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NF-KB activity functions in primary pericytes in a cell- and non-cell-autonomous manner to affect myotube formation


Correspondence to: R. D. Hyldahl; E-mail:


Introduction: Skeletal muscle regeneration following damage relies on proliferation and differentiation of muscle precursor cells (MPCs). We recently observed increased NF-kB activity in vascular-associated muscle resident pericytes following muscle damage in humans. We determined how altered NF-kB activity in human primary pericytes (HPPs) affects their myogenic differentiation (cell-autonomous effects), as well as proliferation and differentiation of co-cultured MPCs (non–cell-autonomous effects). Methods: HPPs were transfected with vectors that increased or decreased NF-kB activity. Transfected HPPs were co-cultured with C2C12 myoblasts under differentiation conditions, and HPP fusion to myotubes was measured. We also co-cultured HPPs with C2C12 myoblasts and measured proliferation and myotube formation. Results: Inhibition of NF-kB activity increased HPP fusion to C2C12 myotubes. Moreover, enhanced NF-kB activity in HPPs suppressed differentiation and enhanced proliferation of co-cultured myoblasts. Conclusions: NF-kB activity acts cell-autonomously to inhibit HPP myogenic differentiation and non–cell-autonomously to promote MPC proliferation and suppress MPC differentiation in vitro. Muscle Nerve, 2013