Department of Orthopaedics, St Vincent's Health, University of Melbourne, Fitzroy 3065, Australia.
Department of Orthopaedics, the First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China.
Biomaterials. 2014 Sep;35(27):7828-38. doi: 10.1016/j.biomaterials.2014.05.087. Epub 2014 Jun 17.
Bone defects caused by fractures or cancer-mediated destruction are debilitating. Chitosan is commonly used in scaffold matrices for bone healing, but rarely as a free drug. We demonstrate that free chitosan promotes osteoblast proliferation and osteogenesis in mesenchymal stem cells, increases osteopontin and collagen I expression, and reduces osteoclastogenesis. Chitosan inhibits invasion of endothelial cells, downregulating uPA/R, MT1-MMP, cdc42 and Rac1. Better healing of bone fractures with greater trabecular bone formation was observed in mice treated with chitosan. Chitosan induces apoptosis in osteotropic prostate and breast cancer cells via caspase-2 and -3 activation, and reduces their establishment in bone. Chitosan is pro-apoptotic in osteosarcoma cells, but not their normal counterpart, osteoblasts, or chondrosarcoma cells. Systemic delivery of chitosan does not perturb angiogenesis, bone volume or instinctive behaviour in pregnant mice, but decreases foetal length and changes pancreatic secretory acini. With certain controls in place, chitosan could be useful for bone trauma management.
由骨折或癌症介导的破坏引起的骨缺损是使人衰弱的。壳聚糖常用于骨愈合的支架基质，但很少作为游离药物使用。我们证明游离壳聚糖可促进间充质干细胞中成骨细胞的增殖和骨生成，增加骨桥蛋白和胶原 I 的表达，并减少破骨细胞的生成。壳聚糖抑制内皮细胞的侵袭，下调 uPA/R、MT1-MMP、cdc42 和 Rac1。用壳聚糖处理的小鼠观察到骨折愈合更好，小梁骨形成更多。壳聚糖通过半胱天冬酶-2 和 -3 的激活诱导亲骨性前列腺癌和乳腺癌细胞凋亡，并减少其在骨中的定植。壳聚糖对骨肉瘤细胞具有促凋亡作用，但对其正常对应物成骨细胞或软骨肉瘤细胞没有作用。壳聚糖在怀孕小鼠中全身给药不会干扰血管生成、骨量或本能行为，但会降低胎儿长度并改变胰腺分泌的腺泡。在采取某些控制措施的情况下，壳聚糖可用于管理骨创伤。
