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通过氯化锂/磷酸钙水泥释放的锂离子激活 Wnt/β-连环蛋白信号通路加速骨质疏松症中的骨再生。

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

机构信息

Department of Orthopedics, Fourth Affiliated Hospital of Guangxi Medical University/Liu Zhou Worker's Hospital, Liuzhou, Guangxi 545005, China.

Center for Human Tissues and Organs Degeneration, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, China.

出版信息

Sci Rep. 2017 Mar 24;7:45204. doi: 10.1038/srep45204.

DOI:10.1038/srep45204
PMID:28338064
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5364554/
Abstract

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.

摘要

凭借其优异的生物活性和骨诱导性,磷酸钙水泥(CPC)已广泛应用于骨工程领域。在 CPC 中掺杂微量元素可以改变其物理特性并增强成骨作用。微量元素锂已被证明可以刺激成骨细胞的增殖和分化。我们研究了掺锂磷酸钙水泥(Li/CPC)治疗骨质疏松性骨缺损的愈合效果及其潜在机制。浸泡在模拟体液中的 Li/CPC 体逐渐转化为羟基磷灰石。Li/CPC 浸提液通过体外激活 Wnt/β-catenin 通路,在释放出 25.35±0.12 至 50.74±0.13mg/L 的锂离子(Li)时,刺激成骨细胞的增殖和分化。我们还研究了局部给予 Li 对 CPC 和 Li/CPC 体内大鼠胫骨缺损的影响。微计算机断层扫描和组织学染色显示,与 CPC 相比,Li/CPC 通过增加骨量和促进缺损修复,具有更好的成骨作用(P<0.05)。Li/CPC 还表现出更好的骨传导性和骨整合性。这些发现表明,Li/CPC 局部释放的 Li 通过激活 Wnt/β-catenin 通路可能加速骨质疏松性损伤的骨再生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d334/5364554/2812f4c96bb1/srep45204-f9.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d334/5364554/2812f4c96bb1/srep45204-f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d334/5364554/b153cf8211a2/srep45204-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d334/5364554/c0c7db06f824/srep45204-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d334/5364554/f2735d305f8b/srep45204-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d334/5364554/cc289bdbb48e/srep45204-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d334/5364554/2d3fa6109d02/srep45204-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d334/5364554/4a7be72e65dc/srep45204-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d334/5364554/7d36a2cd46c8/srep45204-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d334/5364554/9239a03355a7/srep45204-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d334/5364554/2812f4c96bb1/srep45204-f9.jpg

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