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Anti sclerostin antibodies

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https://www.readbyqxmd.com/read/29653294/sclerostin-vaccination-mitigates-estrogen-deficiency-induction-of-bone-mass-loss-and-microstructure-deterioration
#1
Feng-Sheng Wang, Re-Wen Wu, Wei-Shiung Lain, Tsai-Chen Tsai, Yu-Shan Chen, Yi-Chih Sun, Huei-Jing Ke, Jui-Chen Li, Jau-Lang Hwang, Jih-Yang Ko
Sclerostin (SOST) is a Wnt signaling inhibitor detrimental to osteogenic differentiation and bone mineral acquisition. While control of SOST action delays the pathogenesis of skeletal disorders, the effects of SOST vaccination on the estrogen deficiency-induced bone deterioration remain elusive. In this study, we generated a SOST-Fc fusion protein which was composed of a SOST peptide Pro-Asn-Ala-Ile-Gly along with an IgG Fc fragment. SOST-Fc vaccination increased serum anti-SOST antibody levels and reduced serum SOST concentrations in mice...
April 10, 2018: Bone
https://www.readbyqxmd.com/read/29589203/anabolic-therapy-for-the-treatment-of-osteoporosis-in-childhood
#2
REVIEW
Leanne M Ward, Frank Rauch
PURPOSE OF REVIEW: Numerous forms of osteoporosis in childhood are characterized by low bone turnover (for example, osteoporosis due to neuromuscular disorders and glucocorticoid exposure). Anti-resorptive therapy, traditionally used to treat osteoporosis in the young, is associated with further reductions in bone turnover, raising concerns about the long-term safety and efficacy of such therapy. These observations have led to increasing interest in the role of anabolic therapy to treat pediatric osteoporosis...
March 27, 2018: Current Osteoporosis Reports
https://www.readbyqxmd.com/read/29522281/treatment-with-anti-sclerostin-antibody-to-stimulate-mandibular-bone-formation
#3
Matthew Tamplen, Tristan Fowler, Jeffery Markey, P Daniel Knott, Larry J Suva, Tamara Alliston
BACKGROUND: Anti-Sclerostin antibody (Scl-Ab) is a promising new bone anabolic therapy. Although anti-Scl-Ab stimulates bone formation and repair in the appendicular and axial skeleton, its efficacy in the craniofacial skeleton is still poorly understood. METHODS: Using an established model of Down syndrome-dependent bone deficiency, 10 Ts65Dn mice and 10 wild-type mice were treated weekly via i.v. tail vein injection with vehicle or anti-Sclerostin for 3 weeks and euthanized 1 week after...
March 9, 2018: Head & Neck
https://www.readbyqxmd.com/read/29512530/-homeostasis-and-disorder-of-musculoskeletal-system-diagnosis-and-treatment-of-congenital-musculoskeletal-diseases
#4
Toshimi Michigami
Congenital skeletal dysplasias have been considered to be fundamentally untreatable diseases. However, molecular diagnosis by genetic testing has become more prevalent, and efforts are being made to develop novel therapies based on the pathogenesis. As treatments for osteogenesis imperfecta, in addition to anti-resorptive agents, neutralizing antibodies against sclerostin and transforming growth factor(TGF)-β and chemical chaperones can be beneficial. Enzyme replacement therapy using bone-targeting recombinant alkaline phosphatase has been recently developed to treat hypophosphatasia and has much improved the prognosis of the patients affected with severe forms of the disease...
2018: Clinical Calcium
https://www.readbyqxmd.com/read/29476877/targeted-inhibition-of-sclerostin-for-post-menopausal-osteoporosis-therapy-a-critical-assessment-of-the-mechanism-of-action
#5
REVIEW
Sharmistha Bhattacharyya, Subhashis Pal, Naibedya Chattopadhyay
Promising news in the treatment of osteoporosis is that sequestering sclerostin from circulation with antibodies stimulates robust bone formation. Pre-clinical studies on rodents and monkeys have confirmed that treatment with anti-sclerostin monoclonal antibody (Scl-Ab) increases bone mass improves bone strength and enhances fracture repair. Clinical trials show that bone gain (anabolic effect) is transient and are primarily at central (spine and hips) than peripheral (wrist) sites. Interestingly Scl-Ab also inhibited bone resorption...
