title: Loss of Bone and Wnt10b Expression in Male Type 1 Diabetic Mice Is Blocked by the Probiotic Lactobacillus reuteri.
abstract: Type 1 diabetes (T1D)-induced osteoporosis is characterized by a predominant suppression of osteoblast number and activity, as well as increased bone marrow adiposity but no change in osteoclast activity. The fundamental mechanisms and alternative anabolic treatments (with few side effects) for T1D bone loss remain undetermined. Recent studies by our laboratory and others indicate that probiotics can benefit bone health. Here, we demonstrate that Lactobacillus reuteri, a probiotic with anti-inflammatory and bone health properties, prevents T1D-induced bone loss and marrow adiposity in mice. We further found that L. reuteri treatment prevented the suppression of Wnt10b in T1D bone. Consistent with a role for attenuated bone Wnt10b expression in T1D osteoporosis, we observed that bone-specific Wnt10b transgenic mice are protected from T1D bone loss. To examine the mechanisms of this protection, we focused on TNF-α, a cytokine up-regulated in T1D that causes suppression of osteoblast Wnt10b expression in vitro. Addition of L. reuteri prevented TNF-α-mediated suppression of Wnt10b and osteoblast maturation markers. Taken together, our findings reveal a mechanism by which T1D causes bone loss and open new avenues for use of probiotics to benefit the bone.
authors.affiliation: Department of Physiology (J.Z., K.J.M., R.I., L.R.M.), Department of Molecular and Integrative Physiology (O.A.M.), Department of Microbiology and Molecular Genetics (R.A.B.), Department of Radiology (L.R.M.), and Biomedical Imaging Research Center (L.R.M.), Michigan State University, East Lansing, Michigan 48824.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Physiology (J.Z., K.J.M., R.I., L.R.M.), Department of Molecular and Integrative Physiology (O.A.M.), Department of Microbiology and Molecular Genetics (R.A.B.), Department of Radiology (L.R.M.), and Biomedical Imaging Research Center (L.R.M.), Michigan State University, East Lansing, Michigan 48824.
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Motyl
authors.affiliation: Department of Physiology (J.Z., K.J.M., R.I., L.R.M.), Department of Molecular and Integrative Physiology (O.A.M.), Department of Microbiology and Molecular Genetics (R.A.B.), Department of Radiology (L.R.M.), and Biomedical Imaging Research Center (L.R.M.), Michigan State University, East Lansing, Michigan 48824.
authors.forename: Regina
authors.initials: R
authors.lastname: Irwin
authors.affiliation: Department of Physiology (J.Z., K.J.M., R.I., L.R.M.), Department of Molecular and Integrative Physiology (O.A.M.), Department of Microbiology and Molecular Genetics (R.A.B.), Department of Radiology (L.R.M.), and Biomedical Imaging Research Center (L.R.M.), Michigan State University, East Lansing, Michigan 48824.
authors.forename: Ormond A
authors.initials: OA
authors.lastname: MacDougald
authors.affiliation: Department of Physiology (J.Z., K.J.M., R.I., L.R.M.), Department of Molecular and Integrative Physiology (O.A.M.), Department of Microbiology and Molecular Genetics (R.A.B.), Department of Radiology (L.R.M.), and Biomedical Imaging Research Center (L.R.M.), Michigan State University, East Lansing, Michigan 48824.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Britton
authors.affiliation: Department of Physiology (J.Z., K.J.M., R.I., L.R.M.), Department of Molecular and Integrative Physiology (O.A.M.), Department of Microbiology and Molecular Genetics (R.A.B.), Department of Radiology (L.R.M.), and Biomedical Imaging Research Center (L.R.M.), Michigan State University, East Lansing, Michigan 48824.
authors.forename: Laura R
authors.initials: LR
authors.lastname: McCabe
mesh_terms: D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000378:metabolism; D052200:Limosilactobacillus reuteri; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D010024:Osteoporosis / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D019936:Probiotics / Q000494:pharmacology / Q000627:therapeutic use*; D051153:Wnt Proteins / Q000378:metabolism*
chemical_list: D051153:Wnt Proteins; C102068:Wnt10b protein, mouse