Sostdc1 deficiency accelerates fracture healing by promoting the expansion of periosteal mesenchymal stem cells.
Sostdc1 deficiency accelerates fracture healing by promoting the expansion of periosteal mesenchymal stem cells.
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DOI：
10.1016/j.bone.2016.04.005
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发表时间：
2016-07
期刊：
影响因子：
4.1
通讯作者：
Loots GG
中科院分区：
文献类型：
--
作者：
Collette NM;Yee CS;Hum NR;Murugesh DK;Christiansen BA;Xie L;Economides AN;Manilay JO;Robling AG;Loots GG
Sostdc 1是一种与Sost类似的生长因子，其缺失会导致异位切牙、融合磨牙、异常毛囊和对肾脏疾病的抵抗力的形成。Sostdc 1在骨膜中表达，骨膜是成骨细胞、成纤维细胞和间充质祖细胞的来源，这些细胞对于骨折修复至关重要。在这里，我们研究了Sostdc 1在骨代谢和骨折修复中的作用。缺乏Sostdc 1（Sostdc 1 −/−）的小鼠具有低骨量表型，与腰椎和无骨骨骼中的松质骨丢失相关。相比之下，Sostdc 1 −/−皮质骨测量结果显示骨较大，BMD较高，这表明Sostdc 1对皮质骨和松质骨产生不同的影响。在Sostdc 1 −/−小鼠中诱导的股骨中段骨折表明，通常对Sostdc 1呈阳性的骨膜群体在骨膜增厚期间迅速扩张，并且这些细胞在骨折后3天迁移到骨折骨痂中。间充质干细胞（MSC）和成骨细胞群体的定量分析确定MSC表达Sostdc 1，并且Sostdc 1 −/− 5天的愈伤组织比骨折的野生型对照多2倍。在组织学上，一部分Sostdc 1阳性细胞也表达巢蛋白和α-平滑肌肌动蛋白，表明Sostdc 1标志着一群积极参与骨痂形成和骨修复的骨软骨祖细胞。D5愈伤组织中MSC数量的增加导致在第7天出现更大、更血管化的软骨愈伤组织，并且在骨折后21天软骨更新更快，具有显著更多的重塑骨和更厚的皮质壳。这些数据支持Sostdc 1 −/−小鼠中加速或增强的骨形成/骨痂重塑，表明Sostdc 1可能促进和维持骨膜中的间充质干细胞静止。
Loss of Sostdc1, a growth factor paralogous to Sost, causes the formation of ectopic incisors, fused molars, abnormal hair follicles, and resistance to kidney disease. Sostdc1 is expressed in the periosteum, a source of osteoblasts, fibroblasts and mesenchymal progenitor cells, which are critically important for fracture repair. Here, we investigated the role of Sostdc1 in bone metabolism and fracture repair. Mice lacking Sostdc1 (Sostdc1−/−) had a low bone mass phenotype associated with loss of trabecular bone in both lumbar vertebrae and in the appendicular skeleton. In contrast, Sostdc1−/− cortical bone measurements revealed larger bones with higher BMD, suggesting that Sostdc1 exerts differential effects on cortical and trabecular bone. Mid-diaphyseal femoral fractures induced in Sostdc1−/− mice showed that the periosteal population normally positive for Sostdc1 rapidly expands during periosteal thickening and these cells migrate into the fracture callus at 3 days post fracture. Quantitative analysis of mesenchymal stem cell (MSC) and osteoblast populations determined that MSCs express Sostdc1, and that Sostdc1−/− 5 day calluses harbor >2-fold more MSCs than fractured wildtype controls. Histologically a fraction of Sostdc1-positive cells also expressed nestin and α-smooth muscle actin, suggesting that Sostdc1 marks a population of osteochondral progenitor cells that actively participate in callus formation and bone repair. Elevated numbers of MSCs in D5 calluses resulted in a larger, more vascularized cartilage callus at day 7, and a more rapid turnover of cartilage with significantly more remodeled bone and a thicker cortical shell at 21 days post fracture. These data support accelerated or enhanced bone formation/remodeling of the callus in Sostdc1−/− mice, suggesting that Sostdc1 may promote and maintain mesenchymal stem cell quiescence in the periosteum.
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影响因子：
4.3
作者：
Liu, Shuang;Zhang, Enjiao;Lu, Li
通讯作者：
Lu, Li
影响因子：
5.2
作者：
Grcevic, Danka;Pejda, Slavica;Matthews, Brya G.;Repic, Dario;Wang, Liping;Li, Haitao;Kronenberg, Mark S.;Jiang, Xi;Maye, Peter;Adams, Douglas J.;Rowe, David W.;Aguila, Hector L.;Kalajzic, Ivo
通讯作者：
Kalajzic, Ivo
影响因子：
2.7
作者：
Collette, Nicole M.;Genetos, Damian C.;Murugesh, Deepa;Harland, Richard M.;Loots, Gabriela G.
通讯作者：
Loots, Gabriela G.
影响因子：
2.7
作者：
Laurikkala, J;Kassai, Y;Itoh, N
通讯作者：
Itoh, N
DOI：
10.1002/jbmr.2140
发表时间：
2014
期刊：
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
影响因子：
--
作者：
Matthews BG;Grcevic D;Wang L;Hagiwara Y;Roguljic H;Joshi P;Shin DG;Adams DJ;Kalajzic I
通讯作者：
Kalajzic I