Lowmolecular weight fucoidan inhibits the differentiation of osteoclasts and reduces osteoporosis in ovariectomized rats

Fucoidan is a type of sulfated polysaccharide isolated from seaweed. The present study used ovariectomized SpragueDawley rats, which were treated with fucoidan. The effects of fucoidan on bone metabolism, density and microarchitecture were assessed using microcomputed tomography (CT), histomorphometric analysis, biochemical markers of bone metabolism (Serum procollagen type I N propeptide and Cterminal telopeptide1) and tests of mechanical competence of the femur. In addition, the effects of lowmolecular weight fucoidan (LMWF) on in vitro cultured osteoclasts were examined, in order to determine the mechanisms underlying LMWFinduced osteoclastic inhibition. In ovariectomized rats, LMWF increased femoral bone density. MicroCT scan also revealed that LMWF prevented microarchitectural deterioration and histomorphometric analysis determined that LMWF increased trabecular bone number and reduced the surface of bone resorption. In addition, LMWF reduced the high bone turnover rate, and improved the mechanical properties of the femur in ovariectomized rats. In vitro experiments revealed that LMWF inhibited the receptor activator of nuclear factor κB ligand (RANKL) and macrophage colonystimulating factorinduced differentiation of RAW264.7 cells into tartrateresistant acid phosphatase (TRAP)positive osteoclasts, and reduced the bone resorption surface of the osteoclasts. Reverse transcriptionquantitative polymerase chain reaction demonstrated that LMWF inhibited mRNA expression of TRAP, matrix metallopeptidase9, nuclear activator of activated Tcells 1, and osteoclastassociated immunoglobulinlike receptor, which are components of the signaling pathway for osteoclast differentiation. LMWF had no effect on RANK mRNA expression. In conclusion, the present study confirmed that LMWF inhibited osteoclast differentiation and bone resorption, and may be a potential treatment for osteoporosis in ovariectomized rats.