Bone morphogenetic protein

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Overview

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

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


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 involved 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 integrity 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

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

External links

  • BMP: The What and the Who
  • Bone+Morphogenetic+Proteins at the US National Library of Medicine Medical Subject Headings (MeSH)
  • Chen, Di, Zhao, Ming, and Mundy, Gregory R. (2004). "Bone Morphogenetic Proteins". Growth Factors. 22 (4): 233–241. PMID 15621726.
  • Cheng H, Jiang W, Phillips F, Haydon R, Peng Y, Zhou L, Luu H, An N, Breyer B, Vanichakarn P, Szatkowski J, Park J, He T (2003). "Osteogenic activity of the fourteen types of human bone morphogenetic proteins (BMPs)". J Bone Joint Surg Am. 85-A (8): 1544–52. PMID 12925636. link
  • http://www.zycalbio.com

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