Norris Alessandra M, Palzkill Victoria R, Appu Ambili B, Fierman Kiara E, Noble Christian D, Ryan Terence E, Kopinke Daniel
University of Florida, Department of Pharmacology and Therapeutics, Myology Institute, Gainesville, FL, USA.
University of Florida, Department of Applied Physiology and Kinesiology, Myology Institute, Gainesville, FL, USA.
Cell Rep. 2025 Aug 26;44(8):116021. doi: 10.1016/j.celrep.2025.116021. Epub 2025 Jul 15.
With age and disease, skeletal muscle is progressively lost and replaced by fibrotic scar and intramuscular adipose tissue (IMAT). While strongly correlated, it remains unclear whether IMAT has a functional impact on muscle. In the present study, we evaluated the impact of IMAT on muscle regeneration by creating a mouse model where the cellular origin of IMAT, fibro/adipogenic progenitors (FAPs), is prevented from differentiating into adipocytes (mFATBLOCK model). We found that blocking IMAT after an adipogenic injury allowed muscle to regenerate more efficiently, resulting in enhanced functional recovery. Our data explain why acute muscle injuries featuring IMAT infiltration, such as rotator cuff tears and acute denervation injuries, exhibit poor regeneration and lead to a loss of muscle function. It also demonstrates the therapeutic importance of preventing IMAT formation in acute injuries in order to maximize regeneration and minimize loss in muscle mass and function.
随着年龄增长和疾病发生，骨骼肌会逐渐流失，并被纤维化瘢痕和肌内脂肪组织（IMAT）所取代。虽然两者密切相关，但IMAT是否对肌肉有功能影响仍不清楚。在本研究中，我们通过创建一个小鼠模型来评估IMAT对肌肉再生的影响，在该模型中，IMAT的细胞起源，即纤维/脂肪生成祖细胞（FAPs），被阻止分化为脂肪细胞（mFATBLOCK模型）。我们发现，在脂肪生成损伤后阻断IMAT可使肌肉更有效地再生，从而增强功能恢复。我们的数据解释了为什么以IMAT浸润为特征的急性肌肉损伤，如肩袖撕裂和急性去神经损伤，会表现出较差的再生能力并导致肌肉功能丧失。它还证明了在急性损伤中防止IMAT形成对于最大化再生以及最小化肌肉质量和功能损失的治疗重要性。
