Discovery
For a detailed history of the discovery and isolation of bone morphogenetic proteins read "Bone Morphogenetic Proteins: an Unconventional Approach to Isolation of First Mammalian Morphogens" in Cytokine & Growth Factor Reviews. or "Bone morphogenetic proteins in tissue engineering: the road from laboratory to the clinic" in Journal of Tissue Engineering and Regenerative Medicine.
From the time of Hippocrates it has been known that bone has considerable potential for regeneration and repair. Nicholas Senn, a surgeon at Rush Medical College in Chicago, described the utility of antiseptic decalcified bone implants in the treatment of osteomyelitis and certain bone deformities. Pierre Lacroix proposed that there might be a hypothetical substance, osteogenin, that might initiate bone growth.
The biological basis of bone morphogenesis was shown by Marshall R. Urist. Urist made the key discovery that demineralized, lyophilized segments of bone induced new bone formation when implanted in muscle pouches in rabbits. This seminal discovery was published in 1965 by Urist in Science. Marshall Urist proposed the name "Bone Morphogenetic Protein" in the scientific literature in the Journal of Dental Research in 1971. Marshall Urist died on February 4, 2001. A tribute to him and his research was written in the Journal of Bone and Joint Surgery.
Bone induction is a sequential multistep cascade. The key steps in this cascade are chemotaxis, mitosis, and differentiation. Early studies by Hari Reddi unraveled the sequence of events involved in bone matrix-induced bone morphogenesis. On the basis of the above work, it seemed likely that morphogens were present in the bone matrix. Using a battery of bioassays for bone formation, a systematic study was undertaken to isolate and purify putative bone morphogenetic proteins.
A major stumbling block to purification was the insolubility of demineralized bone matrix. To overcome this hurdle, Hari Reddi and Kuber Sampath used dissociative extractants, such as 4M guanidine HCL, 8M Urea, or 1% SDS. The soluble extract alone or the insoluble residues alone were incapable of new bone induction. This work suggested that the optimal osteogenic activity requires a synergy between soluble extract and the insoluble collagenous substratum. It not only represented a significant advance toward the final purification of bone morphogenetic proteins (BMPs) by the Reddi laboratory, but ultimately also enabled the cloning of BMPs by John Wozney and colleagues at Genetics Institute.
Read more about this topic: Bone Morphogenetic Protein
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