Synergistic effects of phytochemical cocktail and aerobic exercise on mRNA and lncRNA networks modulating bone turnover in hypothyroid mice.

Introduction: Metabolic bone disease (MBD) is a multifactorial condition that leads to microarchitectural and bone mass disturbance. The association and mechanisms between MBD and hypothyroidism are not comprehensively elucidated. Moreover, long non-coding RNAs (lncRNAs), as critical regulators in biological processes, are one category of RNAs that could regulate gene expression through various mechanisms.

Methods: Artificial intelligence indicated several mRNAs-lncRNAs involved in the bone tissue in hypothyroidism conditions. After in-silico and chemoinformatic analysis, 30 female C57BL/6 mice at six weeks old and an approximate weight of 24±2 g were divided into five subgroups (n=6 mice/groups), including 1) hypothyroidism in mice (HYPO), 2) hypothyroidism in mice treated with Dorema aucheri (DA) extract (0.4 mg/kg), 3) hypothyroidism in mice treated with aerobic exercise (AE), 4) hypothyroidism in mice treated DA extract bioactive compound along with AE, 5) Normal group (without any induction and treatments). Real-Time PCR detected the relative expression of mRNA and lncRNAs.

Results: We indicated that the osteoblast and osteoclast markers are dysregulated in hypothyroidism. In addition, DA and AE modified the bone remodeling, bone resorption markers, and inhibitors of Wnt/beta-catenin. We revealed that Adipoq, Dnmt1, Sirt-1, Ppar-ɑ, Ncor1, and Ctnnb1 networks are dysregulated in hypothyroidism conditions. DA and AE modulated this network in bone tissue. The relative expression of the four lncRNAs (TUG1, HOTAIR, H19, and MEG3) was altered in hypothyroidism. Notably, DA and AE significantly regulated the expression level of these lncRNAs.

Conclusion: AE and DA complementary and alternative medicine ameliorated the metabolic bone disease induced by hypothyroidism in mice.