BMPS INDUCE DIRECT BONE-FORMATION IN ECTOPIC SITES INDEPENDENT OF THEENDOCHONDRAL OSSIFICATION INVIVO

Bone formation in vivo occurs via two major processes, one of which de pends on pre-existing cartilage, and the other does not. Bone morphoge netic proteins (BMPs) have been suggested to induce cartilage formatio n from non-skeletogenic mesenchymal cell population, which results in osteogenesis through the endochondral sequence. In the present study w e examined if BMPs could cause direct bone formation independent of pr e-existing cartilage using bovine fibrous collagen membrane (FCM) as a carrier for BMPs. Bovine metatarsal bone was extracted in 4 M guanidi ne HCl and BMPs were partially purified through the hydroxyapatite chr omatography and the Heparin-Sepharose CL6B chromatography. The carrier was loaded with BMPs and then implanted in Wistar rats subcutaneously . The implants were fixed together with surrounding tissue every week after implantation and processed for von Kossa stain, immunohistochemi stry, and electron microscopy. The phenotypes of bone and cartilage we re identified histologically and immunohistochemically using antibodie s against type I and type II collagen. Cartilage and bone were indepen dently induced by 2 weeks. The bone formed directly on the collagen su bstrate of FCM without pre-existing cartilage. Calcification occurred in the carrier as well as the cartilage and bone matrix. The present s tudy suggests that the BMPs induce osteogenesis in vivo independent of the endochondral sequence.