Bone morphogenetic protein ( BMP ) is a group of growth factors also known as cytokines and as metabol- ogens. Originally discovered by their ability to induce bone and cartilage formation, BMP is now regarded as a group of important morphogenetic signals, regulating the network architecture throughout the body. The important function of BMP signals in physiology is emphasized by many roles for BMP signaling that are not regulated in pathological processes. Cancer often involves incorrect setting of BMP signaling systems. The absence of BMP signaling is, for example, an important factor in the development of colon cancer, and vice versa, excessive deactivation of BMP signaling after reflux-induced esophagitis provokes Barrett's esophagus and thus contributes to adenocarcinoma development in the gastrointestinal proximal portion. system.
Recombinant human BMPs (rhBMPs) are used in orthopedic applications such as spinal fusion, nonunions and oral surgery. rhBMP-2 and rhBMP-7 are the Food and Drug Administration (FDA) - approved for multiple uses. rhBMP-2 causes more bones to grow than other BMPs and is widely used outside labels.
Video Bone morphogenetic protein
Medical use
BMPs for clinical use were produced using recombinant DNA technology (recombinant human BMP, rhBMPs).
rhBMP is used in oral surgery. BMP-7 has also recently been found to be used in the treatment of chronic kidney disease (CKD). BMP-7 has been shown in the murine animal model to reverse the loss of glomeruli due to sclerosis. Curis has been at the forefront of developing BMP-7 for this usage. In 2002, Curis licensed BMP-7 for Ortho Biotech Products, a Johnson & amp; Johnson.
Off-label use
Although rhBMP-2 and rhBMP-7 are used in the treatment of various bone-related conditions including spinal fusion and nonunions, the risk of off-label treatment is not understood. While rhBMP is approved for specific applications (spinal lumbar fusion with anterior approach and tibia nonunions), up to 85% of all BMP use is off-label. rhBMP-2 is used extensively in other lumbar spine fusion techniques (eg, using a posterior approach, anterior or posterior cervical fusion).
Alternative to autograft in non-long bone members
In 2001, the Food and Drug Administration (FDA) approved rhBMP-7 (a.k.a. OP-1, Stryker Biotech) for the exclusion of humanitarian devices as an alternative to autograft in non-long bone members. In 2004, the release of humanitarian devices was extended as an alternative to autograft for posterolateral fusion. In 2002, rhBMP-2 (Infusion, Medtronic) was approved for anterior lumbar interbody fusions (ALIFs) with a lumbar fusion device. In 2008 it was approved to correct posterolateral lumbar pseudarthrosis, an open tibia fracture fracture with intramedullary nail fixation. In this product, BMP is sent to the site of the fracture by inserting into the bone implants, and is released gradually to allow for bone formation, as the growth stimulation by BMP should be localized and sustained for several weeks. BMP is eluted through a pure collagen matrix implanted at the site of the fracture. rhBMP-2 helps to grow bone better than other rhBMP so much more clinically used. There is a "small debate or controversy" about the effectiveness of rhBMP-2 to grow bones to achieve spinal fusion, and Medtronic earns $ 700 million in annual sales of their products.
Maps Bone morphogenetic protein
Contraindications
Bone morphogenetic protein (rhBMP) should not be used routinely in all types of anterior cervical spine fusion, such as with anterior cervical discectomy and fusion. There are reports of this therapy that cause soft tissue swelling which can in turn lead to life-threatening complications due to difficulty swallowing and pressure on the respiratory tract.
Function
BMP interacts with specific receptors on the cell surface, which are called bone morphogenetic protein receptors (BMPRs).
The transduction signal through BMPR produces the mobilization of members of the SMAD protein family. Signaling pathways involving BMP, BMPR and SMAD are essential in the development of the heart, the central nervous system, and cartilage, as well as the development of postnatal bone.
They have an important role during embryonic development on embryonal patterns and early skeletal formation. Thus, BMP signaling disorders may affect the body plan of the developing embryo. For example, BMP4 and its inhibitors noggin and chordin help regulate the embryo polarity (ie back to the front pattern). In particular BMP-4 and its inhibitors play a major role in neurulation and development of neural plates. BMP-4 suggests the ectoderm cell to develop into skin cells, but the secretion of the inhibitor by the mesoderm underlying the action of BMP-4 to allow the ectoderm to proceed on the normal development of nerve cells.
As a member of the superfamily-beta growth factor, BMP signaling regulates various embryonal patterns during fetal and embryonic development. For example, BMP signaling controls the early formation of the Mullerian duct (MD) which is a tubular structure at the early embryonic development stage and eventually becomes the female reproductive tract. BMP signals that inhibit chemistry in chicken embryos cause MD invagination disorders and inhibit epithelial thickening in MD formation areas, indicating that BMP signals play a role in early MD development. In addition, BMP signaling is involved in the formation of foregut and hindgut, gut villus pattern, and endocardial differentiation. Villi contribute to improving the effective absorption of nutrients by expanding the surface area in the small intestine. Gain or loss of BMP signaling function changes the cluster pattern and the emergence of villi in mouse intestine model. BMP signals originating from the myocardium are also involved in endocard differentiation during cardiac development. The inhibited BMP signal in the embryonic model of zebrafish leads to a strong decrease in endocardial differentiation, but has little effect on myocardial development. In addition, the Notch-Wnt-Bmp crosstalk is required for radial patterns during mouse cochlear development by means of antagonists.
