Department of Orthopedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
Department of Orthopedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
Semin Cell Dev Biol. 2022 Mar;123:48-56. doi: 10.1016/j.semcdb.2021.05.001. Epub 2021 May 13.
Although the functions of the peripheral nervous system in whole body homeostasis and sensation have been understood for many years, recent investigation has uncovered new roles for innervation in the musculoskeletal system. This review centers on advances regarding the function of nerves in the development and repair of two connected tissues: tendon and bone. Innervation in healthy tendons is generally confined to the tendon sheaths, and tendon-bone attachment units are typically aneural. In contrast to tendon, bone is an innervated and vascularized structure. Historically, the function of abundant peripheral nerves in bone has been limited to pain and some non-painful sensory perception in disease and injury. Indeed, much of our understanding of peripheral nerves in tendons, bones, and entheses is limited to the source and type of innervation in healthy and injured tissues. However, more recent studies have made important observations regarding the appearance, type, and innervation patterns of nerves during embryonic and postnatal development and in response to injury, which suggest a more expansive role for peripheral nerves in the formation of musculoskeletal tissues. Indeed, tendons and bones develop in a close spatiotemporal relationship in the embryonic mesoderm. Models of limb denervation have shed light on the importance of sensory innervation in bone and to a lesser extent, tendon development, and more recent work has unraveled key nerve signaling pathways. Furthermore, loss of sensory innervation also impairs healing of bone fractures and may contribute to chronic tendinopathy. However, more study is required to translate our knowledge of peripheral nerves to therapeutic strategies to combat bone and tendon diseases.
尽管外周神经系统在全身稳态和感觉中的功能已被人们了解多年，但最近的研究揭示了神经在肌肉骨骼系统中的新作用。这篇综述主要关注神经在两种相关组织（肌腱和骨骼）的发育和修复中的功能的最新进展。健康肌腱中的神经支配通常局限于肌腱鞘，肌腱-骨附着部位通常是无神经支配的。与肌腱不同，骨骼是一个有神经支配和血管化的结构。从历史上看，丰富的外周神经在骨骼中的功能仅限于疾病和损伤时的疼痛和一些非疼痛性感觉感知。事实上，我们对肌腱、骨骼和附着点中丰富的外周神经的理解很大程度上局限于健康和受伤组织中的神经来源和类型。然而，最近的研究对胚胎和出生后发育过程中以及受伤时神经的出现、类型和支配模式进行了重要观察，这表明外周神经在肌肉骨骼组织形成中可能发挥更广泛的作用。事实上，肌腱和骨骼在胚胎中胚层中以紧密的时空关系发育。肢体去神经支配模型揭示了感觉神经支配对骨骼发育的重要性，以及对肌腱发育的较小影响，最近的研究还揭示了关键的神经信号通路。此外，感觉神经支配的丧失也会损害骨骼骨折的愈合，并可能导致慢性肌腱病。然而，需要更多的研究将我们对外周神经的了解转化为治疗策略，以对抗骨骼和肌腱疾病。
