Bone morphogenetic protein 2 explained

Bone morphogenetic protein 2 or BMP-2 belongs to the TGF-β superfamily of proteins.[1]

Function

BMP-2 like other bone morphogenetic proteins,[2] plays an important role in the development of bone and cartilage. It is involved in the hedgehog pathway, TGF beta signaling pathway, and in cytokine-cytokine receptor interaction. It is also involved in cardiac cell differentiation and epithelial to mesenchymal transition.

Like many other proteins from the BMP family, BMP-2 has been demonstrated to potently induce osteoblast differentiation in a variety of cell types.[3]

BMP-2 may be involved in white adipogenesis[4] [5] and may have metabolic effects.

Interactions

Bone morphogenetic protein 2 has been shown to interact with BMPR1A.[6] [7] [8] [9]

Clinical use and complications

Bone morphogenetic protein 2 is shown to stimulate the production of bone.[10] [11] Recombinant human protein (rhBMP-2) is currently available for orthopaedic usage in the United States.[12] Implantation of BMP-2 is performed using a variety of biomaterial carriers ("metals, ceramics, polymers, and composites"[13]) and delivery systems ("hydrogel, microsphere, nanoparticles, and fibers"). While used primarily in orthopedic procedures such as spinal fusion,[14] [15] BMP-2 has also found its way into the field of dentistry.[16] [17] [18]

The use of dual tapered threaded fusion cages and recombinant human bone morphogenetic protein-2 on an absorbable collagen sponge obtained and maintained intervertebral spinal fusion, improved clinical outcomes, and reduced pain after anterior lumbar interbody arthrodesis in patients with degenerative lumbar disc disease. As an adjuvant to allograft bone or as a replacement for harvested autograft, bone morphogenetic proteins (BMPs) appear to improve fusion rates after spinal arthrodesis in both animal models and humans, while reducing the donor-site morbidity previously associated with such procedures.

A study published in 2011 noted "reports of frequent and occasionally catastrophic complications associated with use of [BMP-2] in spinal fusion surgeries", with a level of risk far in excess of estimates reported in earlier studies.[19] [20] An additional review by Agrawal and Sinha of BMP-2 and its common delivery systems in early 2016 showed how "problems like ectopic growth, lesser protein delivery, [and] inactivation of the protein" reveal a further need "to modify the available carrier systems as well as explore other biomaterials with desired properties."

