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

Abstract

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.

Efficacy of marine bioactive compound fucoidan for bone regeneration and implant fixation in sheep

“…Our results are further supported by Jin et al 40 and Lu et al 17 LMW FUC prevented bone turnover in ovariectomized rats, as micro‐CT showed a higher BV/TV and TbTh in rats treated with FUC than without FUC 40 . Histomorphometric analysis further demonstrated this, with a reduced bone turnover rate was found in the FUC group compared to ovariectomized rats without FUC 40 . Lu et al also demonstrated reduced bone turnover: micro‐CT and bone histomorphometry found that FUC treatment markedly prevented lipopolysaccharide‐induced bone erosion in mice 17 .…”

Effect of Enzymatically Extracted Fucoidans on Angiogenesis and Osteogenesis in Primary Cell Culture Systems Mimicking Bone Tissue Environment

“…According to literature, fucoidan can affect bone health by influencing osteoblast differentiation as well as bone resorption [ 36 , 37 ], both processes that depend on VEGF as a central regulatory molecule. In contrast to our observation, a number of studies show that fucoidans promote osteoblast differentiation [ 38 , 39 , 40 ].…”

Biological Activities of Fucoidan and the Factors Mediating Its Therapeutic Effects: A Review of Recent Studies

“…Regarding its osteogenic effects, 3D culture systems are predicted to narrow the gap between in vitro studies and clinical trials [150]. Of the in vivo experiments performed, LMWF has been shown to inhibit osteoclast differentiation and bone resorption in ovariectomized Sprague-Dawley rats, demonstrating its potential in the treatment of osteoporosis [151]. The extraction of LMWF from fresh Sargassum hemiphyllum also increased bone density and ash weight in C57BL/6J female mice [152].…”