甲状旁腺激素促进同种异体移植物在颅骨骨缺损中的整合。

PTH promotes allograft integration in a calvarial bone defect.

机构信息

Department of Surgery, Cedars-Sinai Medical Center , Los Angeles, California 90048, United States.

出版信息

Mol Pharm. 2013 Dec 2;10(12):4462-71. doi: 10.1021/mp400292p. Epub 2013 Nov 8.

Abstract

Allografts may be useful in craniofacial bone repair, although they often fail to integrate with the host bone. We hypothesized that intermittent administration of parathyroid hormone (PTH) would enhance mesenchymal stem cell recruitment and differentiation, resulting in allograft osseointegration in cranial membranous bones. Calvarial bone defects were created in transgenic mice, in which luciferase is expressed under the control of the osteocalcin promoter. The mice were given implants of allografts with or without daily PTH treatment. Bioluminescence imaging (BLI) was performed to monitor host osteprogenitor differentiation at the implantation site. Bone formation was evaluated with the aid of fluorescence imaging (FLI) and microcomputed tomography (μCT) as well as histological analyses. Reverse transcription polymerase chain reaction (RT-PCR) was performed to evaluate the expression of key osteogenic and angiogenic genes. Osteoprogenitor differentiation, as detected by BLI, in mice treated with an allograft implant and PTH was over 2-fold higher than those in mice treated with an allograft implant without PTH. FLI also demonstrated that the bone mineralization process in PTH-treated allografts was significantly higher than that in untreated allografts. The μCT scans revealed a significant increase in bone formation in allograft + PTH treated mice comparing to allograft + PBS treated mice. The osteogenic genes osteocalcin (Oc/Bglap) and integrin binding sialoprotein (Ibsp) were upregulated in the allograft + PTH treated animals. In summary, PTH treatment enhances osteoprogenitor differentiation and augments bone formation around structural allografts. The precise mechanism is not clear, but we show that infiltration pattern of mast cells, associated with the formation of fibrotic tissue, in the defect site is significantly affected by the PTH treatment.

摘要

同种异体移植物可用于颅颌面骨修复,但它们往往不能与宿主骨整合。我们假设,甲状旁腺激素(PTH)的间歇性给药会增强间充质干细胞的募集和分化,从而导致颅膜状骨同种异体移植物的骨整合。在荧光素酶在骨钙素启动子控制下表达的转基因小鼠中创建了颅骨骨缺损。将同种异体移植物植入小鼠体内,有些给予每日 PTH 治疗,有些则不给予。通过生物发光成像(BLI)监测植入部位宿主成骨前体细胞的分化。通过荧光成像(FLI)、微计算机断层扫描(μCT)和组织学分析评估骨形成。通过逆转录聚合酶链反应(RT-PCR)评估关键成骨和血管生成基因的表达。通过 BLI 检测到的同种异体移植物植入和 PTH 治疗的小鼠中成骨前体细胞的分化是未接受 PTH 治疗的同种异体移植物植入小鼠的 2 倍以上。FLI 还表明,PTH 处理的同种异体移植物中的骨矿化过程明显高于未处理的同种异体移植物。μCT 扫描显示,与 PBS 处理的同种异体移植物相比,PTH 处理的同种异体移植物+PTH 处理的小鼠的骨形成显著增加。在同种异体移植物+PTH 治疗的动物中,骨钙素(Oc/Bglap)和整合素结合唾液蛋白(Ibsp)等成骨基因上调。总之,PTH 治疗可增强成骨前体细胞的分化,并增强结构同种异体移植物周围的骨形成。确切的机制尚不清楚,但我们表明,与纤维组织形成相关的肥大细胞在缺陷部位的浸润模式受 PTH 治疗的显著影响。

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