title: Long-Term Administration of High-Fat Diet Corrects Abnormal Bone Remodeling in the Tibiae of Interleukin-6-Deficient Mice.
abstract: In this study, we aimed to evaluate the influence of diet-induced obesity on IL-6 deficiency-induced bone remodeling abnormality. Seven-week-old IL-6(-/-) mice and their wild type (WT) littermates were fed a standard diet (SD) or high-fat diet (HFD) for 25 weeks. Lipid formation and bone metabolism in mice tibiae were investigated by histochemical analysis. Both IL-6(-/-) and WT mice fed the HFD showed notable body weight gain, thickened cortical bones, and adipose accumulation in the bone marrow. Notably, the HFD normalized the bone phenotype of IL-6(-/-) mice to that of their WT counterpart, as characterized by a decrease in bone mass and the presence of an obliquely arranged, plate-like morphology in the trabecular bone. Alkaline phosphatase and osteocalcin expressions were attenuated in both genotypes after HFD feeding, especially for the IL-6(-/-) mice. Meanwhile, tartrate-resistant acid phosphatase staining was inhibited, osteoclast apoptosis rate down-regulated (revealed by TUNEL assay), and the proportion of cathepsin K (CK)-positive osteoclasts significantly increased in IL-6(-/-) mice on a HFD as compared with IL-6(-/-) mice on standard chow. Our results demonstrate that HFD-induced obesity reverses IL-6 deficiency-associated bone metabolic disorders by suppressing osteoblast activity, upregulating osteoclastic activity, and inhibiting osteoclast apoptosis.
authors.affiliation: Department of Bone Metabolism, School of Stomatology Shandong University, Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan, China (WF, BL, DL, WW, XH, JC, ML)
authors.forename: Wei
authors.initials: W
authors.lastname: Feng
authors.affiliation: Department of Bone Metabolism, School of Stomatology Shandong University, Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan, China (WF, BL, DL, WW, XH, JC, ML)
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Bone Metabolism, School of Stomatology Shandong University, Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan, China (WF, BL, DL, WW, XH, JC, ML)
authors.forename: Di
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Developmental Biology of Hard Tissue, Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan(TH, NA)
authors.forename: Tomoka
authors.initials: T
authors.lastname: Hasegawa
authors.affiliation: Department of Bone Metabolism, School of Stomatology Shandong University, Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan, China (WF, BL, DL, WW, XH, JC, ML)
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Bone Metabolism, School of Stomatology Shandong University, Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan, China (WF, BL, DL, WW, XH, JC, ML)
authors.forename: Xiuchun
authors.initials: X
authors.lastname: Han
authors.affiliation: Department of Bone Metabolism, School of Stomatology Shandong University, Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan, China (WF, BL, DL, WW, XH, JC, ML)
authors.forename: Jian
authors.initials: J
authors.lastname: Cui
authors.affiliation: Department of Advanced Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan (Y)
authors.lastname: Yimin
authors.affiliation: Division of Biochemistry, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan (KO)
authors.forename: Kimimitsu
authors.initials: K
authors.lastname: Oda
authors.affiliation: Department of Developmental Biology of Hard Tissue, Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan(TH, NA)
authors.forename: Norio
authors.initials: N
authors.lastname: Amizuka
authors.affiliation: Department of Bone Metabolism, School of Stomatology Shandong University, Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan, China (WF, BL, DL, WW, XH, JC, ML)
authors.forename: Minqi
authors.initials: M
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects*; D059305:Diet, High-Fat / Q000009:adverse effects*; D015850:Interleukin-6 / Q000172:deficiency*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000139:chemically induced / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013977:Tibia / Q000002:abnormalities* / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors
chemical_list: D015850:Interleukin-6; C577686:interleukin-6, mouse
keywords: IL-6; bone metabolism; obesity; osteoblast; osteoclast