Muscle loss is an important feature that occurs in multiple pathologies including osteoarthritis (OA), chronic obstructive pulmonary disease (COPD) and type II diabetes (T2D). Despite differences in pathogenesis and disease-related complications, there are reasons to believe that some fundamental underlying mechanisms are inherent to the muscle wasting process, irrespective of the pathology. Recent evidence shows that inflammation, either local or systemic, contributes to the modulation of muscle mass and/or muscle strength, via an altered molecular profile in muscle tissue. However, it remains ambiguous to which extent and via which mechanisms inflammatory signaling affects muscle mass in disease. Therefore, the objective of the present review is to discuss the role of inflammation on skeletal muscle anabolism, catabolism and functionality in three pathologies that are characterized by an eventual loss in muscle mass (and muscle strength), i.e. OA, COPD and T2D. In OA and COPD, most rodent models confirmed that systemic (COPD) or muscle (OA) inflammation directly induces muscle loss or muscle dysfunctionality. However, in a patient population, the association between inflammation and muscular maladaptations are more ambiguous. For example, in T2D patients, systemic inflammation is associated with muscle loss whereas in OA patients this link has not consistently been established. T2D rodent models revealed that increased levels of advanced glycation end-products (AGEs) and a decreased mTORC1 activation play a key role in muscle atrophy, but it remains to be elucidated whether AGEs and mTORC1 are interconnected and contribute to muscle loss in T2D patients. Generally, if any, associations between inflammation and muscle are mainly based on observational and cross-sectional data. There is definitely a need for longitudinal evidence through well-powered randomized control trials that take into account confounders such as age, disease-phenotypes, comorbidities, physical (in) activity etc. This will allow to improve our understanding of the complex interaction between inflammatory signaling and muscle mass loss and hence contribute to the development of therapeutic strategies to combat muscle wasting in these diseases.

中文翻译：

---

炎症信号是否参与与疾病相关的肌肉消瘦？来自骨关节炎，慢性阻塞性肺疾病和II型糖尿病的证据。

肌肉丢失是多种疾病的重要特征，包括骨关节炎（OA），慢性阻塞性肺疾病（COPD）和II型糖尿病（T2D）。尽管在发病机理和与疾病相关的并发症方面存在差异，但仍有理由相信，肌肉消瘦过程固有的一些基本潜在机制与病理无关。最近的证据表明，局部或全身性炎症通过改变肌肉组织中的分子分布来促进肌肉质量和/或肌肉力量的调节。然而，它在何种程度上和通过哪种机制影响炎症信号在疾病中的肌肉质量方面仍然不清楚。因此，本综述的目的是讨论炎症在骨骼肌合成代谢中的作用，三种病理学中的分解代谢和功能性，其最终特征是肌肉质量（和肌肉力量）的丧失，即OA，COPD和T2D。在OA和COPD中，大多数啮齿动物模型证实全身（COPD）或肌肉（OA）炎症直接导致肌肉损失或肌肉功能障碍。然而，在患者人群中，炎症和肌肉适应不良之间的关联更加模糊。例如，在T2D患者中，全身性炎症与肌肉损失有关，而在OA患者中，这种联系尚未得到确定。T2D啮齿动物模型显示，晚期糖基化终产物（AGEs）的水平升高和mTORC1激活的降低在肌肉萎缩中起关键作用，但尚需阐明AGEs和mTORC1是否相互连接并有助于T2D患者的肌肉丢失。通常，如果有的话，炎症和肌肉之间的关联主要基于观察和横截面数据。通过功能强大的随机对照试验，肯定需要纵向证据，其中要考虑混杂因素，例如年龄，疾病表型，合并症，身体（活动）活动等。这将有助于增进我们对炎症之间复杂相互作用的理解。信号转导和肌肉质量损失，因此有助于在这些疾病中对抗肌肉萎缩的治疗策略的发展。