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- Lawenius, Lina, et al.
(författare)
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Development of a synbiotic that protects against ovariectomy-induced trabecular bone loss
- 2022
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Ingår i: American Journal of Physiology-Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 322:4
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Tidskriftsartikel (refereegranskat)abstract
- The gut microbiome has the capacity to regulate bone mass. The aim of this study was to develop a nutritional synbiotic dietary assemblage at an optimal dose to maintain bone mass in ovariectomized (Ovx) mice. We performed genomic analyses and in vitro experiments in a large collection of bacterial and fungal strains (>4,000) derived from fresh fruit and vegetables to identify candidates with the synergistic capacity to produce bone-protective short-chain fatty acids (SCFA) and vitamin K2. The candidate SBD111-A, composed of Lactiplantibacillus plantarum, Levilactobacillus brevis, Leuconostoc mesenteroides, Pseudomonas fluorescens, and Pichia kudriavzevii together with prebiotic dietary fibers, produced high levels of SCFA in vitro and protected against Ovx-induced trabecular bone loss in a dose-dependent manner in mice. Metagenomic sequencing revealed that SBD111-A changed the taxonomic composition and enriched specific pathways for synthesis of bone-protective SCFA, vitamin K2, and branched-chain amino acids in the gut microbiome. NEW & NOTEWORTHY We performed genomic analyses and in vitro experiments in a collection of bacterial and fungal strains. We identified a combination (SBD111-A) that produced high levels of SCFA in vitro and protected against ovariectomy-induced bone loss in a dose-dependent manner in mice. Metagenomic sequencing revealed that SBD111-A changed the taxonomic composition and function of the gut microbiome and enriched pathways for synthesis of bone-protective SCFA, vitamin K2, and branched-chain amino acids.
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| 2. |
- Lawenius, Lina, et al.
(författare)
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Pasteurized Akkermansia muciniphila protects from fat mass gain but not from bone loss
- 2020
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Ingår i: American Journal of Physiology-Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 318:4
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Tidskriftsartikel (refereegranskat)abstract
- Probiotic bacteria can protect from ovariectomy (ovx)-induced bone loss in mice. Akkermansia muciniphila is considered to have probiotic potential due to its beneficial effect on obesity and insulin resistance. The purpose of the present study was to determine if treatment with pasteurized Akkermansia muciniphila (pAkk) could prevent ovx-induced bone loss. Mice were treated with vehicle or pAkk for 4 wk, starting 3 days before ovx or sham surgery. Treatment with pAkk reduced fat mass accumulation confirming earlier findings. However, treatment with pAkk decreased trabecular and cortical bone mass in femur and vertebra of gonadal intact mice and did not protect from ovx-induced bone loss. Treatment with pAkk increased serum parathyroid hormone (PTH) levels and increased expression of the calcium transporter Trpv5 in kidney suggesting increased reabsorption of calcium in the kidneys. Serum amyloid A 3 (SAA3) can suppress bone formation and mediate the effects of PTH on bone resorption and bone loss in mice and treatment with pAkk increased serum levels of SAA3 and gene expression of Saa3 in colon. Moreover, regulatory T cells can be protective of bone and pAkk-treated mice had decreased number of regulatory T cells in mesenteric lymph nodes and bone marrow. In conclusion, treatment with pAkk protected from ovx-induced fat mass gain but not from bone loss and reduced bone mass in gonadal intact mice. Our findings with pAkk differ from some probiotics that have been shown to protect bone mass, demonstrating that not all prebiotic and probiotic factors have the same effect on bone.
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| 6. |
- Lagerquist, Marie K, et al.
(författare)
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Reduction of Mature B Cells and Immunoglobulins Results in Increased Trabecular Bone
- 2022
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Ingår i: Jbmr Plus. - : Wiley. - 2473-4039. ; 6:9
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Tidskriftsartikel (refereegranskat)abstract
- Inflammation has a significant effect on bone remodeling and can result in bone loss via increased stimulation of osteoclasts. Activated immunoglobulins, especially autoantibodies, can increase osteoclastogenesis and are associated with pathological bone loss. Whether immunoglobulins and mature B lymphocytes are important for general bone architecture has not been completely determined. Here we demonstrate, using a transgenic mouse model, that reduction of mature B cells and immunoglobulins leads to increased trabecular bone mass compared to wild-type (WT) littermate controls. This bone effect is associated with a decrease in the number of osteoclasts and reduced bone resorption, despite decreased expression of osteoprotegerin. We also demonstrate that the reduction of mature B cells and immunoglobulins do not prevent bone loss caused by estrogen deficiency or arthritis compared to WT littermate controls. In conclusion, the reduction of mature B cells and immunoglobulins results in disturbed regulation of trabecular bone turnover in healthy conditions but is dispensable for pathological bone loss. (c) 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
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| 7. |
- Scheffler, Julia M., et al.
(författare)
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Interleukin 17A: a Janus-faced regulator of osteoporosis
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Interleukin (IL)-17A is a well-described mediator of bone resorption in inflammatory diseases, and postmenopausal osteoporosis is associated with increased serum levels of IL-17A. Ovariectomy (OVX) can be used as a model to study bone loss induced by estrogen deficiency and the role of IL-17A in osteoporosis development has previously been investigated using various methods to inhibit IL-17A signaling in this model. However, the studies show opposing results. While some publications reported IL-17A as a mediator of OVX-induced osteoporosis, others found a bone-protective role for IL-17 receptor signaling. In this study, we provide an explanation for the discrepancies in previous literature and show for the first time that loss of IL-17A has differential effects on OVX-induced osteoporosis; with IL-17A being important for cortical but not trabecular bone loss. Interestingly, the decrease in trabecular bone after OVX in IL-17A knock-out mice, was accompanied by increased adipogenesis depicted by elevated leptin levels. Additionally, the bone marrow adipose tissue expanded, and the bone-turnover decreased in ovariectomized mice lacking IL-17A compared to ovariectomized WT mice. Our results increase the understanding of how IL-17A signaling influences bone remodeling in the different bone compartments, which isof importance for the development of new treatments of post-menopausal osteoporosis. © 2020, The Author(s).
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