Hildreth Blake Eason, Williams Michelle M, Dembek Katarzyna A, Hernon Krista M, Rosol Thomas J, Toribio Ramiro E
Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, 43210, USA.
Small Animal Imaging Center, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA.
Transgenic Res. 2015 Dec;24(6):955-69. doi: 10.1007/s11248-015-9901-9. Epub 2015 Aug 14.
Evidence exists that parathyroid hormone-related protein (PTHrP) 1-34 may be more anabolic in bone than parathyroid hormone 1-34. While optical imaging is growing in popularity, scant information exists on the relationships between traditional bone imaging and histology and bioluminescence (BLI) and fluorescence (FLI) imaging. We aimed to evaluate the effects of PTHrP 1-34 on bone mass and determine if relationships existed between radiographic and histologic findings in bone and BLI and FLI indices. Vertebrae (vossicles) from mice coexpressing luciferase and green fluorescent protein were implanted subcutaneously into allogenic nude mice. Transplant recipients were treated daily with saline or PTHrP 1-34 for 4 weeks. BLI, FLI, radiography, histology, and µCT of the vossicles were performed over time. PTHrP 1-34 increased bioluminescence the most after 2 weeks, fluorescence at all time points, and decreased the time to peak bioluminescence at 4 weeks (P ≤ 0.027), the latter of which suggesting enhanced engraftment. PTHrP 1-34 maximized vertebral body volume at 4 weeks (P < 0.0001). The total amount of bone observed histologically increased in both groups at 2 and 4 weeks (P ≤ 0.002); however, PTHrP 1-34 exceeded time-matched controls (P ≤ 0.044). A positive linear relationship existed between the percentage of trabecular bone and (1) total bioluminescence (r = 0.595; P = 0.019); (2) total fluorescence (r = 0.474; P = 0.074); and (3) max fluorescence (r = 0.587; P = 0.021). In conclusion, PTHrP 1-34 enhances engraftment and bone mass, which can be monitored non-invasively by BLI and FLI.
有证据表明,甲状旁腺激素相关蛋白(PTHrP)1-34在骨骼中的合成代谢作用可能比甲状旁腺激素1-34更强。虽然光学成像越来越受欢迎,但关于传统骨成像与组织学以及生物发光(BLI)和荧光(FLI)成像之间的关系,现有信息却很少。我们旨在评估PTHrP 1-34对骨量的影响,并确定骨的放射学和组织学结果与BLI和FLI指标之间是否存在关联。将共表达荧光素酶和绿色荧光蛋白的小鼠椎骨(小骨块)皮下植入同种异体裸鼠体内。移植受体每天接受生理盐水或PTHrP 1-34治疗,持续4周。随时间推移对小骨块进行BLI、FLI、放射学、组织学和显微CT检查。PTHrP 1-34在2周后使生物发光增强最多,在所有时间点均使荧光增强,并在4周时缩短了生物发光峰值出现的时间(P≤0.027),后者表明植入增强。PTHrP 1-34在4周时使椎体体积最大化(P<0.0001)。组织学观察到的两组骨总量在2周和4周时均增加(P≤0.002);然而,PTHrP 1-34超过了时间匹配的对照组(P≤0.044)。小梁骨百分比与(1)总生物发光(r = 0.595;P = 0.019);(2)总荧光(r = 0.474;P = 0.074);以及(3)最大荧光(r = 0.587;P = 0.021)之间存在正线性关系。总之,PTHrP 1-34增强了植入和骨量,可通过BLI和FLI进行无创监测。