Osteoclastogenesis by bone marrow-derived macrophages is enhanced in obese mice.
Obesity induces a low-grade systemic chronic inflammatory condition for which macrophages are responsible. We hypothesized that obesity affects osteoclastogenesis by acting on bone marrow-derived macrophages (BMM). Male mice were fed a high-fat diet (45% of energy) or a standard diet (10% of energy) for 13 wk. We found that the density of the femurs of obese mice was significantly lower than that of the femurs of lean mice. Osteoclastogenesis was enhanced in the BMM from obese mice. Lower levels of interleukin (IL)-10 were generated by the BMM from obese mice than by those from lean mice upon stimulation of receptor activator of nuclear factor-kappaB ligand. Neutralization of IL-10 in the BMM from obese mice was not as effective in increasing osteoclast (OC) formation as that in those from lean mice. Exogenous IL-10 inhibited OC formation more strongly in the BMM from obese mice than those from lean mice. The elevated level of OC formation in the BMM from obese mice may thus be due to in part to the lower level of IL-10, a negative regulator of osteoclastogenesis. Our results suggest that obesity is associated with bone loss via enhanced osteoclastogenesis due to reduced IL-10 production by the BMM from obese mice.
Kyung
Tae-Wook
TW
Department of Biological Sciences (BK21 Program) and the Immunomodulation Research Center, University of Ulsan, Ulsan 680-749, Korea.
Lee
Ji-Eun
JE
Phan
Tien Van
TV
Yu
Rina
R
Choi
Hye-Seon
HS
D000818:Animals; D015519:Bone Density / Q000502:physiology*; D001862:Bone Resorption / Q000209:etiology / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage*; D016753:Interleukin-10 / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000150:complications / Q000378:metabolism*; D010010:Osteoclasts / Q000502:physiology*; D053245:RANK Ligand / Q000494:pharmacology; D013047:Specific Pathogen-Free Organisms
D004041:Dietary Fats; D053245:RANK Ligand; D016753:Interleukin-10