Takagi K, Urist M R
Ann Surg. 1982 Jul;196(1):100-9. doi: 10.1097/00000658-198207000-00020.
Trephine defects in the adult rat skull 0.8 cm in diameter, which do not spontaneously heal, were filled with a bovine bone morphogenetic protein (BMP) fraction. The defects healed not only by bony ingrowth from the trephine rim, but also by proliferation of pervascular mesenchymal-type cells (pericytes) of the dura mater. Under the influence of BMP, dural pericytes differentiated into chondroid and woven bone. Between three and four weeks postimplantation, sinusoids formed and the woven bone remodelled into lamellar bone. Concurrently, blood-borne bone marrow cells colonized the bone deposits, and the diploe were restored. Demonstrating that it is soluble in interstitial fluid, and diffusible across a nucleopore membrane (which isolated the bony margins of the skull), BMP induced new bone formation in the underlying dura and complete repair of the defect. The response of the dura to the BMP fraction produced more new bone than the response to allogeneic bone matrix. The BMP-induced repair was dose dependent; the quantity of new bone was proportional to the dose of the implanted BMP.
在成年大鼠颅骨上制造直径0.8厘米且不会自发愈合的环钻缺损，用牛骨形态发生蛋白（BMP）组分填充。缺损不仅通过环钻边缘的骨向内生长而愈合，还通过硬脑膜血管周围间充质型细胞（周细胞）的增殖而愈合。在BMP的影响下，硬脑膜周细胞分化为类软骨和编织骨。植入后三到四周，形成血窦，编织骨重塑为板层骨。同时，血源性骨髓细胞定植于骨沉积物，板障得以恢复。BMP可溶于组织液并能穿过核孔膜（该膜隔离了颅骨的骨边缘），这表明BMP可诱导硬脑膜下新骨形成并使缺损完全修复。硬脑膜对BMP组分的反应比同种异体骨基质产生更多新骨。BMP诱导的修复呈剂量依赖性；新骨量与植入BMP的剂量成正比。
