The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Wuhan 430079, PR China.
Biomaterials. 2012 Oct;33(28):6698-708. doi: 10.1016/j.biomaterials.2012.06.021. Epub 2012 Jul 2.
Osteoporosis is a chronic disease affecting millions of people worldwide caused by an imbalance between bone-forming osteoblasts and bone-resorbing osteoclasts. Despite recent developments in pharmacological agents to prevent osteoporotic-related fractures, much less attention has been placed on the repair of bone defects following fracture. Critical to this process is the recruitment of mesenchymal stem cells (MSCs) to defect sites by growth factors. One method which has been effective for the sustained release of growth factors is that of gene therapy. The aim of the present study was to investigate newly developed mesoporous bioglass/silk fibrin scaffolds containing adPDGF-b and adBMP-7 into osteoporotic critical-sized femur defects in ovariectomised rats following treatment periods of 2 and 4 weeks. In vivo osteogenetic efficiency evaluated by μ-CT analysis, hematoxylin and eosin staining, and immunohistochemical (type I collagen, osteopontin and BSP) revealed significantly new bone formation in defects containing adenovirus for both PDGF-b and BMP-7 when compared to scaffolds alone and scaffolds containing BMP-7. TRAP-positive staining also demonstrated the ability for these scaffolds to be degraded over time and initiate bone turnover/remodeling. Although the use of gene therapy for clinical applications is still in its infancy, results from the present study demonstrate their potent ability to recruit mesenchymal progenitor cells through sustained release of PDGF-b and BMP-7 which may be beneficial for patients suffering from osteoporotic-related fractures.
骨质疏松症是一种全球性的慢性疾病,影响着数以百万计的人,其病因是成骨细胞和成骨细胞之间的失衡。尽管最近在预防骨质疏松性骨折的药物方面取得了进展,但对于骨折后骨缺损的修复关注较少。这个过程的关键是生长因子募集间充质干细胞(MSCs)到缺损部位。一种有效的生长因子持续释放方法是基因治疗。本研究的目的是研究新开发的介孔生物玻璃/丝素纤维支架,该支架中含有 adPDGF-b 和 adBMP-7,用于治疗去卵巢大鼠骨质疏松性临界股骨缺损 2 周和 4 周后的大鼠。通过 μ-CT 分析、苏木精和伊红染色以及免疫组织化学(I 型胶原、骨桥蛋白和 BSP)评估体内成骨效率,结果显示,与单独支架和仅含 BMP-7 的支架相比,含有 adPDGF-b 和 BMP-7 的腺病毒的支架在缺陷部位具有明显的新骨形成。TRAP 阳性染色也表明这些支架能够随着时间的推移降解并启动骨转换/重塑。尽管基因治疗在临床应用中仍处于起步阶段,但本研究的结果表明,它们通过持续释放 PDGF-b 和 BMP-7 募集间充质祖细胞的能力很强,这可能对患有骨质疏松性骨折的患者有益。