Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX 77030, United States.
Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX 77030, United States; Department of Pediatrics - Section Hematology/Oncology, Baylor College of Medicine, Houston, TX 77030, United States; Department of Orthopedic Surgery, Baylor College of Medicine, Houston, TX 77030, United States.
Bone. 2018 Apr;109:22-27. doi: 10.1016/j.bone.2017.07.016. Epub 2017 Jul 15.
Heterotopic ossification (HO), or de novo bone formation in soft tissue, is often observed following traumatic injury. Recent studies suggest that peripheral nerves may play a key functional role in this process. The results supporting a neurological basis for HO are examined in this article. Evidence supports the fact that BMPs released from bone matrix possess the capacity to induce HO. However, the process cannot be recapitulated using recombinant proteins without extremely high doses suggesting other components are required for this process. Study of injuries that increase risk for HO, i.e. amputation, hip replacement, elbow fracture, burn, and CNS injury suggests that a likely candidate is traumatic injury of adjacent peripheral nerves. Recent studies suggest neuroinflammation may play a key functional role, by its ability to open the blood-nerve barrier (BNB). Barrier opening is characterized by a change in permeability and is experimentally assessed by the ability of Evans blue dye to enter the endoneurium of peripheral nerves. A combination of BMP and barrier opening is required to activate bone progenitors in the endoneurial compartment. This process is referred to as "neurogenic HO".
异位骨化(HO),即在软组织中形成新骨,常发生于创伤后。最近的研究表明,周围神经可能在这一过程中发挥关键作用。本文探讨了支持 HO 具有神经基础的研究结果。有证据表明,骨基质中释放的 BMP 具有诱导 HO 的能力。然而,如果不使用极高剂量的重组蛋白,这一过程就无法重现,这表明还需要其他成分来完成这一过程。对增加 HO 风险的损伤(如截肢、髋关节置换、肘部骨折、烧伤和 CNS 损伤)的研究表明,相邻周围神经的创伤可能是一个潜在的候选因素。最近的研究表明,神经炎症可能通过其打开血-神经屏障(BNB)的能力发挥关键作用。屏障打开的特征是通透性的变化,通过 Evans 蓝染料进入周围神经的神经内膜的能力来实验性评估。BMP 和屏障打开的结合是激活神经内膜间隙中骨祖细胞所必需的。这一过程被称为“神经源性 HO”。