Osteogenin, and related
bone morphogenetic proteins, induce endochondral bone differentiation through a cascade of events which include formation of cartilage,
hypertrophy and calcification of the cartilage, vascular invasion, differentiation of osteoblasts, and formation of bone. These events have been studied in a postnatal model of bone development in rodents. Information concerning the morphogenetic potential of
osteogenin in primates is a prerequisite for potential clinical application in man. The efficacy of allogeneic
osteogenin in primates was investigated in both extraskeletal and skeletal sites in 19-Chacma baboons (Papio ursinus).
Osteogenin was isolated from demineralized baboon bone matrix and purified by chromatography on
heparin-Sepharose,
hydroxyapatite, and
Sephacryl S-200.
Protein fractions with a molecular mass range of 26-42 kDa induced cartilage and bone differentiation in the subcutaneous space of rats. Final purification to homogeneity was obtained by electroendosmotic elution from a preparative
sodium dodecyl sulphate (SDS)
polyacrylamide gel, resulting in a single band on a SDS-
polyacrylamide gel with an apparent molecular mass of 30-34 kDa, with
biological activity in rats. The osteoinductive potential of
osteogenin in primates was tested first in intramuscular sites in baboons and found to be active. The bone regeneration potential was investigated in nonhealing calvarial defects surgically prepared in adult male baboons. Baboon
osteogenin induced complete regeneration of the cranial
wound. These findings in adult primates establish a primary role for
osteogenin in initiation and promotion of osteogenesis, and imply a potential therapeutic application based on cell biology of extracellular matrix-cell interactions.