Low-molecular weight fucoidan inhibits the differentiation of osteoclasts and reduces osteoporosis in ovariectomized rats

Abstract

Fucoidan is a type of sulfated polysaccharide isolated from seaweed. The present study used ovariectomized Sprague-Dawley rats, which were treated with fucoidan. The effects of fucoidan on bone metabolism, density and microarchitecture were assessed using micro-computed tomography (CT), histomorphometric analysis, biochemical markers of bone metabolism (Serum procollagen type I N propeptide and C-terminal telopeptide-1) and tests of mechanical competence of the femur. In addition, the effects of low-molecular weight fucoidan (LMWF) on in vitro cultured osteoclasts were examined, in order to determine the mechanisms underlying LMWF-induced osteoclastic inhibition. In ovariectomized rats, LMWF increased femoral bone density. Micro-CT 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 colony-stimulating factor-induced differentiation of RAW264.7 cells into tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts, and reduced the bone resorption surface of the osteoclasts. Reverse transcription-quantitative polymerase chain reaction demonstrated that LMWF inhibited mRNA expression of TRAP, matrix metallopeptidase-9, nuclear activator of activated T-cells 1, and osteoclast-associated immunoglobulin-like 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.