Bone structure and B-cell populations, crippled by obesity, are partially rescued by brief daily exposure to low-magnitude mechanical signals.
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.
Department of Biomedical Engineering, Stony Brook University, Stony Brook, New York 11794-5281, USA.
M Ete
ME
Chan
Benjamin J
BJ
Adler
Danielle E
DE
Green
Clinton T
CT
Rubin
D000135:Acid Phosphatase / Q000235:genetics / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D001835:Body Weight / Q000502:physiology; D001854:Bone Marrow Cells / Q000378:metabolism; D001862:Bone Resorption / Q000209:etiology / Q000378:metabolism; D001842:Bone and Bones / Q000378:metabolism* / Q000473:pathology; D059305:Diet, High-Fat / Q000009:adverse effects; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015870:Gene Expression; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D050778:NFATC Transcription Factors / Q000235:genetics; D009765:Obesity / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D051757:PAX5 Transcription Factor / Q000235:genetics; D047495:PPAR gamma / Q000235:genetics; D010805:Physical Conditioning, Animal / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071681:Tartrate-Resistant Acid Phosphatase; D055114:X-Ray Microtomography
D007527:Isoenzymes; D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; D051757:PAX5 Transcription Factor; D047495:PPAR gamma; C497282:Pax5 protein, mouse; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase