Microcystin-leucine arginine (MC-LR) induces bone loss and impairs bone micro-architecture by modulating host immunity in mice: Implications for bone health

Highlights: • Inflammatory bone loss is one of the most commonly occurring bone conditions in the world. • MC-LR is one of the most abundantly found cyanobacterial toxin around the world, effecting both human and animal health. • The study for the first time demonstrates the direct effect of MC-LR on bone health (osteo-toxicology) via affecting the host osteo-immune system. • The study thus highlights the risk associated with intake of MC-LR contaminated water and food to our osteo-immune system with immense future implications in the field. Osteoporosis or enhanced bone loss is one of the most commonly occurring bone conditions in the world, responsible for higher incidence of fractures leading to increased morbidity and mortality in adults. Bone loss is affected by various environmental factors including diet, age, drugs, toxins etc. Microcystins are toxins produced by cyanobacteria with microcystin-LR being the most abundantly found around the world effecting both human and animal health. The present study demonstrates that MC-LR treatment induces bone loss and impairs both trabecular and cortical bone microarchitecture along with decreasing the mineral density and heterogeneity of bones in mice. This effect of MC-LR was found due to its immunomodulatory effects on the host immune system, wherein MC-LR skews both T cell (CD4⁺ and CD8⁺ T cells) and B cell populations in various lymphoid tissues. MC-LR further was found to significantly enhance the levels of osteoclastogenic cytokines (IL-6, IL-17 and TNF-α) along with simultaneously decreasing the levels of anti-osteoclastogenic cytokines (IL-10 and IFN-γ). Taken together, our study for the first time establishes a direct link between MC-LR intake and enhanced bone loss thereby giving a strong impetus to the naïve field of "osteo-toxicology", to delineate the effects of various toxins (including cyanotoxins) on bone health.