Facioscapulohumeral muscular dystrophy (FSHD) is a genetic disease associated with ectopic expression of the DUX4 gene in skeletal muscle. Muscle degeneration in FSHD is accompanied by muscle tissue replacement with fat and connective tissue. Expression of DUX4 in myoblasts stimulates mesenchymal stem cells (MSC) migration via the CXCR4‐CXCL12 axis. MSCs participate in adipose and connective tissue formation and can contribute to fibrosis. Here we studied the interaction between myoblasts and MSCs and the consequences of this interaction in the FSHD context. We used cell motility assays and coculture of MSCs with myoblasts to study their mutual effects on cell migration, differentiation, proliferation, and extracellular matrix formation. The growth medium conditioned by FSHD myoblasts stimulated MSCs migration 1.6‐fold (p < 0.04) compared to nonconditioned medium. Blocking the CXCL12‐CXCR4 axis with the CXCR4 inhibitor (AMD3100) or neutralizing antibodies to CXCL12 abolished this effect. FSHD myoblasts stimulated MSC proliferation 1.5−2 times (p < 0.05) compared to control myoblasts, while the presence of MSCs impaired myoblast differentiation. Under inflammatory conditions, medium conditioned by FSHD myoblasts stimulated collagen secretion by MSCs 2.2‐fold as compared to the nonconditioned medium, p < 0.03. FSHD myoblasts attract MSCs via the CXCL12‐CXCR4 axis, stimulate MSC proliferation and collagen secretion by MSCs. Interaction between MSCs and FSHD myoblasts accounts for several important aspects of FSHD pathophysiology. The CXCL12‐CXCR4 axis may serve as a potential target to improve the state of the diseased muscles.
Neuromuscular Disorders 31 (2021) S47-S162 between baseline and follow up did not correlate with the change in clinical outcome measures. Fifteen patients had a deterioration of FVC of more than 10% predicted, the other 77 patients showed no significant change in FVC% predicted. This subgroup of 15 patients had higher FSHD severity scores, lower MMT sum scores and lower MFM scores at baseline. They more frequently developed spinal and thorax deformities at follow up and had a larger decline in MFM scores between baseline and follow up. During 5year follow up, respiratory function deteriorates slowly and a subgroup of FSHD patients had a more rapid deterioration. These patients were more severely affected at baseline, had spinal and thorax deformities and showed a relatively fast decline in motor function.
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