Bone morphogenetic protein

From Wikipedia, the free encyclopedia

Bone Morphogenetic Proteins (BMPs) are group of growth factors known for their ability to induce the formation of bone and cartilage. Originally, seven such proteins were discovered. Of these, six of them BMP2 through BMP7 belong to the TGF-β (Transforming Growth Factor-beta) superfamily of proteins. Since then, several more BMP's have been discovered.

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, specifically SMAD1, SMAD5 and SMAD8. 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 forming. As such disruption of BMP signaling can affect the body plan of the developing embryo. For example BMP4 and its inhibitors noggin and chordin play a role in determining the back and front of the embryo. Mutations of other BMPs and inhibitors of BMPs (such as sclerostin) are associated with a number of human disorders affecting the skeleton. There are sixteen reported bone morphogenetic proteins, some are also named as cartilage-derived morphogenetic proteins (CDMPs) and growth differentiation factors (GDFs).BMP1 has a novel protein structure.

1 Discovery
2 List of Bone Morphogenetic Proteins
3 Uses
4 References
- 4.1 General references
5 External links

[edit] Discovery

The seminal paper reporting the initial discovery of bone morphogenetic protein activity was published in 1965 by Marshall R. Urist in Science.<ref>Urist, Marshall R. (1965). "Bone: formation by autoinduction". Science 12:150 (698): 893–899. PMID 5319761. available at JSTOR</ref>

[edit] List of Bone Morphogenetic Proteins

BMP	Known functions	Gene Locus
BMP1	*BMP1 does not belong to the TGF-β family of proteins. It is a metalloprotease that acts on procollagen I, II, and III. It is involded in cartilage development.	Chromosome: 8; Location: 8p21
BMP2	Acts as a disulfide-linked homodimer and induces bone and cartilage formation. It is a candidate as a retinoid mediator. Plays a key role in osteoblast differentiation.	Chromosome: 20; Location: 20p12
BMP3	Induces bone formation	Chromosome: 14; Location: 14p22
BMP4	Regulates the formation of teeth, limbs and bone from mesoderm. It also plays a role in fracture repair.	Chromosome: 14; Location: 14q22-q23
BMP5	Performs functions in cartilage development.	Chromosome: 6; Location: 6p12.1
BMP6	Plays a role in joint integerity in adults.	Chromosome: 6; Location: 6p12.1
BMP7	Plays a key role in osteoblast differentiation. It also induces the production of SMAD1. Also key in renal development and repair.	Chromosome: 20; Location: 20q13
BMP8a	Involved in bone and cartilage development	Chromosome: 1; Location: 1p35-p32
BMP8b	Expressed in the hippocampus.	Chromosome: 1; Location: 1p35-p32
BMP10	May play a role in the trabeculation of the embryonic heart.	Chromosome: 2; Location: 2p14
BMP15	May play a role in oocyte and follicular development.	Chromosome: X; Location: Xp11.2

[edit] Uses

Members of the BMP family are potentially useful as therapeutics in areas such as spinal fusion. BMP-2 has been shown in clinical studies to be of use in the treatment of a variety of bone-related conditions. BMP-2 and BMP-7 have received Food and Drug Administration (FDA) approval for human clinical uses. One drawback of BMP's is their very high cost, which can be between $6000 and $10,000 for a typical treatment.

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.