Effect of Extracellular Matrix in BMP-Induced Chondro- and Osteogenesis

点击翻译按钮获取中文摘要

Bone morphogenetic proteins (BMPs) stimulate immature mesenchymal cells to create a process similar to endochondral ossification when they are subcutaneously implanted with insoluble bone matrix (IBM). However, by testing various carriers other than IBM,we found that BMP-induced cell-differentiation is highly dependent on the nature of carrier. This situation further led us to study the effect of the carriers using at least seven different carriers other than IBM.These BMP-carriers were classified into three types : fiber-, particle-and block-types.(1) The fiber-type includes fibrous collagen membrane and fibrous glass membrane (FGM). (2) The particle-type : collagen beads, porous particles of hydroxyapatite (PPHAP) and solid particles of hydroxyapatite, and (3) the block-type : porous blocks of hydroxyapatite and honeycomb-shaped hydroxyapatite. Recombinant human BMP-2 (rhBMP-2, a kind gift from Yamanouchi Co.) and the partially purified BMP (S300 fraction) which contains all the active BMPs (BMPs cocktail) were used as the source of BMPs. Each BMP-combined carrier induced unique pattern of bone and cartilage formation. To give typical examples, a combination of S300 and FGM (with a fiber diameter of 1mum and thickness of 0.6 mm) induced exclusively cartilage inside the membrane. In contrast, PPHAP/S300 implants induced bone formation that directly followed fibrous tissue formation within the pores of PPHAP,without any detectable cartilage formation. It was concluded that continuous pores structure such as PPHAP creates a space sufficient for vasculature, while the tight network of FGM (1 mum exclusion size) provides immature cells with space for penetrating into the membrane, but not for vascular formation. Thus, vasculature-forming or refusing structure is one of the key geometric factors of BMP-carrier for bone and cartilage induction.