Bone morphogenetic protein
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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
External links
- BMP: The What and the Who
- MeSH Bone+Morphogenetic+Proteins
- 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
Cell signaling: TGF beta signaling pathway | |
|---|---|
| TGF beta superfamily of ligands | TGF beta family (TGF-β1, TGF-β2, TGF-β3) Bone morphogenetic proteins (BMP2, BMP3, BMP4, BMP5, BMP6, BMP7, BMP8a, BMP8b, BMP10 , BMP15) Growth differentiation factors (GDF1, GDF2, GDF3, GDF5, GDF6, GDF7, Myostatin/GDF8, GDF9, GDF10, GDF11, GDF15) Other (Activin A and B/Inhibin A and B, Anti-müllerian hormone, Nodal) |
| TGF beta receptors | TGFBR1: Activin type 1 receptors (ACVR1, ACVR1B, ACVR1C) - ACVRL1 - BMPR1 (BMPR1A - BMPR1B) TGFBR2: Activin type 2 receptors (ACVR2A, ACVR2B) - AMHR2 - BMPR2 TGFBR3: betaglycan |
| Transducers/SMAD | R-SMAD (SMAD1, SMAD2, SMAD3, SMAD5, SMAD9) - I-SMAD (SMAD6, SMAD7) - SMAD4 |
| Ligand Inhibitors | Cerberus - Chordin - DAN - Decorin - Follistatin - Gremlin - Lefty - LTBP1 - Noggin - THBS1 |
| Coreceptors | BAMBI - Cripto |
| Other | SARA |
Acknowledgement and Attribution Regarding Sources of Content
Some of the initial content on this page may be incorporated in part from copyleft sources in the public domain including wikis such as Wikipedia and AskDrWiki. Drug information for patients came from the The National Library of Medicine. Infectious disease information may have come from the Centers for Disease Control (CDC). Differential Diagnoses are drawn from clinicians as well as an amalgamation of 3 sources: 1.The Disease Database; 2. Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:3; 3. Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:7 .
