in bone, and it controls bone mineralization. Recently, it has been found that DMP1 is also expressed in other cell types, such as chondrocytes. Nestin(+) cells are one important type of progenitor cell in bone marrow and are associated with bone remodeling. In our preliminary experiment, DMP1 could also be detected in Nestin(+) cells in bone marrow. This study was designed to explore the effect on bone of DMP1 in Nestin(+) cells...
June 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28647227/in-vivo-cellular-reactions-to-different-biomaterials-physiological-and-pathological-aspects-and-their-consequences
#10
REVIEW
Sarah Al-Maawi, Anna Orlowska, Robert Sader, C James Kirkpatrick, Shahram Ghanaati
Biomaterials are widely used in guided bone regeneration (GBR) and guided tissue regeneration (GTR). After application, there is an interaction between the host immune system and the implanted biomaterial, leading to a biomaterial-specific cellular reaction. The present review focuses on cellular reactions to numerous biomaterials in vivo with consideration of different implantation models and microenvironments in different species, such as subcutaneous implantation in mice and rats, a muscle model in goats and a femur model in rabbits...
June 21, 2017: Seminars in Immunology
https://www.readbyqxmd.com/read/28643925/a-new-cyte-in-orthodontics-osteocytes-in-tooth-movement
#11
REVIEW
E E Bumann, S A Frazier-Bowers
Orthodontic tooth movement (OTM) relies on the orchestration of clinical and biologic events that include the application of clinical force followed by a cascade of cellular and molecular responses. Our understanding about OTM today has evolved from, and is largely based on historic studies. However, the advances in bone biology and clinical orthodontics today continue to pave the pathway towards an improved knowledge base, and state of the art therapeutics in OTM. Osteoblasts and osteoclasts have been the primary cells analyzed in OTM...
June 2017: Orthodontics & Craniofacial Research
https://www.readbyqxmd.com/read/28643924/exosomes-novel-regulators-of-bone-remodelling-and-potential-therapeutic-agents-for-orthodontics
#12
REVIEW
L S Holliday, K P McHugh, J Zuo, J I Aguirre, J K Neubert, W J Rody
Recent studies suggest that exosomes are involved in intercellular communication required for the maintenance of healthy bone. Exosomes are small (30-150 nm in diameter) extracellular vesicles that are formed in multivesicular bodies and are released from cells as the multivesicular bodies fuse with the plasma membrane. Regulatory exosomes have the capacity to exert profound control over target cells. They can stimulate plasma membrane receptors and are also internalized by the target cell delivering proteins, lipids, small molecules and functional RNAs from the cell of origin...
June 2017: Orthodontics & Craniofacial Research
https://www.readbyqxmd.com/read/28643914/the-use-of-cell-culture-platforms-to-identify-novel-markers-of-bone-and-dentin-resorption
#13
W J Rody, O Krokhin, V Spicer, C A Chamberlain, M Chamberlain, K P McHugh, S M Wallet, A K Emory, J D Crull, L S Holliday
OBJECTIVES: 1) To test the hypothesis that there would be proteomic differences in the composition of exosomes isolated from osteoclasts and odontoclasts and 2) to determine the clinical usefulness of these in vitro biomarker candidates. MATERIALS AND METHODS: Mouse bone marrow-derived precursors were cultured on either dentin or bone slices and allowed to mature and begin resorption. Exosomes were isolated from cell culture media and characterized by mass spectrometry...
June 2017: Orthodontics & Craniofacial Research
https://www.readbyqxmd.com/read/28638666/osteoma-cutis-of-the-face-in-cbct-images
#14
Daniah Alhazmi, Fatma Badr, Fatima Jadu, Ahmed M Jan, Zainab Abdulsalam
Osteoma cutis (OC) is a rare benign disorder where osseous nodules form in the reticular layer of normal skin. These nodules are formed by the deposition of lamellar bone and are characterized by osteocytes in the core and osteoclasts around the periphery. Interpretation of osteoma cutis cases has always been challenging especially using conventional two-dimensional (2D) radiographs, owing to difficulty in localization. Cone beam CT (CBCT), with its three-dimensional (3D) capabilities, offers a great tool to help detect and diagnose these calcific entities...
2017: Case Reports in Dentistry
https://www.readbyqxmd.com/read/28637990/effect-of-the-leukotriene-receptor-antagonist-montelukast-on-orthodontic-tooth-movement
#15
Hossam Asaad, Rabab Al-Sabbagh, Darem Al-Tabba, Omar Kujan
Asthma is a chronic inflammatory disease, and its prevalence is relatively high among children. Optimal management of asthma often requires long-term pharmacotherapy; however, the effects of these medications on orthodontic treatment is uncertain. We evaluated the effects of the leukotriene LTD4 receptor antagonist montelukast on orthodontic tooth movement in an animal model. Eight mongrel dogs were given montelukast for periods up to 4 weeks. An orthodontic force of 150-200 g was applied to move the second and fourth premolars toward the site of the extracted third premolar...
