Part:BBa_K5374008

BMP-4 (Bone Morphogenetic Protein-4).BMP-4 is a signaling protein that plays a key role in bone form

BMP-4 belongs to the TGF-β (Transforming Growth Factor-Beta) family and is essential for bone regeneration and cartilage formation. It stimulates the differentiation of mesenchymal stem cells into osteoblasts, promoting bone and cartilage development, making it critical for tissue engineering applications.

BMP-4 is a member of the TGF-β (Transforming Growth Factor-Beta) superfamily, primarily involved in bone and cartilage development. It plays a crucial role in osteogenesis by inducing the differentiation of mesenchymal stem cells into osteoblasts, the bone-forming cells. This protein is critical during embryonic development for the formation of bones, cartilage, and teeth, and has widespread implications in tissue homeostasis and repair.

Biological Functions

• Bone Formation: BMP-4 signals through Smad proteins and other pathways to stimulate the differentiation of osteoprogenitor cells into osteoblasts, which are responsible for depositing bone matrix.
• Cartilage and Tissue Repair: BMP-4 plays a pivotal role in the regeneration of cartilage and repair of tissue defects, making it a valuable tool for tissue engineering and bone repair therapies.
• Developmental Role: In early development, BMP-4 regulates processes like gastrulation, limb formation, and neural development, ensuring proper embryonic growth and organogenesis.

Recombinant Production

BMP-4 is often produced recombinantly in E. coli or mammalian cell systems for therapeutic and research purposes. The protein's structure consists of two chains that form a homodimer, stabilized by disulfide bonds, which are essential for its bioactivity. During recombinant production, sequence modifications and codon optimization are critical for maintaining the protein’s correct folding and activity.

Applications

BMP-4’s ability to promote bone and cartilage growth makes it a key target in:

• Bone Repair and Regeneration: Used in clinical therapies for conditions such as bone fractures and spinal fusions.
• Tissue Engineering: Integrating BMP-4 into biomaterials like collagen hydrogels to promote osteogenesis and facilitate bone healing in synthetic biology.

Design Considerations

When designing a recombinant BMP-4 expression system:

• Codon Optimization: Codon usage must be adapted for the expression host (e.g., E. coli).
• Post-Translational Modifications: Ensuring the correct formation of disulfide bonds is crucial to maintain bioactivity.

References

1. Wu, M., Chen, G., & Li, Y.-P. (2016). TGF-β and BMP signaling in osteoblast, skeletal development, and bone formation, homeostasis and disease. Bone Research, 4, 16009. https://doi.org/10.1038/boneres.2016.9
2. Reddi, A. H. (2005). BMPs: From bone morphogenetic proteins to body morphogenetic proteins. Cytokine & Growth Factor Reviews, 16(3), 249–250. https://doi.org/10.1016/j.cytogfr.2005.02.003
3. Wei, G., Jin, Y., Giannobile, W. V., & Ma, P. X. (2006). The enhancement of osteogenesis by nano-fibrous scaffolds incorporating rhBMP-7 nanospheres. Biomaterials, 27(36), 5976–5983. https://doi.org/10.1016/j.biomaterials.2006.08.008

Sequence and Features

Assembly Compatibility:

• 10
  INCOMPATIBLE WITH RFC[10]

  Illegal PstI site found at 184
  Illegal PstI site found at 265
  
• 12
  INCOMPATIBLE WITH RFC[12]

  Illegal NheI site found at 61
  Illegal PstI site found at 184
  Illegal PstI site found at 265
  
• 21
  COMPATIBLE WITH RFC[21]
• 23
  INCOMPATIBLE WITH RFC[23]

  Illegal PstI site found at 184
  Illegal PstI site found at 265
  
• 25
  INCOMPATIBLE WITH RFC[25]

  Illegal PstI site found at 184
  Illegal PstI site found at 265
  
• 1000
  COMPATIBLE WITH RFC[1000]