Molecular Biology of Bones and Teeth Section, Craniofacial and Skeletal Diseases Branch, National Institutes of Dental and Craniofacial Research, National Institutes of Health, Maryland, USA.
Scand J Med Sci Sports. 2009 Aug;19(4):536-46. doi: 10.1111/j.1600-0838.2009.00909.x. Epub 2009 Apr 13.
We present a detailed comparison of ectopic ossification (EO) found in tendons of biglycan (Bgn), fibromodulin (Fmod) single and double Bgn/Fmod-deficient (DKO) mice with aging. At 3 months, Fmod KO, Bgn KO and DKO displayed torn cruciate ligaments and EO in their quadriceps tendon, menisci and cruciate and patellar ligaments. The phenotype was the least severe in the Fmod KO, intermediate in the Bgn KO and the most severe in the DKO. This condition progressed with age in all three mouse strains and resulted in the development of large supernumerary sesmoid bones. To determine the role of exercise in the extent of EO, we subjected normal and DKO mice to a treadmill exercise 3 days a week for 4 weeks. In contrast to previous findings using more rigorous exercise regimes, the EO in moderately exercised DKO was decreased compared with unexercised DKO mice. Finally, DKO and Bgn KO mice tested using a rotarod showed a reduced ability to maintain their grip on a rotating cylinder compared with wild-type controls. In summary, we show (1) a detailed description of EO formed by Bgn, Fmod or combined depletion, (2) the role of exercise in modulating EO and (3) that Bgn and Fmod are critical in controlling motor function.
我们对 BIGLYCAN（BGN）、纤维调节素（Fmod）单基因敲除和双基因敲除（DKO）小鼠肌腱中的异位骨化（EO）与年龄的关系进行了详细比较。在 3 个月时，Fmod KO、Bgn KO 和 DKO 小鼠的十字韧带撕裂，股四头肌肌腱、半月板、十字韧带和髌韧带出现 EO。Fmod KO 小鼠的表型最不严重，Bgn KO 小鼠的表型介于中间，DKO 小鼠的表型最严重。在所有三种小鼠品系中，这种情况随年龄增长而逐渐加重，并导致大量额外的籽骨形成。为了确定运动在 EO 程度中的作用，我们让正常和 DKO 小鼠每周进行 3 天的跑步机运动，持续 4 周。与以前使用更严格的运动方案的发现相反，与未运动的 DKO 小鼠相比，适度运动的 DKO 中的 EO 减少。最后，与野生型对照组相比，在转棒上测试的 DKO 和 Bgn KO 小鼠显示出维持其在旋转圆柱体上的抓握能力降低。总之，我们展示了（1）BGN、Fmod 或联合缺失形成的 EO 的详细描述，（2）运动在调节 EO 中的作用，（3）BGN 和 Fmod 在控制运动功能中的重要性。
