Department of Trauma, Hand and Reconstructive Surgery, University Hospital Münster, Germany.
BMC Musculoskelet Disord. 2011 Nov 21;12:263. doi: 10.1186/1471-2474-12-263.
Enhancing osteogenic capabilities of bone matrix for the treatment of fractures and segmental defects using growth factors is an active area of research. Recently, synthetic peptides like AC- 100, TP508 or p-15 corresponding to biologically active sequences of matrix proteins have been proven to stimulate bone formation. The platelet-derived growth factor (PDGF) BB has been identified as an important paracrine factor in early bone healing. We hypothesized that the combined use of PDGF-BB with synthetic peptides could result in an increase in proliferation and calcification of osteoblast-like cells.
Osteoblast-like cell cultures were treated with PDGF and synthetic peptides, singly and as combinations, and compared to non-treated control cell cultures. The cultures were evaluated at days 2, 5, and 10 in terms of cell proliferation, calcification and gene expression of alkaline phosphate, collagen I and osteocalcin.
Experimental findings revealed that the addition of PDGF, p-15 and TP508 and combinations of PDGF/AC-100, PDGF/p-15 and PDGF/TP508 resulted in an increase in proliferating osteoblasts, especially in the first 5 days of cultivation. Proliferation did not significantly differ between single factors and factor combinations (p > 0.05). The onset of calcification in osteoblasts occurred earlier and was more distinct compared to the corresponding control or PDGF stimulation alone. Significant difference was found for the combined use of PDGF/p-15 and PDGF/AC-100 (p < 0.05).
Our findings indicate that PDGF exhibits cooperative effects with synthetic peptides in differentiation and proliferation. These cooperative effects cause a significant early calcification of osteoblast-like cells (p < 0.05). We suggest the combination of synthetic peptides and PDGF as a potential clinical approach for accelerating bone healing or coating osteosynthesis materials.
使用生长因子增强骨基质的成骨能力以治疗骨折和节段性缺损是一个活跃的研究领域。最近,诸如 AC-100、TP508 或 p-15 等与基质蛋白的生物活性序列相对应的合成肽已被证明可刺激骨形成。血小板衍生生长因子(PDGF-BB)已被确定为早期骨愈合中的重要旁分泌因子。我们假设 PDGF-BB 与合成肽的联合使用可能导致成骨样细胞的增殖和钙化增加。
成骨样细胞培养物分别用 PDGF 和合成肽处理,单独和组合处理,并与未经处理的对照细胞培养物进行比较。在第 2、5 和 10 天,根据细胞增殖、钙化和碱性磷酸酶、胶原 I 和骨钙素的基因表达评估培养物。
实验结果表明,添加 PDGF、p-15 和 TP508 以及 PDGF/AC-100、PDGF/p-15 和 PDGF/TP508 的组合导致增殖的成骨细胞增加,特别是在培养的前 5 天。与单一因素相比,单一因素和因素组合之间的增殖没有显著差异(p>0.05)。与单独的 PDGF 刺激相比,成骨细胞中的钙化开始更早且更明显。在 PDGF/p-15 和 PDGF/AC-100 的联合使用中发现了显著差异(p<0.05)。
我们的研究结果表明,PDGF 与合成肽在分化和增殖中表现出协同作用。这些协同作用导致成骨样细胞的早期显著钙化(p<0.05)。我们建议将合成肽和 PDGF 联合作为加速骨愈合或涂层骨合成材料的潜在临床方法。