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عنوان فارسی مقاله:

سلولهای میلوئید نابالغ برای افزایش بهبود شکستگی استخوان از طریق آبشار رگ زایی حیاتی


عنوان انگلیسی مقاله:

Immature myeloid cells are critical for enhancing bone fracture healing through angiogenic cascade


سال انتشار : 2016



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مقدمه انگلیسی مقاله:

1. Introduction

Each year, approximately 10–20% of the 6 million bone fractures in the United States will fail to heal, progressing to a condition termed nonunion [6]. Nonunion is defined as a fracture which has not healed 9 months post-occurrence, and has not shown any radiological progress within 3 months [30]. Nonunion occurs due to underlying pathologies that lead to either the fracture callus failing to fully ossify, or in atrophic cases, not forming altogether. At this point, aggressive and invasive treatment is required, which is associated with increased pain, disability, and treatment cost [5]. The gold-standard treatment for nonunion is currently internal stabilization of the bone via an intramedullary pin and screws, followed by autologous bone grafts from the iliac crest to promote osteoinductive signals [26]. However, this procedure has numerous inherent risks, including invasiveness, poor mechanical stability offered by the bone graft alone, and limited availability of bone from the iliac crest [18]. Therefore, novel, noninvasive approaches for treating nonunions should be investigated. Upon initial fracture, the traumatized tissues release various chemical signals, which recruits an influx of immune cells and osteogenic progenitors to fight infection and repair the fracture [16]. Several of these growth factors and cytokines, such as vascular endothelial growth factor (VEGF), bone morphogenetic proteins (BMPs) and interleukins (IL)-1 and -6 have been well characterized in recruiting inflammatory mediators to the fracture site [11]. Among the immune system cells are progenitors of the myeloid lineage, termed immature myeloid cells (IMCs). These IMCs comprise roughly 30% of all bone marrow cells, and under normal conditions eventually differentiate to macrophages, dendritic cells, and granulocytes [14]. However, their direct involvement in the inflammatory process following bone fracture has yet to be determined. IMC have been found to exert specific functions in other pathological contexts. In cancer, it was shown that IMC facilitate the induction of angiogenesis within tumors [15]. As with cancer, the injury site following fracture experiences elevated hypoxia as a byproduct of inflammation.It was recently shown that hypoxia-inducible factor (HIF) 1α couples angiogenesis with osteogenesis during bone early development [35]. Because nonunions are more likely to occur in conjunction with impaired angiogenesis [3,4], we sought to investigate the role IMCs may play in the coordination of angiogenesis with osteogenesis during bone fracture repair



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کلمات کلیدی:

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