Acceleration of bone regeneration by activating Wnt/β-catenin signalling pathway via lithium released from lithium chloride/calcium phosphate cement in osteoporosis.

Acceleration of bone regeneration by activating Wnt/β-catenin signalling pathway via lithium released from lithium chloride/calcium phosphate cement in osteoporosis.
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DOI:
10.1038/srep45204
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发表时间:
2017-03-24
期刊:
影响因子:
4.6
通讯作者:
Li B
Li B
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Li L;Peng X;Qin Y;Wang R;Tang J;Cui X;Wang T;Liu W;Pan H;Li B

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磷酸钙骨水泥(CPC)凭借其良好的生物活性和骨传导性,在骨工程中得到了广泛的应用。在CPC中掺入微量元素可以改变其物理特性,促进成骨。微量元素锂具有促进成骨细胞增殖和分化的作用。探讨锂掺杂磷酸钙骨水泥(Li/CPC)对骨质疏松性骨缺损的修复作用及其机制。浸泡在模拟体液中的Li/CPC骨料逐渐转化为羟基磷灰石。当锂离子(Li+)在25.35 ± 0.12~50.74 ± 0.13 mg/L释放时,Li/CPC提取物通过激活Wnt/β-连环蛋白途径,在体外刺激成骨细胞的增殖和分化。我们还观察了局部应用Li+对大鼠胫骨中CPC和Li/CPC之间的损伤的影响。显微计算机断层扫描和组织学染色显示,Li/Cpc具有更好的成骨作用,增加了骨量,促进了缺损区的修复(P < 005)。Li/CPC具有更好的骨传导性和骨整合能力。这些结果提示,在骨质疏松中,Li/CPC局部释放的Li+可能通过激活Wnt/β-连环蛋白途径来促进损伤后的骨再生。
By virtue of its excellent bioactivity and osteoconductivity, calcium phosphate cement (CPC) has been applied extensively in bone engineering. Doping a trace element into CPC can change physical characteristics and enhance osteogenesis. The trace element lithium has been demonstrated to stimulate the proliferation and differentiation of osteoblasts. We investigated the fracture-healing effect of osteoporotic defects with lithium-doped calcium phosphate cement (Li/CPC) and the underlying mechanism. Li/CPC bodies immersed in simulated body fluid converted gradually to hydroxyapatite. Li/CPC extracts stimulated the proliferation and differentiation of osteoblasts upon release of lithium ions (Li+) at 25.35 ± 0.12 to 50.74 ± 0.13 mg/l through activation of the Wnt/β-catenin pathway in vitro. We also examined the effect of locally administered Li+ on defects in rat tibia between CPC and Li/CPC in vivo. Micro-computed tomography and histological staining showed that Li/CPC had better osteogenesis by increasing bone mass and promoting repair in defects compared with CPC (P < 0.05). Li/CPC also showed better osteoconductivity and osseointegration. These findings suggest that local release of Li+ from Li/CPC may accelerate bone regeneration from injury through activation of the Wnt/β-catenin pathway in osteoporosis.