Bone morphogenetic protein

Bone Morphogenetic Proteins (BMPs) are a group of growth factors and cytokines known for their ability to induce the formation of bone and cartilage.

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Types

Originally, seven such proteins were discovered. Of these, six of them (BMP2 through BMP7) belong to the Transforming growth factor beta superfamily of proteins.

Since then, thirteen more BMPs have been discovered, bringing the total to twenty.

Function

BMPs interact with specific receptors on the cell surface, referred to as bone morphogenetic protein receptors (BMPRs).

Signal transduction through BMPRs results in mobilization of members of the SMAD family of proteins. The signaling pathways involving BMPs, BMPRs and Smads are important in the development of the heart, central nervous system, and cartilage, as well as post-natal bone development.

They have an important role during embryonic development on the embryonic patterning and early skeletal formation. As such, disruption of BMP signaling can affect the body plan of the developing embryo. For example, BMP4 and its inhibitors noggin and chordin help regulate polarity of the embryo (i.e. back to front patterning).

Mutations in BMPs and their inhibitors (such as sclerostin) are associated with a number of human disorders which affect the skeleton.

Several BMPs are also named 'cartilage-derived morphogenetic proteins' (CDMPs), while others are referred to as 'growth differentiation factors' (GDFs).

Discovery

The seminal paper reporting the initial discovery of bone morphogenetic protein activity was published in 1965 by Marshall R. Urist in Science.^[1]

List of Bone Morphogenetic Proteins

Clinical uses

Members of the BMP family are potentially useful as therapeutics in areas such as spinal fusion. BMP-2 and BMP-7 have been shown in clinical studies to beneficial in the treatment of a variety of bone-related conditions including delayed union and non-union. BMP-2 and BMP-7 have received Food and Drug Administration (FDA) approval for human clinical uses. At between $6000 and $10,000 for a typical treatment, BMPs can be costly compared with other techniques such as bone grafting. However, this cost is often far less than the costs required with orthopaedic revision in multiple surgeries.

BMP-7 has also recently found use in the treatment of chronic kidney disease (CKD). BMP-7 has been shown in murine animal models to reverse the loss of glomeruli due to sclerosis. Curis has been in the forefront of developing BMP-7 for this use. In 2002, Curis licensed BMP-7 to Ortho Biotech Products, a subsidiary of Johnson & Johnson.

References

1. ^ Urist, Marshall R. (1965). "Bone: formation by autoinduction". Science 12:150 (698): 893–899. PMID 5319761. available at JSTOR