Short-chain fatty acids and FFAR2 as suppressors of bone resorption.

Short-chain fatty acids (SCFAs) exert a variety of immune and metabolic functions by binding to G-protein-coupled receptors, mainly free fatty acid receptor 2 (FFAR2). However, the effects of SCFAs and FFARs on bone remodeling, especially in alveolar bone, have been less explored. In this study, we investigated the influence of the SCFA/FFAR2 axis on alveolar bone. Bone samples from wild-type (WT) and FFAR2-deficient mice (FFAR2-/-) were analyzed using micro-CT, histology and qPCR. WT and FFAR2-/- animals received a high-fiber diet (HFD) reported to increase circulating levels of SCFAs. Additionally, we analyzed the effects of SCFAs and a synthetic FFAR2 agonist, phenylacetamide-1 (CTMB), on bone cell differentiation. The participation of histone deacetylase inhibitors (iHDACs) in the effects of SCFAs was further assessed in vitro. CTMB treatment was also evaluated in vivo during orthodontic tooth movement (OTM). FFAR2-/- mice exhibited deterioration of maxillary bone parameters. Consistent with this, FFAR2-/- mice exhibited a significant increase of OTM and changes in bone cell numbers and in the expression of remodeling markers. The HFD partially reversed bone loss in the maxillae of FFAR2-/- mice. In WT mice, the HFD induced changes in the bone markers apparently favoring a bone formation scenario. In vitro, bone marrow cells from FFAR2-/- mice exhibited increased differentiation into osteoclasts, while no changes in osteoblasts were observed. In line with this, differentiation of osteoclasts was diminished by SCFAs and CTMB. Moreover, CTMB treatment significantly reduced OTM. Pretreatment of osteoclasts with iHDACs did not modify the effects of SCFAs on these cells. In conclusion, SCFAs function as regulators of bone resorption. The effects of SCFAs on osteoclasts are dependent on FFAR2 activation and are independent of the inhibition of HDACs. FFAR2 agonists may be useful to control bone osteolysis.

High-refined carbohydrate diet promotes detrimental effects on alveolar bone and femur microarchitecture.

The impact of high-refined carbohydrate (HC) diet on fat accumulation, adipokines secretion and systemic inflammation is well described. However, it remains unclear whether these processes affect bone remodeling. OBJECTIVE: To investigate the effects of HC diet in the alveolar bone and femur parameters. METHODS: BalbC mice were fed with conventional chow or HC diet for 12 weeks. After experimental time maxillae, femur, blood and white adipose tissue samples were collected. RESULTS: The animals feed with HC diet exhibited considerable increase of adiposity index and adipose tissue levels of TNF-α, IL-6, IL-10, IL-1ß, TGF-ß and leptin. Microtomography analysis of maxillary bone revealed horizontal alveolar bone loss and disruption of trabecular bone in mice feed with HC diet. These deleterious effects were correlated with a disturbance in bone cells and an augmented expression of Rankl/Opg ratio. Consistently, similar effects were observed in femurs, which also exhibited a reduction in bone maximum load and stiffness. CONCLUSION: Our data indicates that HC diet consumption disrupts bone remodeling process, favoring bone loss. Underlying mechanisms relies on fat tissue accumulation and also in systemic and local inflammation.