Endogenous PTH deficiency impairs fracture healing and impedes the fracture-healing efficacy of exogenous PTH(1-34).
Endogenous PTH deficiency impairs fracture healing and impedes the fracture-healing efficacy of exogenous PTH(1-34).
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内源性PTH缺乏会损害骨折愈合并阻碍外源性PTH的骨折愈合功效(1-34)
DOI：
10.1371/journal.pone.0023060
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Miao D
中科院分区：
文献类型：
--
作者：
Ren Y;Liu B;Feng Y;Shu L;Cao X;Karaplis A;Goltzman D;Miao D
背景虽然外源性 PTH1-34 提高骨修复率的能力在动物模型中已得到充分证实，但我们对 PTH 在骨骼修复过程中诱导合成代谢反应的机制的了解仍然有限。此外，尚不清楚骨折愈合是否需要内源性 PTH，以及内源性 PTH 的缺乏将如何影响外源性 PTH 的骨折愈合能力。方法/主要发现 在 8 周大的野生型和 Pth null (Pth −/−) 小鼠中使用髓内钉制造闭合性股骨干中段骨折并进行稳定。小鼠在骨折后 1-4 周内每天接受赋形剂或 PTH1-34 (80 µg/kg) 注射，并在骨折后 1、2 和 4 周分析愈伤组织特性。分别与媒介物处理和 PTH 处理的野生型小鼠相比，媒介物处理和 PTH 处理的 Pth -/− 小鼠的软骨愈伤组织面积在骨折后 1 周减少，但在骨折后 2 周增加。与媒介物处理和 PTH 处理的野生型小鼠相比，媒介物处理和 PTH 处理的 Pth −/− 小鼠中矿化愈伤组织面积、骨愈伤组织面积、成骨细胞数量和活性、破骨细胞数量和愈伤组织表面均减少，但与媒介物处理的野生型和 Pth −/− 小鼠相比，PTH 处理的野生型和 Pth −/− 小鼠增加。结论/意义 内源性 PTH1-84 的缺失会阻碍骨折愈合。外源性 PTH1-34 可以在缺乏内源性 PTH 的情况下发挥作用，但当存在内源性 PTH 时，愈伤组织形成（包括加速软骨内骨形成和愈伤组织重塑）以及骨的机械强度会更大。这项研究的结果表明内源性 PTH1-84 和外源性 PTH1-34 在加速骨折愈合方面具有互补作用。
Background Although the capacity of exogenous PTH1-34 to enhance the rate of bone repair is well established in animal models, our understanding of the mechanism(s) whereby PTH induces an anabolic response during skeletal repair remains limited. Furthermore it is unknown whether endogenous PTH is required for fracture healing and how the absence of endogenous PTH would influence the fracture-healing capacity of exogenous PTH. Methodology/Principal Findings Closed mid-diaphyseal femur fractures were created and stabilized with an intramedullary pin in 8-week-old wild-type and Pth null (Pth −/−) mice. Mice received daily injections of vehicle or of PTH1-34 (80 µg/kg) for 1–4 weeks post-fracture, and callus tissue properties were analyzed at 1, 2 and 4 weeks post-fracture. Cartilaginous callus areas were reduced at 1 week post-fracture, but were increased at 2 weeks post-fracture in vehicle-treated and PTH-treated Pth −/− mice compared to vehicle-treated and PTH-treated wild-type mice respectively. The mineralized callus areas, bony callus areas, osteoblast number and activity, osteoclast number and surface in callus tissues were all reduced in vehicle-treated and PTH-treated Pth −/− mice compared to vehicle-treated and PTH-treated wild-type mice, but were increased in PTH-treated wild-type and Pth −/− mice compared to vehicle-treated wild-type and Pth −/− mice. Conclusions/Significance Absence of endogenous PTH1-84 impedes bone fracture healing. Exogenous PTH1-34 can act in the absence of endogenous PTH but callus formation, including accelerated endochondral bone formation and callus remodeling as well as mechanical strength of the bone are greater when endogenous PTH is present. Results of this study suggest a complementary role for endogenous PTH1-84 and exogenous PTH1-34 in accelerating fracture healing.
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影响因子：
2.3
作者：
Miao D;Scutt A
通讯作者：
Scutt A
影响因子：
4.8
作者：
Miao, DS;He, B;Karaplis, AC
通讯作者：
Karaplis, AC
影响因子：
6.2
作者：
Andreassen, TT;Ejersted, C;Oxlund, H
通讯作者：
Oxlund, H
DOI：
10.1097/00003086-199909000-00033
发表时间：
1999-09-01
影响因子：
4.2
作者：
Holzer, G;Majeska, RJ;Einhorn, TA
通讯作者：
Einhorn, TA
影响因子：
6.2
作者：
Kakar, Sanjeev;Einhorn, Thomas A.;Barnes, George L.
通讯作者：
Barnes, George L.