COX-2 from the injury milieu is critical for the initiation of periosteal progenitor cell mediated bone healing.
COX-2 from the injury milieu is critical for the initiation of periosteal progenitor cell mediated bone healing.
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DOI：
10.1016/j.bone.2008.08.109
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发表时间：
2008-12
期刊：
影响因子：
4.1
通讯作者：
Zhang, Xinping
中科院分区：
文献类型：
--
作者：
Xie, Chao;Ming, Xue;Wang, Qun;Schwarz, Edward M.;Guldberg, Robert E.;O'Keefe, Regis J.;Zhang, Xinping
虽然考克斯-2在骨修复中的重要作用已被证实，但其机制尚不清楚。在骨愈合的早期炎症阶段，考克斯-2由周围的炎性细胞以及骨/软骨祖细胞产生。基于考克斯-2在骨折愈合早期的时间和空间表达，我们假设来自两个来源的考克斯-2对祖细胞活化、增殖和分化是至关重要的。为了直接测试这一点，我们利用了小鼠股骨移植模型，其中移植了来自相同品系的活节段移植物，并评估了供体与宿主细胞参与愈合的情况。具体而言，将来自考克斯-2-/-（KO）小鼠的4 mm长的新鲜股骨皮质骨移植物移植到股骨中具有相同尺寸节段性缺损的野生型（WT）小鼠中。类似地，将来自WT的移植物移植到KO小鼠的缺陷中。作为对照，还进行了野生型之间的移植和KO之间的移植。组织学分析表明，WT-WT移植导致正常的软骨内骨愈合，这通过显著诱导供体移植物上的新血管形成和骨膜骨形成来证明。相比之下，KO移植物移植到KO宿主中导致骨形成减少96%，并且几乎消除了供体细胞引发的骨膜骨形成。类似地，将WT移植物移植到KO宿主中导致骨形成减少87%（n=8，p>0.05），表明KO宿主损害WT供体祖细胞扩增和分化。当KO移植物移植到WT宿主中时，KO供体骨膜细胞启动的软骨内骨形成得以恢复。组织形态测定分析表明，与KO-至-KO移植相比，骨形成增加10倍，软骨形成增加3倍（n=8，p<0.05），表明当置于WT宿主中时，考克斯-2缺陷型供体细胞能够分化并形成骨。综上所述，我们的数据有力地表明，考克斯-2是至关重要的骨膜皮质骨愈合的启动。考克斯-2的早期诱导为供体骨膜祖细胞的活化和分化构成了一个关键的宿主愈合环境。在愈合早期消除考克斯-2可能会对骨膜祖细胞启动的皮质骨修复产生不利影响。
Although a critical role of COX-2 in bone repair has been established, the mechanism involved remains unclear. During early inflammatory phase of bone healing, COX-2 is produced by the surrounding inflammatory cells as well as bone/cartilage progenitors. Based on the temporal and spatial expression of COX-2 during the early phase of fracture healing, we hypothesize that COX-2 from both sources is critical for progenitor cell activation, proliferation and differentiation. To directly test this we utilized a murine femoral grafting model, in which live segmental grafts from the same strains were transplanted and donor versus host cell involvement in healing was assessed. Specifically, fresh femur cortical bone grafts of 4-mm in length from COX-2-/- (KO) mice were transplanted into wild type (WT) mice with the same sized segmental defect in femurs. Similarly, grafts from WT were transplanted into the defects in KO mice. As controls, transplantations between wild types, and transplantations between KO were also performed. Histologic analyses showed that WT-to-WT transplantation resulted in normal endochondral bone healing as evidenced by markedly induction of neovascularization and periosteal bone formation on donor graft. In contrast, transplantation of KO graft into KO host led to 96 % reduction of bone formation and near elimination of donor cell-initiated periosteal bone formation. Similarly, transplantation of WT graft into a KO host resulted in 87% reduction of bone formation (n=8, p>0.05), indicating that KO host impaired WT donor progenitor cell expansion and differentiation. When a KO graft was transplanted into WT host, KO donor periosteal cell-initiated endochondral bone formation was restored. Histomorphometric analyses demonstrated 10-fold increase in bone formation and 3-fold increase in cartilage formation compared to KO-to-KO transplantation (n=8, p<0.05), suggesting that COX-2 deficient donor cells were capable to differentiate and form bone when placed in a WT host. Taken together, our data strongly suggest that COX-2 is critical for initiation of periosteal cortical bone healing. The early induction of COX-2 constitutes a crucial host-healing environment for activation and differentiation of donor periosteal progenitors. Elimination of COX-2 at the early stage of healing could lead to detrimental effects on periosteal progenitor cell-initiated cortical bone repair.
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影响因子：
6.2
作者：
Barnes, GL;Kostenuik, PJ;Einhorn, TA
通讯作者：
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