Low-molecular-weight fucoidan ameliorates calcium-deficient-diet-induced bone loss and osteoarthritis via CaSR level regulation

Fucoidans-sulfated and fucosylated polysaccharides extracted from brown seaweed-reportedly accelerate bone growth and prevent osteoarthritis (OA) progression. In this study, we examined the effects of lowmolecular-weight fucoidan (LMF) on the molecular mechanism of extracellular calcium concentration in vitro and in vivo. In MG63 cells, LMF significantly increased the activity of alkaline phosphatase (ALP) and expression of calcium-sensing receptor (CaSR), runt-related transcription factor 2 (Runx2), and osteoprotegerin (OPG) under low- and normal-[Ca+2]0 conditions, but only decreased the expression of receptor activator of the nuclear factor kappa B ligand (RANKL) under normal-[Ca+2]0 conditions. In the calcium-deficient diet model, LMF significantly increased body length, growth rate, bone-specific ALP secretion, trabecular number, and CaSR protein expression, without body weight changes. In the OA model, LMF significantly increased bone volume and CaSR protein expression and reduced joint inflammation. Overall, our results indicate that LMF reduced calcium-deficientdiet-induced bone loss and OA via CaSR level regulation.