Blanquaert F, Barritault D, Saffar J L, Josefonvicz J, Caruelle J P
Laboratoire CRRET, INSERM CJF 90014, Université Paris XII-Val de Marne, Créteil.
Ann Endocrinol (Paris). 1994;55(2):121-3.
Several Heparin-Binding Growth Factors (HBGFs) are known to play an important role in bone repair. When osseous tissue is injured, an important increase of protease activities and a massive release of HBGFs occur. The local increase in HBGFs content at the wounded site, produced by a release of this factors from cells implicated in haemostasis and inflammatory reaction and from extracellular matrix associated heparan sulfate proteoglycans (HSPGs), seems to be a crucial step in bone healing. The proteolysis associated with the tissue injury probably limits the growth factors activities at the wound site. In order to define the bone healing potential of molecules that would be able to protect HBGFs against proteolytic activation, we studied the effect of derived dextrans, named carboxymethyl-benzylamide-sulfonated dextrans (CMDBS), behaving as heparan like molecules, in 5 mm in diameter skull trepaned defects in young adult rats. In this model CMDBS induced an important bone regeneration in a dose dependent manner while controls were not repaired. In CMDBS treated animals the defects were repaired and contained a tissue of normal appearance; in several treated animals the sagittal suture, initially removed by the trephination, was restored. This remarkable bone healing potential of CMDBS may result from the capacity to protect the endogenous HBGFs from proteolysis and to modulate their biological activities, in a similar manner to that observed for fibroblast growth factors and HSPGs. CMDBS represent a new form of bone healing agents, which have the advantage of being produced by a controlled chemical synthesis, and of avoiding the use of exogenous growth factors because of their capacity to enhance the bone healing potential of the endogenous growth factors.
已知几种肝素结合生长因子（HBGFs）在骨修复中起重要作用。当骨组织受损时，蛋白酶活性会显著增加，同时HBGFs会大量释放。止血和炎症反应相关细胞以及细胞外基质相关硫酸乙酰肝素蛋白聚糖（HSPGs）释放这些因子，导致伤口部位HBGFs含量局部增加，这似乎是骨愈合的关键步骤。与组织损伤相关的蛋白水解作用可能会限制伤口部位生长因子的活性。为了确定能够保护HBGFs免受蛋白水解激活的分子的骨愈合潜力，我们研究了一种名为羧甲基苄酰胺磺化葡聚糖（CMDBS）的葡聚糖衍生物的作用，它表现得像类肝素分子，作用于成年幼鼠直径5毫米的颅骨钻孔缺损处。在这个模型中，CMDBS以剂量依赖的方式诱导了重要的骨再生，而对照组则没有修复。在接受CMDBS治疗的动物中，缺损得到修复，并且包含外观正常的组织；在几只接受治疗的动物中，最初因钻孔而移除的矢状缝得以恢复。CMDBS这种显著的骨愈合潜力可能源于其保护内源性HBGFs免受蛋白水解并调节其生物活性的能力，这与成纤维细胞生长因子和HSPGs的情况类似。CMDBS代表了一种新型的骨愈合剂，其优点是通过可控的化学合成生产，并且由于其能够增强内源性生长因子的骨愈合潜力，从而避免了使用外源性生长因子。
