NF-KB activity functions in primary pericytes in a cell- and non-cell-autonomous manner to affect myotube formation.
BACKGROUND
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 C2 C12 myoblasts under differentiation conditions, and HPP fusion to myotubes was measured. We also co-cultured HPPs with C2 C12 myoblasts and measured proliferation and myotube formation.


RESULTS
Inhibition of NF-kB activity increased HPP fusion to C2 C12 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.
Department of Kinesiology, University of Massachusetts Amherst, 300 Massachusetts Avenue, Amherst, Massachusetts 01003, USA. robhyldahl@byu.edu
Robert D
RD
Hyldahl
Lawrence M
LM
Schwartz
Priscilla M
PM
Clarkson
D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D006801:Humans; D024510:Muscle Development / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000502:physiology*; D032446:Myoblasts / Q000166:cytology / Q000502:physiology*; D052002:NF-kappa B p50 Subunit / Q000502:physiology*; D020286:Pericytes / Q000378:metabolism / Q000502:physiology*; D012038:Regeneration / Q000502:physiology*
D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human