Yin Kai, Zhang Chengmin, Deng Zihan, Wei Xiaoyu, Xiang Tingwen, Yang Chuan, Chen Can, Chen Yueqi, Luo Fei
Department of Orthopedics, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, People's Republic of China.
Department of Biomedical Materials Science, Third Military Medical University (Army Medical University), Chongqing, People's Republic of China.
FASEB J. 2024 Dec 13;38(24):e70234. doi: 10.1096/fj.202400381R.
As a common clinical manifestation, muscle weakness is prevalent in people with mobility disorders. Further studies of muscle weakness have found that patients with muscle weakness present with persistent muscle inflammation, loss of muscle fibers, fat infiltration, and interstitial fibrosis. Therefore, we propose the concept of muscle microenvironment homeostasis, which explains the abnormal pathological changes in muscles through the imbalance of muscle microenvironment homeostasis. And we identified an interstitial progenitor cell FAP during the transition from normal muscle microenvironment homeostasis to muscle microenvironment imbalance caused by muscle damage diseases. As a kind of pluripotent stem cell, FAPs do not participate in myogenic differentiation, but can differentiate into fibroblasts, adipocytes, osteoblasts, and chondrocytes. As a kind of mesenchymal progenitor cell, it is involved in the generation of extracellular matrix, regulate muscle regeneration, and maintain neuromuscular junction. However, the muscle microenvironment is disrupted by the causative factors, and the abnormal activities of FAPs eventually contribute to the complex pathological changes in muscles. Targeting the mechanisms of these muscle pathological changes, we have identified appropriate signaling targets for FAPs to improve and even treat muscle damage diseases. In this review, we propose the construction of muscle microenvironmental homeostasis and find the key cells that cause pathological changes in muscle after homeostasis is broken. By studying the mechanism of abnormal differentiation and apoptosis of FAPs, we found a strategy to inhibit the abnormal pathological changes in muscle damage diseases and improve muscle regeneration.
作为一种常见的临床表现，肌肉无力在行动障碍患者中普遍存在。对肌肉无力的进一步研究发现，肌肉无力患者存在持续性肌肉炎症、肌纤维丢失、脂肪浸润和间质纤维化。因此，我们提出了肌肉微环境稳态的概念，通过肌肉微环境稳态失衡来解释肌肉中的异常病理变化。并且我们在由肌肉损伤疾病导致的从正常肌肉微环境稳态向肌肉微环境失衡转变过程中鉴定出一种间质祖细胞FAP。作为一种多能干细胞，FAPs不参与肌源性分化，但可分化为成纤维细胞、脂肪细胞、成骨细胞和软骨细胞。作为一种间充质祖细胞，它参与细胞外基质的生成，调节肌肉再生，并维持神经肌肉接头。然而，致病因素破坏了肌肉微环境，FAPs的异常活动最终导致肌肉出现复杂的病理变化。针对这些肌肉病理变化的机制，我们已经确定了FAPs的合适信号靶点，以改善甚至治疗肌肉损伤疾病。在本综述中，我们提出构建肌肉微环境稳态，并找出稳态打破后导致肌肉病理变化的关键细胞。通过研究FAPs异常分化和凋亡的机制，我们找到了一种抑制肌肉损伤疾病异常病理变化并改善肌肉再生的策略。
