Wnt3a Reestablishes Osteogenic Capacity to Bone Grafts from Aged Animals
Wnt3a Reestablishes Osteogenic Capacity to Bone Grafts from Aged Animals
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DOI：
10.2106/jbjs.l01502
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发表时间：
2013-07-17
影响因子：
5.3
通讯作者：
Helms, Jill A.
中科院分区：
文献类型：
--
作者：
Leucht, Philipp;Jiang, Jie;Helms, Jill A.
背景资料：骨髓脂肪变性是导致老年人骨折愈合延迟和骨质疏松相关骨折的原因之一。这种脂肪的变化的机制是未知的，但它们可能涉及到Wnt信号的水平内的老年marine cavity.Methods：转基因小鼠与同基因骨移植模型一起使用，以遵循参与移植的细胞的命运。免疫组织化学沿着定量分析用于评估来自年轻和老年小鼠的骨移植物中的Wnt信号传导和成脂和成骨基因表达。脂质体Wnt 3a蛋白（L-Wnt 3a）在小鼠和兔中建立的临界大小缺损模型中测试其恢复老化骨移植物成骨潜力的能力。射线照相术，显微定量计算机断层扫描（micro-CT）重建，组织学，和组织形态测量被用来量化骨愈合导致L-Wnt 3a或对照物质（脂质体磷酸盐缓冲盐水溶液EL-PBS]）。结果：在骨移植细胞的表达谱证明了一个转变远离成骨基因的档案，并朝着成脂的一个与年龄。这种年龄相关的脂肪形成转变伴随着Wnt信号传导的显著减少（p < 0.05）和成骨潜能的丧失。在大型和小型动物模型中，通过与干细胞因子Wnt 3a进行短暂孵育，老年骨移植物的成骨能力得以恢复。此外，脂质体Wnt 3a显着减少细胞死亡的骨移植，导致显着更多的骨再生相比controls.Conclusions：脂质体Wnt 3a增强细胞的生存和重建成骨能力的骨移植从老年animals.Clinical Relevance：我们开发了一种有效的，临床适用的，再生医学为基础的战略，振兴骨移植从老年患者。
Background: Age-related fatty degeneration of the bone marrow contributes to delayed fracture-healing and osteoporosis-related fractures in the elderly. The mechanisms underlying this fatty change are unknown, but they may relate to the level of Wnt signaling within the aged marrow cavity.Methods: Transgenic mice were used in conjunction with a syngeneic bone-graft model to follow the fates of cells involved in the engraftment. Immunohistochemistry along with quantitative assays were used to evaluate Wnt signaling and adipogenic and osteogenic gene expression in bone grafts from young and aged mice. Liposomal Wnt3a protein (L-Wnt3a) was tested for its ability to restore osteogenic potential to aged bone grafts in critical-size defect models created in mice and in rabbits. Radiography, microquantitative computed tomography (micro-CT) reconstruction, histology, and histomorphometric measurements were used to quantify bone-healing resulting from L-Wnt3a or a control substance (liposomal phosphate-buffered saline solution EL-PBS]).Results: Expression profiling of cells in a bone graft demonstrated a shift away from an osteogenic gene profile and toward an adipogenic one with age. This age-related adipogenic shift was accompanied by a significant reduction (p < 0.05) in Wnt signaling and a loss in osteogenic potential. In both large and small animal models, osteogenic competence was restored to aged bone grafts by a brief incubation with the stem-cell factor Wnt3a. In addition, liposomal Wnt3a significantly reduced cell death in the bone graft, resulting in significantly more osseous regenerate in comparison with controls.Conclusions: Liposomal Wnt3a enhances cell survival and reestablishes the osteogenic capacity of bone grafts from aged animals.Clinical Relevance: We developed an effective, clinically applicable, regenerative medicine-based strategy for revitalizing bone grafts from aged patients.