Jin Xin, Zhu Liguo, Li Xiulan, Jia Jian, Zhang Yang, Sun Xiaolei, Ma Jianxiong, Liu Zhaojie, Ma Xinlong
Orthopedics Department, Tianjin Hospital, Tianjin 300050, P.R. China.
Orthopedics Department, China Academy of Traditional Chinese Medicine, Beijing 100102, P.R. China.
Mol Med Rep. 2017 Feb;15(2):890-898. doi: 10.3892/mmr.2016.6062. Epub 2016 Dec 20.
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.
岩藻依聚糖是一种从海藻中分离出的硫酸化多糖。本研究使用了经岩藻依聚糖处理的去卵巢Sprague-Dawley大鼠。采用显微计算机断层扫描（CT）、组织形态计量学分析、骨代谢生化标志物（血清I型前胶原N端前肽和C端端肽-1）以及股骨力学性能测试，评估岩藻依聚糖对骨代谢、密度和微结构的影响。此外，研究了低分子量岩藻依聚糖（LMWF）对体外培养破骨细胞的影响，以确定LMWF诱导破骨细胞抑制的潜在机制。在去卵巢大鼠中，LMWF增加了股骨骨密度。显微CT扫描还显示，LMWF可防止微结构恶化，组织形态计量学分析表明，LMWF增加了小梁骨数量并减少了骨吸收表面。此外，LMWF降低了去卵巢大鼠的高骨转换率，并改善了股骨的力学性能。体外实验表明，LMWF抑制核因子κB受体活化因子配体（RANKL）和巨噬细胞集落刺激因子诱导的RAW264.7细胞分化为抗酒石酸酸性磷酸酶（TRAP）阳性破骨细胞，并减少了破骨细胞的骨吸收表面。逆转录-定量聚合酶链反应表明，LMWF抑制了TRAP、基质金属肽酶-9、活化T细胞核激活因子1和破骨细胞相关免疫球蛋白样受体的mRNA表达，这些都是破骨细胞分化信号通路的组成部分。LMWF对RANK mRNA表达没有影响。总之，本研究证实LMWF抑制破骨细胞分化和骨吸收，可能是去卵巢大鼠骨质疏松症的一种潜在治疗方法。
