The rotator cuff us a sleeve of four muscles that attach the proximal humerus to the scapula. Its primary role is to initiation of shoulder movement and control of the arm position in space. Rotator cuff tears (RCT) are increasingly common in the aging population, with some studies showing that up to 20% of the population greater than 50 years of age has a symptomatic RCT. Patients will symptomatic RCT have difficulties raising their arms and many of their daily activities are impaired as a result. Our VA patients are an advanced aging population, compared to general population in U.S. With the aging of our Veteran population, RCT is becoming a more and more important health issue for the VA patients. The development of muscle fibrosis and fatty infiltration (FI) are critical factors that determine the clinical outcome of patients with tis injury. It has been demonstrated that the amount of FI in rotator cuff muscles correlate with poor clinical results. There is no effective strategies currently exist to treat this pathologic change once it occurs. Recent works from multiple groups have suggested that a population of muscle progenitor cells, named fibro-adipo progenitor cells (FAPs) are responsible for muscle fibrosis and FI after direct muscle injuries. However, the role of FAPs in rotator cuff muscle pathology has not been studied. The transforming growth factor beta (TGF?) and bone morphogenetic protein (BMP) signaling pathways have been reported to play critical roles in regulating stem cell differentiation, including fibrogenesis and adipogenesis. However, their role in regulating FAPs differentiation in rotator cuff muscle fibrosis and FI remains unknown. Better understanding of the role of these pathways in rotator cuff muscle fibrosis and fatty infiltration may lead to novel pharmacological treatment to prevent or reserve muscle pathology after RCT, thus to improve the clinical outcomes for our effect Veterans.
Rotator cuff tears are increasingly common in the aging population. Patients with a nonfunctional rotator cuff are difficult to elevate the arm to perform activities of daily living. ith the aging of our Veteran population, rotator cuff tears are becoming a more and more important health issue for the VA patients. The development of muscle fibrosis and fatty infiltration (FI) ar critical factors that determine the clinical outcome of patients with this injury. However, there i no effective treatment for this disease at this time due to our limited understanding of the mechanisms. Successful achievement of this project will define the cellular source and important molecular pathways responsible rotator cuff muscle fibrosis and FI. Results from this study may lead to new therapeutic approaches to treat this disease. Therefore, our proposal has particular significance for the VA population.
|Davies, Michael R; Lee, Lawrence; Feeley, Brian T et al. (2017) Lysophosphatidic acid-induced RhoA signaling and prolonged macrophage infiltration worsens fibrosis and fatty infiltration following rotator cuff tears. J Orthop Res 35:1539-1547|
|Davies, Michael R; Liu, Xuhui; Lee, Lawrence et al. (2016) TGF-? Small Molecule Inhibitor SB431542 Reduces Rotator Cuff Muscle Fibrosis and Fatty Infiltration By Promoting Fibro/Adipogenic Progenitor Apoptosis. PLoS One 11:e0155486|
|Liu, Xuhui; Ning, Anne Y; Chang, Nai Chen et al. (2016) Investigating the cellular origin of rotator cuff muscle fatty infiltration and fibrosis after injury. Muscles Ligaments Tendons J 6:6-15|