Sulfated Glucuronorhamnoxylan from Capsosiphon fulvescens Ameliorates Osteoporotic Bone Resorption via Inhibition of Osteoclastic Cell Differentiation and Function In Vitro and In Vivo

Excessive osteoclast differentiation and/or bone resorptive function causes a gradual loss of bone, leading to the pathogenesis of bone diseases such as osteoporosis (OP). In this study, a sulfated glucuronorhamnoxylan polysaccharide (designated SPS-CF) of the green alga Capsosiphon fulvescens was evaluated for anti-osteoporotic activity using osteoclastic cells differentiated from RAW264.7 macrophages by receptor activator of NF-kappa B ligand (RANKL) treatment and ovariectomized (OVX) female mice as a postmenopausal OP model. With negligible cytotoxicity, SPS-CF (50 mu g/mL) significantly suppressed tartrate-resistant acid phosphatase (TRAP) activity, actin ring formation, and expression of matrix metalloproteinase 9 (MMP-9), cathepsin K, TRAF6, p-Pyk2, c-Cbl, c-Src, gelsolin, carbonic anhydrase II (CA II), and integrin beta 3, indicating that SPS-CF inhibits the differentiation and bone resorptive function of osteoclasts. Removal of sulfate groups from SPS-CF abolished its anti-osteoclastogenic activities, demonstrating that sulfate groups are critical for its activity. Oral administration of SPS-CF (400 mg/kg/day) to OVX mice significantly augmented the bone mineral density (BMD) and serum osteoprotegerin (OPG)/RANKL ratio. These results demonstrated that SPS-CF exerts significant anti-osteoporotic activity by dampening osteoclastogenesis and bone resorption via downregulation of TRAF6-c-Src-Pyk2-c-Cbl-gelsolin signaling and augmentation of serum OPG/RANKL ratios in OVX mice, suggesting that SPS-CF can be a novel anti-osteoporotic compound for treating postmenopausal OP.

Automated summary

In this study, the anti-osteoporotic activity of a sulfated glucuronorhamnoxylan polysaccharide from Capsosiphon fulvescens was evaluated using osteoclastic cells and ovariectomized mice. The polysaccharide significantly inhibited the differentiation and function of osteoclasts, as well as promoted bone mineral density and serum osteoprotegerin/RANKL ratio in the mice. These findings suggest that the polysaccharide has potential as a novel anti-osteoporotic compound.