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排序方式: 共有928条查询结果,搜索用时 12 毫秒
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Sanjeev Kakar Thomas A Einhorn Siddharth Vora Lincoln J Miara Gregory Hon Nathan A Wigner Daniel Toben Kimberly A Jacobsen Maisa O Al-Sebaei Michael Song Philip C Trackman Elise F Morgan Louis C Gerstenfeld George L Barnes 《Journal of bone and mineral research》2007,22(12):1903-1912
Studies have shown that systemic PTH treatment enhanced the rate of bone repair in rodent models. However, the mechanisms through which PTH affects bone repair have not been elucidated. In these studies we show that PTH primarily enhanced the earliest stages of endochondral bone repair by increasing chondrocyte recruitment and rate of differentiation. In coordination with these cellular events, we observed an increased level of canonical Wnt-signaling in PTH-treated bones at multiple time-points across the time-course of fracture repair, supporting the conclusion that PTH responses are at least in part mediated through Wnt signaling. INTRODUCTION: Since FDA approval of PTH [PTH(1-34); Forteo] as a treatment for osteoporosis, there has been interest in its use in other musculoskeletal conditions. Fracture repair is one area in which PTH may have a significant clinical impact. Multiple animal studies have shown that systemic PTH treatment of healing fractures increased both callus volume and return of mechanical competence in models of fracture healing. Whereas the potential for PTH has been established, the mechanism(s) by which PTH produces these effects remain elusive. MATERIALS AND METHODS: Closed femoral fractures were generated in 8-wk-old male C57Bl/6 mice followed by daily systemic injections of either saline (control) or 30 microg/kg PTH(1-34) for 14 days after fracture. Bones were harvested at days 2, 3, 5, 7, 10, 14, 21, and 28 after fracture and analyzed at the tissue level by radiography and histomorphometry and at the molecular and biochemical levels level by RNase protection assay (RPA), real-time PCR, and Western blot analysis. RESULTS: Quantitative muCT analysis showed that PTH treatment induced a larger callus cross-sectional area, length, and total volume compared with controls. Molecular analysis of the expression of extracellular matrix genes associated with chondrogenesis and osteogenesis showed that PTH treated fractures displayed a 3-fold greater increase in chondrogenesis relative to osteogenesis over the course of the repair process. In addition, chondrocyte hypertrophy occurred earlier in the PTH-treated callus tissues. Analysis of the expression of potential mediators of PTH actions showed that PTH treatment significantly induced the expression of Wnts 4, 5a, 5b, and 10b and increased levels of unphosphorylated, nuclear localized beta-catenin protein, a central feature of canonical Wnt signaling. CONCLUSIONS: These results showed that the PTH-mediated enhancement of fracture repair is primarily associated with an amplification of chondrocyte recruitment and maturation in the early fracture callus. Associated with these cellular effects, we observed an increase in canonical Wnt signaling supporting the conclusion that PTH effects on bone repair are mediated at least in part through the activation of Wnt-signaling pathways. 相似文献
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Siddharth K. Prakash Soniely Lugo‐Ruiz Michelle Rivera‐Dávila Nunilo Rubio Jr. Avni N. Shah Rebecca C. Knickmeyer Cindy Scurlock Melissa Crenshaw Shanlee M. Davis Gary A. Lorigan Aaron T. Dorfman Karen Rubin Cheryl Maslen Vaneeta Bamba Paul Kruszka Michael Silberbach Scientific Advisory Board of the TSRR 《American journal of medical genetics. Part C, Seminars in medical genetics》2019,181(1):7-12
To address knowledge gaps about Turner syndrome (TS) associated disease mechanisms, the Turner Syndrome Society of the United States created the Turner Syndrome Research Registry (TSRR), a patient‐powered registry for girls and women with TS. More than 600 participants, parents or guardians completed a 33‐item foundational survey that included questions about demographics, medical conditions, psychological conditions, sexuality, hormonal therapy, patient and provider knowledge about TS, and patient satisfaction. The TSRR platform is engineered to allow individuals living with rare conditions and investigators to work side‐by‐side. The purpose of this article is to introduce the concept, architecture, and currently available content of the TSRR, in anticipation of inviting proposals to utilize registry resources. 相似文献
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Siddharth K. Prakash 《American journal of medical genetics. Part C, Seminars in medical genetics》2019,181(1):110-115
Somatic mosaicism is a major modifier of turner syndrome (TS) features and may be more prevalent than once thought, as new molecular techniques enable detection of tissue‐specific mosaicism. This review explores the causes of mosaicism, discusses how mosaicism may impact congenital aortic defects in TS, and summarizes molecular methods to detect mosaicism in different contexts. 相似文献
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Deepika D'Cunha Burkardt Anna Zachariou Chey Loveday Clare L. Allen David J. Amor Anna Ardissone Siddharth Banka Alexia Bourgois Christine Coubes Cheryl Cytrynbaum Laurence Faivre Gerard Marion Rachel Horton Dieter Kotzot Guillermo Lay‐Son Melissa Lees Karen Low Ho‐Ming Luk Paul Mark Allyn McConkie‐Rosell Marie McDonald John Pappas Christophe Phillipe Deborah Shears Brian Skotko Fiona Stewart Helen Stewart I Karen. Temple Frederic T. Mau‐Them Ricardo A. Verdugo Rosanna Weksberg Yuri A. Zarate John M. Graham Katrina Tatton‐Brown 《American journal of medical genetics. Part A》2019,179(10):2049-2055
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Gauri Mishra Anouk Dev Eldho Paul William Kemp Ammar Majeed John Lubel Sally Bell Paul Gow Amanda Nicoll Siddharth Sood Alex Thompson Marno Ryan Stuart K.Roberts 《肝癌研究(英文版)》2021,(7):66-79
Aim: Transarterial chemoembolisation (TACE) is recommended therapy for intermediate-stage hepatocellular carcinoma (HCC). However, the wide variations in outcom... 相似文献