February 21, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29470611/osteoporosis-in-rheumatic-diseases-anti-rheumatic-drugs-and-the-skeleton
#6
REVIEW
Alanna M Dubrovsky, Mie Jin Lim, Nancy E Lane
Osteoporosis in rheumatic diseases is a very well-known complication. Systemic inflammation results in both generalized and localized bone loss and erosions. Recently, increased knowledge of inflammatory process in rheumatic diseases has resulted in the development of potent inhibitors of the cytokines, the biologic DMARDs. These treatments reduce systemic inflammation and have some effect on the generalized and localized bone loss. Progression of bone erosion was slowed by TNF, IL-6 and IL-1 inhibitors, a JAK inhibitor, a CTLA4 agonist, and rituximab...
February 22, 2018: Calcified Tissue International
https://www.readbyqxmd.com/read/29419466/sclerostin-and-antisclerostin-antibody-serum-levels-predict-the-presence-of-axial-spondyloarthritis-in-patients-with-inflammatory-bowel-disease
#7
Michele Maria Luchetti, Francesco Ciccia, Chiara Avellini, Devis Benfaremo, Giuliana Guggino, Alessia Farinelli, Monia Ciferri, Matteo Rossini, Silvia Svegliati, Tatiana Spadoni, Laura Bolognini, Giammarco Fava, Piergiorgio Mosca, Rosaria Gesuita, Edlira Skrami, Giovanni Triolo, Armando Gabrielli
OBJECTIVE: The early diagnosis of inflammatory bowel disease (IBD)-associated spondyloarthritis (SpA/IBD) in patients affected by IBD represents a major topic in clinical practice; in particular, to date there are no available serum biomarkers revealing the presence of joint inflammation in these patients. Sclerostin (SOST), an antagonist of the Wnt/β-catenin pathway, and antisclerostin-immunoglobulin G (anti-SOST-IgG) have been recently studied in patients with ankylosing spondylitis (AS) as a putative marker of disease activity...
February 1, 2018: Journal of Rheumatology
https://www.readbyqxmd.com/read/29412118/antibody-administration-for-bone-tissue-engineering-a-systematic-review
#8
Sepanta Hosseinpour, Maryam Rezai Rad, Arash Khojasteh, Homa Zadeh
BACKGROUND: Currently, antibodies are progressively applied in medicine for different purposes from diagnosis to treatments. Over twenty monoclonal antibodies utilized for many therapeutic reasons from therapy of cancers, immune disorders, and osteoporosis to localized bony defects. In addition, therapeutic antibodies represented various findings in bone tissue engineering. OBJECTIVES: The current study aims to systematically review the available literature on antibody assisted bone regeneration in animal models...
February 6, 2018: Current Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29344330/developments-in-rare-bone-diseases-and-mineral-disorders
#9
REVIEW
Siobhan Bacon, Rachel Crowley
In the last decade, there have been a number of significant advances made in the field of rare bone diseases. In this review, we discuss the expansion of the classification system for osteogenesis imperfecta (OI) and the resultant increase in therapeutic options available for management of OI. Bisphosphonates remain the most widely used intervention for OI, although the effect on fracture rate reduction is equivocal. We review the other therapies showing promising results, including denosumab, teriparatide, sclerostin, transforming growth factor β inhibition and gene targeted approaches...
January 2018: Therapeutic Advances in Chronic Disease
https://www.readbyqxmd.com/read/29179172/-control-of-bone-remodeling-by-bone-anabolic-drugs
#10
Yasuhiro Takeuchi
Teriparatide is a bone anabolic drug that is only available in practice. It is a N-terminal fragment of parathyroid hormone(PTH). Mode of actions of teriparatide is pharmacological but not physiological as it is administered to patients with osteoporosis. Physicians need to understand the fact that treatment with teriparatide is not just like a hormone replacement but its effects on bone remodeling are pharmacological. Romosozumab, under clinical development as anti-osteoporosis drug, is a monoclonal antibody against sclerostin...
