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Bone structure and B‐cell populations, crippled by obesity, are partially rescued by brief daily exposure to low‐magnitude mechanical signals
Author(s) -
Chan M. Ete,
Adler Benjamin J.,
Green Danielle E.,
Rubin Clinton T.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.12-209841
Subject(s) - bone marrow , osteoimmunology , immune system , haematopoiesis , stem cell , medicine , endocrinology , b cell , myeloid , biology , microbiology and biotechnology , immunology , receptor , antibody , activator (genetics) , rankl
Deterioration of the immune and skeletal systems, each of which parallel obesity, reflects a fragile interrelationship between adiposity and osteoimmunology. Using a murine model of diet‐induced obesity, this study investigated the ability of mechanical signals to protect the skeletal‐immune systems at the tissue, cellular, and molecular level. A long‐term (7 mo) high‐fat diet increased total adiposity (+62%), accelerated age‐related loss of trabecular bone (–61%), and markedly reduced B‐cell number in the marrow (–52%) and blood (–36%) compared to mice fed a regular diet. In the final 4 mo of the protocol, the application of low‐magnitude mechanical signals (0.2 g at 90 Hz, 15 min/d, 5 d/wk) restored both bone structure and B cells to those levels measured in control mice fed a regular diet. These phenotypic outcomes were achieved, in part, by reductions in osteoclastic activity and a biasing of hematopoietic stem cell differentiation toward the lymphoid B‐cell lineage and away from a myeloid fate. These results emphasize that obesity undermines both the skeletal and immune systems, yet brief exposure to mechanical signals, perhaps as a surrogate to the salutary influence of exercise, diminishes the consequences of diabetes and obesity, restoring bone structure and normalizing B‐cell populations by biasing of the fate of stem cells through mechanosensitive pathways.—Chan, M. E., Adler, B. J., Green, D. E., Rubin, C. T. Bone structure and B‐cell populations, crippled by obesity, are partially rescued by brief daily exposure to low‐magnitude mechanical signals. FASEB J. 26, 4855–4863 (2012). www.fasebj.org