含有镁的可生物降解整形外科植入物已被用于骨折修复，并且疗显著。然而，这些植入物改善骨折愈合的潜在机制仍然难以琢磨。最近香港中文大学的郑玉峰教授课题组，使用金属镁制作的髓内针制备了一种有助于骨骼修复促进骨愈合的骨植入物。并且探究了金属镁与神经之间的关联。其将含有超纯镁的髓内针向大鼠完整的股骨远端进行髓内植入后，在周围皮质部位形成了丰富的新骨。这种反应伴随着股骨外周皮质和同侧背根神经节（DRG）中神经元降钙素基因相关多肽-α（CGRP）的大量增加。手术切除骨膜，感觉神经或辣椒素去神经降低在体内的CGRP受体编码基因的CALCRL或过表达或者抑制逆转了在该模型中观察到的镁诱导的成骨作用。然而，这些基因的过表达增强了镁诱导的成骨作用。进一步发现，细胞外镁的升高会诱导镁转运蛋白1（MAGT1）依赖性和瞬时受体电位阳离子通道，亚家族M，成员7（TRPM7）依赖性镁进入，以及细胞内三磷酸腺苷（ATP）的增加和分离的大鼠DRG神经元中的突触末梢小泡的积累。在分离的大鼠骨膜来源干细胞中，CGRP诱导cAMP响应元件结合蛋白1（CREB1）和SP7（也称为osterix）的CALCRL和RAMP1依赖性激活，从而增强这些干细胞的成骨分化。此外，开发了一种创新的，含镁的髓内钉有助于卵巢切除术诱发的骨质疏松大鼠股骨骨折的修复。综上所述，这些发现揭示了镁在促进CGRP介导的成骨分化中的作用尚未确定，这表明该离子在整形外科领域具有治疗潜力。

Biodegradable orthopaedic implants containing magnesium have been used for fracture repair and have been significantly therapeutic.However, the underlying mechanism by which these implants improve fracture healing remains elusive.Recently, a team led by Yufeng Cheng of the Chinese University of Hong Kong used magnesium to make an intramedullary needle to prepare a bone implant that can help repair and promote bone healing.And explored the link between magnesium and nerves.After intramedullary insertion of an intramedullary needle containing ultrapure magnesium into the intact distal femur of rats, abundant new bone was formed in the surrounding cortex.This response was accompanied by a significant increase in neuronal calcitonin gene-related polypeptide (CGRP) in the peripheral femoral cortex and ipsilateral dorsal root ganglion (DRG).Surgical excision of periosteum and sensory nerve or capsaicin demulsification of the CALCRL or overexpression or inhibition of the CGRP receptor-encoding gene in vivo reversed the magnesium-induced osteogenesis observed in this model.However, overexpression of these genes enhanced magnesium – induced osteogenesis.It was further found that the increase in extracellular magnesium induced magT1-dependent and transient receptor-potential cation channels, subfamily M, member 7 (TRPM7-dependent magnesium entry, intracellular adenosine triphosphate (ATP) increase, and the accumulation of synaptic vesicles in isolated rat DRG neurons.CGRP induces CALCRL and RAMP1 dependent activation of cAMP responsive element binding protein 1 (CREB1) and SP7 (also known as Osterix) in isolated rat periosted-derived stem cells, thereby enhancing osteogenic differentiation of these stem cells.In addition, an innovative, magnesium-containing intramedullary nail was developed to help repair femur fractures in ovariectomized rats with osteoporosis.Taken together, these findings reveal that the role of magnesium in promoting CGRP-mediated osteogenic differentiation has not been determined, indicating that the ion has therapeutic potential in the field of plastic surgery.

DOI：10.1038 / nm.4162

刘香笈