2017: Journal of Oral Science
https://www.readbyqxmd.com/read/28637984/anti-inflammatory-effect-of-rosuvastatin-decreases-alveolar-bone-loss-in-experimental-periodontitis
#16
Fatma Y Kırzıoğlu, Memduha Tözüm Bulut, Burak Doğan, Özlem Fentoğlu, Özlem Özmen, Süleyman A Çarsancaklı, Ayşe G Ergün, Muhsin Özdem, Hikmet Orhan
The effects of systemically administered rosuvastatin on alveolar bone loss (ABL), cytokine levels and oxidative status were investigated in rats with ligature-induced periodontitis. Rats were divided randomly into four groups: a non-ligated group (C); a non-ligated+rosuvastatin group (R); a ligated group (P); and a ligated+rosuvastatin group (PR). Ligatures were placed at the maxillary second molars, and rosuvastatin was administered for 14 days. After the rats had been euthanatized, histomorphometric and histological analyses were performed, and the serum levels of interleukin (IL)-1β, IL-10 and oxidant and antioxidant parameters (malondialdehyde [MDA], superoxide dismutase, glutathione, and glutathione peroxidase) were evaluted by enzyme-linked immunosorbent assay...
2017: Journal of Oral Science
https://www.readbyqxmd.com/read/28637021/dectin-1-signaling-inhibits-osteoclastogenesis-via-il-33-induced-inhibition-of-nfatc1
#17
Xiaoqing Zhu, Yinghua Zhao, Yuxue Jiang, Tianxue Qin, Jintong Chen, Xiao Chu, Qing Yi, Sujun Gao, Siqing Wang
Abnormal osteoclast activation contributes to osteolytic bone diseases (OBDs). It was reported that curdlan, an agonist of dectin-1, inhibits osteoclastogenesis. However, the underlying mechanisms are not fully elucidated. In this study, we found that curdlan potently inhibited RANKL-induced osteoclast differentiation and the resultant bone resorption. Curdlan inhibited the expression of nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), the key transcriptional factor for osteoclastogenesis. Notably, dectin-1 activation increased the expression of MafB, an inhibitor of NFATc1, and IL-33 in osteoclast precursors...
June 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636229/recovery-from-reproductive-and-morphological-abnormalities-in-medaka-oryzias-latipes-following-a-14-day-exposure-to-diclofenac
#18
Hirofumi Yokota, Kaho Higashi, Erina Hanada, Ei Matsuzaki, Yukinari Tsuruda, Tomoko Suzuki, Eiko Nakano, Sayaka Eguchi
Mating pairs of medaka (Oryzias latipes) were exposed to diclofenac (DCF) at measured concentrations of 0 (control), 7.1, 37, and 78 µg/L for 14 d under static-renewal conditions. Effects on reproductive success, as well as morphological abnormalities, of the fish were assessed. During the exposure period, both fecundity and fertility were significantly decreased in the 37 and 78 µg/L treatments groups, and swollen abdomens in females were observed in all exposure groups. Notably, a defect of the lower jaw also was observed in four male fish: two at 37 µg/L, and the others at 78 µg/L of DCF...
June 21, 2017: Environmental Toxicology and Chemistry
https://www.readbyqxmd.com/read/28635959/optogenetic-activation-of-plexin-b1-reveals-contact-repulsion-between-osteoclasts-and-osteoblasts
#19
Abhijit Deb Roy, Taofei Yin, Shilpa Choudhary, Vladimir Rodionov, Carol C Pilbeam, Yi I Wu
During bone remodelling, osteoclasts induce chemotaxis of osteoblasts and yet maintain spatial segregation. We show that osteoclasts express the repulsive guidance factor Semaphorin 4D and induce contact inhibition of locomotion (CIL) in osteoblasts through its receptor Plexin-B1. To examine causality and elucidate how localized Plexin-B1 stimulation may spatiotemporally coordinate its downstream targets in guiding cell migration, we develop an optogenetic tool for Plexin-B1 designated optoPlexin. Precise optoPlexin activation at the leading edge of migrating osteoblasts readily induces local retraction and, unexpectedly, distal protrusions to steer cells away...
June 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28631442/osteoblast-migration-in-vertebrate-bone
#20
Antonia Thiel, Marie K Reumann, Adele Boskey, Johannes Wischmann, Rüdiger von Eisenhart-Rothe, Philipp Mayer-Kuckuk
Bone formation, for example during bone remodelling or fracture repair, requires mature osteoblasts to deposit bone with remarkable spatial precision. As osteoblast precursors derive either from circulation or resident stem cell pools, they and their progeny are required to migrate within the three-dimensional bone space and to navigate to their destination, i.e. to the site of bone formation. An understanding of this process is emerging based on in vitro and in vivo studies of several vertebrate species. Receptors on the osteoblast surface mediate cell adhesion and polarization, which induces osteoblast migration...
June 19, 2017: Biological Reviews of the Cambridge Philosophical Society
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