University of Michigan School of Dentistry, Ann Arbor, MI.
Vanderbilt Center for Bone Biology.
J Musculoskelet Neuronal Interact. 2020 Mar 3;20(1):149-159.
Conditional () mice have previously been used as a model of heterotopic ossification (HO). However, HO formation in this model can be highly variable, and it is unclear which methods reliably induce HO. Hence, these studies report validated methods for reproducibly inducing HO in mice.
Varying doses of Adex-cre and cardiotoxin (CTX) were injected into the calf muscles of 9, 14, or 28-day-old or mice. HO was measured by planar radiography or microCT at 14-28 days post-injury.
In 9-day-old or mice, single injections of 10 PFU Adex-cre and 0.3 μg of CTX were sufficient to induce extensive HO within 14 days post-injury. In 28-day-old mice, the doses were increased to 5 x 10 PFU Adex-cre and 3.0 μg of CTX to achieve similar consistency, but at a slower rate versus younger mice. Using a crush injury, instead of CTX, also provided consistent induction of HO. Finally, the Type 1 BMPR inhibitor, DMH1, significantly reduced HO formation in 28-day-old mice.
These data illustrate multiple methods for reliable induction of localized HO in the mouse that can serve as a starting point for new laboratories utilizing this model.
条件性 （）小鼠先前被用作异位骨化 (HO) 的模型。然而，该模型中的 HO 形成具有高度可变性，并且不清楚哪种方法能够可靠地诱导 HO。因此，这些研究报告了在 小鼠中可靠诱导 HO 的验证方法。
在 9、14 或 28 日龄的 或 小鼠的小腿肌肉中注射不同剂量的 Adex-cre 和心脏毒素 (CTX)。在损伤后 14-28 天通过平面射线照相术或 microCT 测量 HO。
在 9 日龄的 或 小鼠中，单次注射 10 PFU Adex-cre 和 0.3 μg CTX 足以在损伤后 14 天内诱导广泛的 HO。在 28 日龄的小鼠中，剂量增加到 5×10 PFU Adex-cre 和 3.0 μg CTX 以达到类似的一致性，但速度比年轻小鼠慢。使用挤压伤而不是 CTX 也可以提供一致的 HO 诱导。最后，I 型 BMPR 抑制剂 DMH1 显著减少了 28 日龄 小鼠中的 HO 形成。
这些数据说明了在小鼠中可靠诱导局部 HO 的多种方法，可为利用该模型的新实验室提供起点。
