Muscle-bone interactions: From experimental models to the clinic? A critical update
Muscle-bone interactions: From experimental models to the clinic? A critical update
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DOI：
10.1016/j.mce.2015.10.017
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发表时间：
2016-09-05
影响因子：
4.1
通讯作者：
Jardi, Ferran
中科院分区：
文献类型：
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作者：
Laurent, Michael R.;Dubois, Vanessa;Jardi, Ferran
骨是由肌肉和重力形成的生物力学组织。骨骼和肌肉同时衰退和功能障碍（骨减少症或肌肉-骨质疏松症）见于衰老、许多临床情况，包括中风或瘫痪后、神经肌肉营养不良、糖皮质激素过量、或与维生素D、生长激素/胰岛素样生长因子或性类固醇缺乏有关，以及航天飞行。在这些情况下，体育锻炼可能是有益的，但仍需要进一步的工作来将可接受的和有效的生物力学干预，如振动疗法从动物模型转化为人类。新的抗吸收和合成代谢疗法正在出现用于骨质疏松症以及用于肌肉减少症、癌症恶病质或肌肉消耗病症的药物，包括针对肌肉生长抑制素或IIA和IIB型激活素受体的抗体（例如比麦单抗）。理想情况下，增加肌肉质量会增加肌肉强度并恢复因废用而导致的骨质流失。然而，经典的观点认为，肌肉是单向主导骨通过机械负荷是过于简单化。事实上，最近的研究表明，神经元不仅对肌肉，而且对骨代谢、骨信号传导途径（如与肌肉生物学有关的核因子κ-B配体受体激活剂（RANKL））、影响骨的肌因子和可能的骨-肌肉通讯都有调节作用。此外，诱导孤立的肌细胞肥大的药理学策略可能不会转化为增加的肌肉力量，因为肌腱，结缔组织，神经元和能量代谢也需要适应。我们的目的是在这里严格审查关键肌肉骨骼分子通路参与机械调节和它们对骨-肌肉单位作为一个整体的影响，以及临床前和新出现的临床证据，关于肌肉减少症治疗骨质疏松症的影响，反之亦然。(C)2015爱思唯尔爱尔兰有限公司版权所有。
Bone is a biomechanical tissue shaped by forces from muscles and gravitation. Simultaneous bone and muscle decay and dysfunction (osteosarcopenia or sarco-osteoporosis) is seen in ageing, numerous clinical situations including after stroke or paralysis, in neuromuscular dystrophies, glucocorticoid excess, or in association with vitamin D, growth hormone/insulin like growth factor or sex steroid deficiency, as well as in spaceflight. Physical exercise may be beneficial in these situations, but further work is still needed to translate acceptable and effective biomechanical interventions like vibration therapy from animal models to humans. Novel antiresorptive and anabolic therapies are emerging for osteoporosis as well as drugs for sarcopenia, cancer cachexia or muscle wasting disorders, including antibodies against myostatin or activin receptor type IIA and IIB (e.g. bimagrumab). Ideally, increasing muscle mass would increase muscle strength and restore bone loss from disuse. However, the classical view that muscle is unidirectionally dominant over bone via mechanical loading is overly simplistic. Indeed, recent studies indicate a role for neuronal regulation of not only muscle but also bone metabolism, bone signaling pathways like receptor activator of nuclear factor kappa-B ligand (RANKL) implicated in muscle biology, myokines affecting bone and possible bone-to-muscle communication. Moreover, pharmacological strategies inducing isolated myocyte hypertrophy may not translate into increased muscle power because tendons, connective tissue, neurons and energy metabolism need to adapt as well. We aim here to critically review key musculoskeletal molecular pathways involved in mechanoregulation and their effect on the bone-muscle unit as a whole, as well as preclinical and emerging clinical evidence regarding the effects of sarcopenia therapies on osteoporosis and vice versa. (C) 2015 Elsevier Ireland Ltd. All rights reserved.