Mutations in BMP and its inhibitors are associated with a number of human disorders that affect the skeleton.
Some BMPs are also named 'cartilage morphogenetic proteins' (CDMPs), while others are referred to as 'growth differentiation factors' (GDFs).
Type
Initially, seven such proteins were found. Of these, six (BMP2 through BMP7) belong to Transforming growth factor beta protein superfamily. BMP1 is a metalloprotease. Since then, thirteen BMPs have been found, bringing the total to twenty.
History
Since the time of Hippocrates it is known that bones have great potential for regeneration and repair. Nicholas Senn, a surgeon at Rush Medical College in Chicago, describes the use of an antiseptic cartilage implant in the treatment of osteomyelitis and certain bone deformities. Pierre Lacroix proposes that there may be a hypothetical substance, osteogenin, which may initiate bone growth.
The biological basis of bone morphogenesis is demonstrated by Marshall R. Urist. Urist makes a demineralized key discovery, a segment of bone lyophilization inducing new bone formation when grown in a muscle sac on a rabbit. The discovery was published in 1965 by Urist in Science. Urist proposed the name "Bone Morphogenetic Protein" in scientific literature in the Journal of Dental Research in 1971.
Bone induction is a sequential multisep cascade. The key steps in this cascade are chemotaxis, mitosis, and differentiation. Early studies by Reddi Day outline the sequence of events involved in the morphogenesis of induced matrix bones. On the basis of the above work, it appears that morphogens are present in the bone matrix. Using battery bioassays for bone formation, a systematic study was conducted to isolate and purify the alleged morphogenetic bone proteins.
A major stumbling block to purification is the inability of the demineralized bone matrix. To overcome this hurdle, Reddi Day and Kuber Sampath use dissociative extractants, such as 4M guanidine HCL, 8M urea, or 1% SDS. Self soluble extract or insoluble residue alone can not induce new bone. This work suggests that optimal osteogenic activity requires synergy between the soluble extract and the insoluble collagen substrate. This not only represents a significant advance towards the final purification of bone morphogenetic proteins by the Reddi lab, but ultimately also enables BMP cloning by John Wozney and his colleagues at the Genetics Institute.
Society
Cost
Among US $ 6000 and $ 10,000 for typical treatment, BMP can be expensive compared to other techniques such as bone grafting. However, these costs are often much lower than the costs required with orthopedic revisions in some operations.
Although there is little debate that rhBMP is clinically successful, there is controversy about its use. It is common for orthopedic surgeons to be paid for their contribution to new product development, but some surgeons responsible for Medtronic's original studies supported on the efficacy of rhBMP-2 have been accused of bias and conflicts of interest. For example, one surgeon, the lead author on four research papers, did not disclose any financial relationship with the company in three papers; he was paid more than $ 4 million by Medtronic. In another study, the lead author did not disclose any financial relationship with Medtronic; he was paid at least $ 11 million by the company. In a series of 12 publications, the author's median financial relationship to Medtronic was $ 12-16 million. In studies with more than 20 and 100 patients, one or more authors had financial ties of $ 1 million and $ 10 million, respectively. Initial clinical trials used rhBMP-2 unreported side effects associated with treatment. In 13 original industry-sponsored publications related to safety, there were zero side effects in 780 patients. It has since been revealed that potential complications may arise from use including implant removal, decline, infection, urogenital events, and retrograde ejaculation.
Based on research conducted by the Department of Family Medicine at Oregon Health and Science University, the use of BMP increased rapidly, from 5.5% of fusion cases in 2003 to 28.1% of fusion cases in 2008. The use of BMP is greater among patients with the previous. surgery and among those who have complex fusion procedures (a combination of anterior and posterior approaches, or more than 2 disk levels). Major medical complications, wound complications, and 30-day rehospitalization rates are almost identical with or without BMP. The rate of re-surgery is also very similar, even after being grouped by prior surgery or surgical complexity, and after adjusting for demographic and clinical features. On average, hospital costs adjusted for surgery involving BMP are approximately $ 15,000 more than hospital fees for fusion without BMP, although replacements under the Medicare's Diagnosis-Related Group system averaged only about $ 850 more. Significantly fewer patients who received BMP were discharged to a skilled care facility.
References
Further reading
External links
- BMP: What and Who
- BMPedia - Worm Bone Morphogenic Protein
- Bone Morphogenetic Protein at US National Library of Medicine's Medical Subject Headings (MeSH)
- Chen D, Zhao M, Mundy GR (December 2004). "Bone morphogenetic protein". Growth Factor (Chur, Switzerland) . 22 (4): 233-241. doi: 10.1080/08977190412331279890. PMIDÃ, 15621726.
- Cheng H, Jiang W, Phillips FM, Haydon RC, Peng Y, Zhou L, Luu HH, An N, Breyer B, Vanichakarn P, Szatkowski JP, Taman JY, Dia TC (August 2003). "Osteogenic activity of fourteen types of morphogenetic human bone protein (BMPs)". The Journal of Bone and Joint Surgery. American Volume . 85-A (8): 1544-52. PMID 12925636. link
Source of the article : Wikipedia
0 Comments