INSERM U957, Faculté de Médecine, Université de Nantes, Nantes, France.
Glycobiology. 2011 Jun;21(6):781-95. doi: 10.1093/glycob/cwr002. Epub 2011 Mar 8.
The growth and differentiation of bone cells is controlled by various factors, which can be modulated by heparan sulfates. Here, we investigated the effects of an oversulfated exopolysaccharide (OS-EPS) on the bone. We compared the effect of this compound with that of a native EPS. Long-term administration of OS-EPS causes cancellous bone loss in mice due, in part, to an increase in the number of osteoclasts lining the trabecular bone surface. No significant difference in cancellous bone volume was found between EPS-treated mice and age-matched control mice, underlying the importance of sulfation in trabecular bone loss. However, the mechanism sustaining this osteoporosis was unclear. To clarify OS-EPS activities, we investigated the effect of OS-EPS on osteogenesis. Our results demonstrated that OS-EPS inhibited osteoclastogenesis in two cell models. Using the surface plasmon resonance technique, we revealed that OS-EPS can form a hetero-molecular complex OS-EPS/receptor activator of NF-κB ligand (RANKL)/RANK and that RANK had a higher affinity for RANKL pre-incubated with OS-EPS than for RANKL alone, which would be in favor of an increase in bone resorption. However, in vitro, OS-EPS inhibited the early steps of osteoclast precursor adhesion and therefore inhibited the cell fusion step. In addition, we showed that OS-EPS reduced proliferation and accelerated osteoblastic differentiation, leading to strong inhibition of mineralized nodule formation, which would be in favor of an increase in bone resorption. Taken together, these data show different levels of bone resorption regulation by EPSs, most of them leading to proresorptive effects.
细胞的生长和分化受多种因素控制，这些因素可以被硫酸乙酰肝素调节。在这里，我们研究了一种过硫酸化胞外多糖（OS-EPS）对骨骼的影响。我们比较了这种化合物和天然 EPS 的作用。OS-EPS 的长期给药会导致小鼠松质骨丢失，部分原因是骨小梁表面破骨细胞数量的增加。与 EPS 处理的小鼠相比，年龄匹配的对照小鼠的松质骨体积没有显著差异，这表明硫酸化在小梁骨丢失中很重要。然而，维持这种骨质疏松症的机制尚不清楚。为了阐明 OS-EPS 的作用机制，我们研究了 OS-EPS 对成骨的影响。我们的结果表明，OS-EPS 在两种细胞模型中抑制破骨细胞生成。通过表面等离子体共振技术，我们揭示 OS-EPS 可以形成 OS-EPS/核因子-κB 受体激活剂配体（RANKL）/RANK 异源分子复合物，并且 OS-EPS 预孵育的 RANKL 与单独的 RANKL 相比，RANK 对 RANKL 的亲和力更高，这有利于骨吸收的增加。然而，在体外，OS-EPS 抑制破骨细胞前体细胞的早期黏附步骤，从而抑制细胞融合步骤。此外，我们表明 OS-EPS 抑制增殖并加速成骨细胞分化，导致矿化结节形成强烈抑制，这有利于骨吸收的增加。综上所述，这些数据表明 EPS 以不同的水平调节骨吸收，其中大多数导致促吸收作用。
