Laboratoire de Bioingénierie et Biomécanique Ostéo-articulaires, UMR CNRS 7052, CNRS INSIS, Université Paris Diderot Sorbonne Paris Cité, Paris, France.
Laboratoire de Bioingénierie et Biomécanique Ostéo-articulaires, UMR CNRS 7052, CNRS INSIS, Université Paris Diderot Sorbonne Paris Cité, Paris, France; Department of Periodontology, Service of Odontology, Pitié Salpêtrière Hospital, U.F.R. of Odontology Paris 7-Denis Diderot University, Sorbonne Paris Cité Paris, France.
Bone. 2018 Jul;112:161-172. doi: 10.1016/j.bone.2018.04.009. Epub 2018 Apr 25.
The present study was motivated by the fact that bone regeneration in the compromised vascular microenvironment of T2DM is challenging and the factors that determine the adverse bone regeneration outcomes are poorly understood. For this purpose the effect of T2DM on osteogenic and angiogenic healing potential of calvarial bone, was evaluated in Zucker diabetic fatty (ZDF) rats, an established rat model for obese T2DM.
The study used 16-week-old ZDF rats and their age-matched controls, Zucker Lean (ZL). Circular defects of different sizes were created on the animal calvaria, either a single 8-mm-diameter (n = 6) defect, or 6-4-2-mm-diameter multidefects (n = 6). Bone regeneration was evaluated at 0, 4, 6 and 8 weeks post surgery using in vivo micro-CT and after animal sacrifice using ex vivo micro-CT. Vascular network parameters within the defects, were quantified by perfusing the animal vasculature with microfil® and scanning it after decalcification.
Compared to results obtained from the ZL rats, defects of 8-mm-diameter in ZDF rats displayed impaired healing kinetics and significantly reduced newly formed bone volume (p < 0.01) and surface area (p < 0.01), 8 weeks post surgery. Defects of 6-4-2-mm-diameter exhibited bone formation, which was independent of either the size or the diabetic condition. Compared to results from the ZL, in the ZDF rats, vasculature volume and surface area were significantly (p < 0.05) reduced in all size-defects.
The present study provided evidence that T2DM impairs bone formation in critical-size calvarial defects and markedly reduces angiogenesis in all defects regardless of the defect size tested.
本研究的动机是，在 T2DM 受损的血管微环境中，骨再生具有挑战性，并且导致不良骨再生结果的因素尚未得到充分理解。为此，本研究评估了 T2DM 对 Zucker 糖尿病肥胖（ZDF）大鼠颅骨的成骨和血管生成愈合潜力的影响，ZDF 大鼠是肥胖 T2DM 的一种已建立的大鼠模型。
本研究使用了 16 周龄的 ZDF 大鼠及其年龄匹配的对照 Zucker 瘦鼠（ZL）。在动物颅骨上制造不同大小的圆形缺损，包括单个 8-mm 直径（n=6）缺损或 6-4-2-mm 直径的多缺损（n=6）。通过体内 micro-CT 在手术后 0、4、6 和 8 周评估骨再生，并在动物处死时通过体外 micro-CT 评估。通过微灌注动物脉管系统并用 microfil®灌注后扫描来量化缺损内的血管网络参数。
与 ZL 大鼠的结果相比，8-mm 直径的 ZDF 大鼠缺损的愈合动力学受损，新形成的骨体积（p<0.01）和表面积（p<0.01）显著减少，手术后 8 周。6-4-2-mm 直径的缺损表现出骨形成，这与大小或糖尿病状况无关。与 ZL 大鼠相比，在 ZDF 大鼠中，所有大小的缺损中血管体积和表面积均显著减少（p<0.05）。
本研究提供了证据表明，T2DM 会损害临界大小颅骨缺损中的骨形成，并显著减少所有缺陷中的血管生成，而与测试的缺陷大小无关。