2017: Clinical Calcium
https://www.readbyqxmd.com/read/29168393/serum-sclerostin-in-vascular-calcification-and-clinical-outcome-in-chronic-kidney-disease
#11
Cong Zeng, Chunyuan Guo, Juan Cai, Chengyuan Tang, Zheng Dong
Sclerostin, a potent soluble inhibitor of the Wnt signalling pathway, is known to inhibit bone formation by suppressing osteocytes differentiation and function. Patients with chronic kidney disease have high levels of serum sclerostin. Sclerostin has been implicated in the pathogenesis of vascular calcification, which may promote the cardiovascular events of morbidity and mortality in chronic kidney disease patients. However, the role of sclerostin in vascular calcification and clinical prognosis in chronic kidney disease remains elusive...
November 1, 2017: Diabetes & Vascular Disease Research
https://www.readbyqxmd.com/read/29113980/management-of-endocrine-disease-novel-anabolic-treatments-for-osteoporosis
#12
REVIEW
Ernesto Canalis
Skeletal anabolic agents enhance bone formation, which is determined by the number and function of osteoblasts. Signals that influence the differentiation and function of cells of the osteoblast lineage play a role in the mechanism of action of anabolic agents in the skeleton. Wnts induce the differentiation of mesenchymal stem cells toward osteoblasts, and insulin-like growth factor I (IGF-I) enhances the function of mature osteoblasts. The activity of Wnt and IGF-I is controlled by proteins that bind to the growth factor or to its receptors...
February 2018: European Journal of Endocrinology
https://www.readbyqxmd.com/read/29113523/monoclonal-antibodies-for-treating-osteoporosis
#13
Maria Felicia Faienza, Mariangela Chiarito, Gabriele D'amato, Graziana Colaianni, Silvia Colucci, Maria Grano, Giacomina Brunetti
Osteoporosis is the most widespread skeletal disease requiring innovative therapeutic strategies for its management. The understanding of receptor activator of nuclear factor kappa-B ligand (RANKL) and sclerostin's role in bone cell biology is completely changing the therapeutic landscape. RANKL supports osteoclast formation and activity and is mainly produced by cells of osteoblastic lineage. Sclerostin, an antagonist of the Wnt pathway, has a key role in bone formation and is mainly secreted by osteocytes...
November 7, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28974988/sclerostin-antibodies-in-osteoporosis-latest-evidence-and-therapeutic-potential
#14
REVIEW
Michael R McClung
Sclerostin is an osteocyte-derived glycoprotein that inhibits Wnt/β-catenin signaling and activation of osteoblast function, thereby inhibiting bone formation. It plays a vital role in the regulation of skeletal growth. In adults, sclerostin secretion is modulated by skeletal loading (increased secretion with immobilization; less with weight bearing) and by hormonal/cytokine actions on the osteocyte. Sclerostin deficiency syndromes in humans and animals are characterized by high bone mass of normal quality...
October 2017: Therapeutic Advances in Musculoskeletal Disease
https://www.readbyqxmd.com/read/28973221/sclerostin-blockade-and-zoledronic-acid-improve-bone-mass-and-strength-in-male-mice-with-exogenous-hyperthyroidism
#15
Elena Tsourdi, Franziska Lademann, Michael S Ominsky, Eddy Rijntjes, Josef Köhrle, Barbara M Misof, Paul Roschger, Klaus Klaushofer, Lorenz C Hofbauer, Martina Rauner
Hyperthyroidism in mice is associated with low bone mass, high bone turnover, and high concentrations of sclerostin, a potent Wnt inhibitor. Here, we explored the effects of either increasing bone formation with sclerostin antibodies (Scl-Ab) or reducing bone turnover with bisphosphonates on bone mass and strength in hyperthyroid mice. Twelve-week-old C57BL/6 male mice were rendered hyperthyroid using l-thyroxine (T4; 1.2 µg/mL added to the drinking water) and treated with 20 mg/kg Scl-Ab twice weekly or 100 µg/kg zoledronic acid (ZOL) once weekly or phosphate-buffered saline for 4 weeks...
November 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28860152/proteasome-inhibitor-bortezomib-is-a-novel-therapeutic-agent-for-focal-radiation-induced-osteoporosis
#16
Abhishek Chandra, Luqiang Wang, Tiffany Young, Leilei Zhong, Wei-Ju Tseng, Michael A Levine, Keith Cengel, X Sherry Liu, Yejia Zhang, Robert J Pignolo, Ling Qin
Bone atrophy and its related fragility fractures are frequent, late side effects of radiotherapy in cancer survivors and have a detrimental impact on their quality of life. In another study, we showed that parathyroid hormone 1-34 and anti-sclerostin antibody attenuates radiation-induced bone damage by accelerating DNA repair in osteoblasts. DNA damage responses are partially regulated by the ubiquitin proteasome pathway. In the current study, we examined whether proteasome inhibitors have similar bone-protective effects against radiation damage...
