کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5585115 | 1568123 | 2017 | 53 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Effects of sclerostin antibodies in animal models of osteoporosis
ترجمه فارسی عنوان
اثرات آنتیبادی های اسکلروستین در مدل های حیوانی پوکی استخوان
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
pTHOVXovariectomizedZDFCKD-MBDCTXBFR/BSFGF23BSEMFTIRMDXADMP1P1NPDKK1PDLLRP4PKDpQCTMBFhPTHTNFαTRACP-5bBMDcarboxy-terminal collagen crosslinksRBFDEXRUNX2LCMAUC - AUCAln - آلنAlendronate - آلندروناتAnti-drug antibody - آنتی بادی ضد داروSclerostin antibody - آنتیبادی اسکلروستینpolycystic kidney disease - بیماری کلیوی پلی کیستیکBone mineral density - تراکم معدنی استخوانBone formation - تشکیل استخوان tumor necrosis factor-alpha - تومور نکروز عامل آلفاdual-energy X-ray absorptiometry - جذب اندازه گیری اشعه ایکس دوگانه انرژیDexamethasone - دگزامتازونPeriodontal ligament - رباط پریودنتالRomosozumab - رموزوموآبWall thickness - ضخامت دیوارRunt-related transcription factor 2 - عامل رونویسی مرتبط با روت 2fibroblast growth factor 23 - فاکتور رشد فیبروبلاست 23laser capture microdissection - لیزر ضبط میکرو دیسکسیونperipheral Quantitative Computed Tomography - محاسبات کمی محاسبات محوریAnimal models - مدل های حیوانیarea under curve - منطقه تحت منحنیMultiple myeloma - مولتیپل میلوماparathyroid hormone - هورمون پاراتیروئیدHuman parathyroid hormone - هورمون پاراتیروئید انسانADA - وجود داردdentin matrix protein 1 - پروتئین ماتریکس دنتین 1Osteoporosis - پوکی استخوانZucker Diabetic Fatty - چربی دیابتی ZuckerBone quality - کیفیت استخوانGlucocorticoids - گلوکوکورتیکوئیدها
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شناسی تکاملی
چکیده انگلیسی
There is an unmet need for therapies that can restore bone strength and reduce fracture risk among patients at high risk of osteoporotic fracture. To address this need, bone-forming therapies that increase osteoblast activity are required to help restore bone structure and strength. Sclerostin is now recognized as a target for osteoporosis therapy. Sclerostin is predominantly secreted by the osteocyte and acts as an extracellular inhibitor of canonical Wnt signaling by binding to the receptors lipoprotein receptor-related protein-4, 5 and 6. Monoclonal antibodies to sclerostin (Scl-Ab) have been used in both clinical and in preclinical studies of osteoporosis with beneficial outcomes for bone density, structure, strength and fracture risk reduction. In this review paper, we summarize the current literature describing the effects of Scl-Ab in animal models of osteoporosis. In addition, we report new pharmacologic data from three animal studies of Scl-Ab: 1) a 12-month study evaluating bone quality in ovariectomized (OVX) rats; 2) a 6-month study evaluating bone structure and strength in adolescent cynomolgus monkeys; and 3) the effects of transition from Scl-Ab to vehicle or the RANKL inhibitor osteoprotegerin-Fc in OVX rats. Together, these results demonstrate that inhibition of sclerostin by Scl-Ab increased bone formation, and decreased bone resorption, leading to improved bone structure, bone mass and bone strength while maintaining bone quality in multiple animal models of osteoporosis. Further, gains in bone mass induced by Scl-Ab treatment were preserved by antiresorptive agents such as a RANKL inhibitor as a follow-on therapy. The bone-forming effects of Scl-Ab were unaffected by pre- or co-treatment with a bisphosphonate, and were restored following a treatment-free period after initial dosing. These data support the clinical development of Scl-Ab for treatment of conditions with low bone mass such as postmenopausal and male osteoporosis.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bone - Volume 96, March 2017, Pages 63-75
Journal: Bone - Volume 96, March 2017, Pages 63-75
نویسندگان
Michael Stuart Ominsky, Rogely Waite Boyce, Xiaodong Li, Hua Zhu Ke,