Abstract
Osteoporosis is associated with reduced density and quality of bone leading to weakened skeleton thereby increasing the risk of fractures responsible for increased morbidity and mortality. Due to preference for western food style the consumption of salt intake in our diets has increased many folds. High dietary salt intake has recently been linked with induction of Th17 cells along with impairment of Treg cells. Also, Th17 cells have been one of major players in the pathophysiology of various bone pathologies including osteoporosis. We thus hypothesized that high salt diet (HSD) intake would lead to enhanced bone loss by modulating Th17-Treg cell balance. In the present study, we report for the first time that HSD intake in male mice impairs both trabecular and cortical bone microarchitecture along with decreasing the mineral density and heterogeneity of bones. The HSD modulates host immune system and skews Treg-Th17 balance by promoting osteoclastogenic Th17 cells and inhibiting development of anti-osteoclastogenic Treg cells in mice. HSD also enhanced expression of proinflammatory cytokines (IL-6, TNF-α, RANKL and IL-17) and decreased the expression of anti-inflammatory cytokines (IL-10, IFN-γ). Taken together the present study for the first time establishes a strong correlation between high dietary salt intake and bone health via interplay between Th17-Treg cells.
Highlights
Osteoporosis is an increasingly common chronic condition of bones with more than 200 million affected individuals worldwide[1]
To determine the effect of high dietary salt intake on bone health we were first interested in looking for different signs of bone remodelling by scanning the surface of bones by scanning electron microscopy (SEM) and atomic force microscopy (AFM)
To determine the same we divided the mice in three group’s viz. normal (0.8% in chow + normal drinking water), low salt diet (LSD) (0.4% in chow + normal drinking water) and high salt diet (HSD) intake (4% in chow + 1% drinking water) groups (Fig. 1A) and at day 45 (Supplementary Fig. S1, S2 and S3) mice were sacrificed and femur bones collected for SEM and AFM
Summary
Osteoporosis is an increasingly common chronic condition of bones with more than 200 million affected individuals worldwide[1]. As the salt war rages on, it has been linked to negative effect on bone health, as various recent studies have reported relationship between high salt intake and risk of osteoporosis[7,18]. Tregs can lead to suppression of bone loss by inhibiting differentiation of monocytes into osteoclasts under both in vitro and in vivo conditions[23,24] It has been reported by Jörg et al that HSD induces the generation of pathogenic Th17 cells in experimental autoimmune encephalomyelitis (EAE)[25]. We report for the first time that high dietary salt intake impairs bone-microarchitecture and induces bone loss by modulating Treg-Th17 cell balance. The present study demonstrates the unique role of diet, high salt in bone health; and opens up Pandora’s Box for future research in the novel field of “Nutritional Therapeutics”
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