January 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28770650/osteoblast-as-a-target-of-anti-osteoporotic-treatment
#17
REVIEW
Addolorata Corrado, Eliana Rita Sanpaolo, Silvana Di Bello, Francesco Paolo Cantatore
Osteoblasts are mesenchymal cells that play a key role in maintaining bone homeostasis; they are responsible for the production of extracellular matrix proteins, regulation of matrix mineralization, control of bone remodeling and regulate osteoclast differentiation. Osteoblasts have an essential role in the pathogenesis of many bone diseases, particularly osteoporosis. For many decades, the main current available treatments for osteoporosis have been represented by anti-resorptive drugs, such as bisphosphonates, which act mainly by inhibiting osteoclasts maturation, proliferation and activity; nevertheless, in recent years much attention has been paid on anabolic aspects of osteoporosis treatment...
November 2017: Postgraduate Medicine
https://www.readbyqxmd.com/read/28647818/assessment-of-the-effect-of-systemic-delivery-of-sclerostin-antibodies-on-wnt-signaling-in-distraction-osteogenesis
#18
Mohammad M Alzahrani, Asim M Makhdom, Frank Rauch, Dominique Lauzier, Maria Kotsiopriftis, Saber Ghadakzadeh, Reggie C Hamdy
Sclerostin is a known inhibitor of the Wnt signaling pathway which is involved in osteogenesis and, when inactivated, stimulates bone formation. To our knowledge, this effect has not been studied in the context of distraction osteogenesis (DO). Tibial DO was conducted on a total of 24 wild-type mice, which were then divided into 2 groups-a saline injection group (control) and an anti-sclerostin (Scl-Ab) injection group (treatment). The mice in the treatment group received 100 mg/kg intravenous injections of the antibody weekly until killing...
June 24, 2017: Journal of Bone and Mineral Metabolism
https://www.readbyqxmd.com/read/28628032/osteocyte-specific-wnt1-regulates-osteoblast-function-during-bone-homeostasis
#19
Kyu Sang Joeng, Yi-Chien Lee, Joohyun Lim, Yuqing Chen, Ming-Ming Jiang, Elda Munivez, Catherine Ambrose, Brendan H Lee
Mutations in WNT1 cause osteogenesis imperfecta (OI) and early-onset osteoporosis, identifying it as a key Wnt ligand in human bone homeostasis. However, how and where WNT1 acts in bone are unclear. To address this mechanism, we generated late-osteoblast-specific and osteocyte-specific WNT1 loss- and gain-of-function mouse models. Deletion of Wnt1 in osteocytes resulted in low bone mass with spontaneous fractures similar to that observed in OI patients. Conversely, Wnt1 overexpression from osteocytes stimulated bone formation by increasing osteoblast number and activity, which was due in part to activation of mTORC1 signaling...
June 30, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28543818/bone-formation-is-coupled-to-resorption-via-suppression-of-sclerostin-expression-by-osteoclasts
#20
Masanori Koide, Yasuhiro Kobayashi, Teruhito Yamashita, Shunsuke Uehara, Midori Nakamura, B Yukihiro Hiraoka, Yuki Ozaki, Tadahiro Iimura, Hisataka Yasuda, Naoyuki Takahashi, Nobuyuki Udagawa
Bone formation is coupled to bone resorption throughout life. However, the coupling mechanisms are not fully elucidated. Using Tnfrsf11b-deficient (OPG(-/-) ) mice, in which bone formation is clearly coupled to bone resorption, we found here that osteoclasts suppress the expression of sclerostin, a Wnt antagonist, thereby promoting bone formation. Wnt/β-catenin signals were higher in OPG(-/-) and RANKL-transgenic mice with a low level of sclerostin. Conditioned medium from osteoclast cultures (Ocl-CM) suppressed sclerostin expression in UMR106 cells and osteocyte cultures...
May 24, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
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