Further reading

Notes and References

  1. Sampath TK, Coughlin JE, Whetstone RM, Banach D, Corbett C, Ridge RJ, Ozkaynak E, Oppermann H, Rueger DC . Bovine osteogenic protein is composed of dimers of OP-1 and BMP-2A, two members of the transforming growth factor-beta superfamily . J. Biol. Chem. . 265 . 22 . 13198–205 . August 1990 . 10.1016/S0021-9258(19)38285-7 . 2376592 . free .
  2. Chen D, Zhao M, Mundy GR . Bone morphogenetic proteins . Growth Factors . 22 . 4 . 233–41 . December 2004 . 15621726 . 10.1080/08977190412331279890 . 22932278 .
  3. Marie PJ, Debiais F, Haÿ E . Regulation of human cranial osteoblast phenotype by FGF-2, FGFR-2 and BMP-2 signaling . Histol. Histopathol. . 17 . 3 . 877–85 . 2002 . 12168799 . 10.14670/HH-17.877.
  4. Jin W, Takagi T, Kanesashi SN, Kurahashi T, Nomura T, Harada J, Ishii S . Schnurri-2 controls BMP-dependent adipogenesis via interaction with Smad proteins . Developmental Cell . 10 . 4 . 461–71 . April 2006 . 16580992 . 10.1016/j.devcel.2006.02.016 . free .
  5. Blázquez-Medela AM, Jumabay M, Boström KI . Beyond the bone: Bone morphogenetic protein signaling in adipose tissue . Obesity Reviews . 20 . 5 . 648–658 . January 2019 . 30609449 . 6447448 . 10.1111/obr.12822 .
  6. Nickel J, Dreyer MK, Kirsch T, Sebald W . The crystal structure of the BMP-2:BMPR-IA complex and the generation of BMP-2 antagonists . J Bone Joint Surg Am . 83-A Suppl 1 . Pt 1 . S7–14 . 2001 . 11263668 .
  7. Kirsch T, Nickel J, Sebald W . Isolation of recombinant BMP receptor IA ectodomain and its 2:1 complex with BMP-2 . FEBS Lett. . 468 . 2–3 . 215–9 . February 2000 . 10692589 . 10.1016/S0014-5793(00)01214-X . 30068719 . free . 2000FEBSL.468..215K .
  8. Kirsch T, Nickel J, Sebald W . BMP-2 antagonists emerge from alterations in the low-affinity binding epitope for receptor BMPR-II . EMBO J. . 19 . 13 . 3314–24 . July 2000 . 10880444 . 313944 . 10.1093/emboj/19.13.3314 .
  9. Gilboa L, Nohe A, Geissendörfer T, Sebald W, Henis YI, Knaus P . Bone morphogenetic protein receptor complexes on the surface of live cells: a new oligomerization mode for serine/threonine kinase receptors . Mol. Biol. Cell . 11 . 3 . 1023–35 . March 2000 . 10712517 . 14828 . 10.1091/mbc.11.3.1023 .
  10. Urist MR . Bone: formation by autoinduction . Science . 150 . 3698 . 893–9 . 1965 . 5319761 . 10.1126/science.150.3698.893 . Marshall R. Urist . 1965Sci...150..893U . 83951938 .
  11. Geiger M, Li RH, Friess W . Collagen sponges for bone regeneration with rhBMP-2 . Adv. Drug Deliv. Rev. . 55 . 12 . 1613–29 . November 2003 . 14623404 . 10.1016/j.addr.2003.08.010 .
  12. Khan SN, Lane JM . The use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in orthopaedic applications . Expert Opin Biol Ther . 4 . 5 . 741–8 . May 2004 . 15155165 . 10.1517/14712598.4.5.741 . 45699304 .
  13. A review on carrier systems for bone morphogenetic protein-2 . Journal of Biomedical Materials Research Part B: Applied Biomaterials . Agrawal, V . Sinha, M. . Early View . 4 . 904–925 . 2016 . 10.1002/jbm.b.33599 . 26728994.
  14. Burkus JK, Gornet MF, Schuler TC, Kleeman TJ, Zdeblick TA . Six-year outcomes of anterior lumbar interbody arthrodesis with use of interbody fusion cages and recombinant human bone morphogenetic protein-2 . J Bone Joint Surg Am . 91 . 5 . 1181–9 . May 2009 . 19411467 . 10.2106/JBJS.G.01485 .
  15. Subach BR, Haid RW, Rodts GE, Kaiser MG . Bone morphogenetic protein in spinal fusion: overview and clinical update . Neurosurg Focus . 10 . 4 . 1–6 . 2001 . 16732630 . 10.3171/foc.2001.10.4.4 . free .
  16. Allegrini S, Yoshimoto M, Salles MB, König B . Bone regeneration in rabbit sinus lifting associated with bovine BMP . Journal of Biomedical Materials Research Part B: Applied Biomaterials. 68 . 2 . 127–31 . February 2004 . 14737759 . 10.1002/jbm.b.20006 . free .
  17. Schlegel KA, Thorwarth M, Plesinac A, Wiltfang J, Rupprecht S . Expression of bone matrix proteins during the osseus healing of topical conditioned implants: an experimental study . Clinical Oral Implants Research . 17 . 6 . 666–72 . December 2006 . 17092225 . 10.1111/j.1600-0501.2006.01214.x .
  18. Schliephake H, Aref A, Scharnweber D, Bierbaum S, Roessler S, Sewing A . Effect of immobilized bone morphogenic protein 2 coating of titanium implants on peri-implant bone formation . Clinical Oral Implants Research . 16 . 5 . 563–9 . October 2005 . 16164462 . 10.1111/j.1600-0501.2005.01143.x .
  19. News: Medtronic's spinal fusion product shown to be harmful in bold review by medical journal and its Stanford editors . Inside Stanford Medicine . Stanford School of Medicine . Richter R . 2011-06-28 . 2012-06-25 . dead . https://web.archive.org/web/20120423014645/http://med.stanford.edu/ism/2011/june/carragee-spine-0628.html . 2012-04-23 .
  20. Carragee EJ, Hurwitz EL, Weiner BK . A critical review of recombinant human bone morphogenetic protein-2 trials in spinal surgery: emerging safety concerns and lessons learned . Spine J . 11 . 6 . 471–91 . June 2011 . 21729796 . 10.1016/j.spinee.2011.04.023 . dead . https://web.archive.org/web/20111110075333/http://www.spine.org/Documents/TSJJune2011_Carragee_etal_CriticalRev.pdf . 2011-11-10 .

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