title: TNFalpha receptor knockout in mice reduces adverse effects of magnesium deficiency on bone.
abstract: Epidemiologic studies have linked low dietary magnesium (Mg) intake to osteoporosis. Dietary Mg restriction in animal models has demonstrated a decrease in bone mass and an increase in skeletal fragility. The exact mechanism for the decrease in bone mass is not clear but a decrease in osteoblast number and an increase in osteoclast number (Oc.No/B.Pm) suggests an uncoupling of bone formation and bone resorption favoring skeletal loss. Mg depletion results in an increase in inflammatory cytokines, which could explain the increase in bone resorption. We have previously demonstrated an increase in TNFalpha in bone from Mg deficient rodents. Here we report results of a 3 week study of a low magnesium (LM) diet and normal Mg diet in 35-day-old TNFalpha receptor knockout mice (TNF-r-KO) versus wild type (WT) control mice. Our results indicated that a LM diet resulted in a greater increase in Oc.No/B.Pm in the WT mice, with a trend toward greater eroded bone perimeter, as compared to TNF-r-KO. These findings suggest that TNFalpha may play a role in Mg deficiency-induced bone loss.
authors.affiliation: Keck School of Medicine and Orthopaedic Hospital, University of Sourthern California, Los Angeles, CA, 90033, USA. rrude60075@aol.com
authors.forename: Robert K
authors.initials: RK
authors.lastname: Rude
authors.forename: Livia
authors.initials: L
authors.lastname: Wei
authors.forename: H James
authors.initials: HJ
authors.lastname: Norton
authors.forename: Shi Shou
authors.initials: SS
authors.lastname: Lu
authors.forename: David W
authors.initials: DW
authors.lastname: Dempster
authors.forename: Helen E
authors.initials: HE
authors.lastname: Gruber
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000209:etiology*; D004195:Disease Models, Animal; D005269:Femur / Q000378:metabolism / Q000473:pathology; D008274:Magnesium / Q000378:metabolism / Q000494:pharmacology*; D008275:Magnesium Deficiency / Q000150:complications* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D008274:Magnesium