Osteogenic differentiation cues of the bone morphogenetic protein-9 (BMP-9) and its recent advances in bone tissue regeneration

Mater Sci Eng C Mater Biol Appl. 2021 Jan;120:111748. doi: 10.1016/j.msec.2020.111748. Epub 2020 Nov 27.


Bone regeneration using bioactive molecules and biocompatible materials is growing steadily with the advent of the new findings in cellular signaling. Bone Morphogenetic Protein (BMP)-9 is a considerably recent discovery from the BMP family that delivers numerous benefits in osteogenesis. The Smad cellular signaling pathway triggered by BMPs is often inhibited by Noggin. However, BMP-9 is resistant to Noggin, thus, facilitating a more robust cellular differentiation of osteoprogenitor cells into preosteoblasts and osteoblasts. This review encompasses a general understanding of the Smad signaling pathway activated by the BMP-9 ligand molecule with its specific receptors. The robust osteogenic cellular differentiation cue provided by BMP-9 has been reviewed from a bone regeneration perspective with several in vitro as well as in vivo studies reporting promising results for future research. The effect of the biomaterial, chosen in such studies as the scaffold or carrier matrix, on the activity of BMP-9 and subsequent bone regeneration has been highlighted in this review. The non-viral delivery technique for BMP-9 induced bone regeneration is a safer alternative to its viral counterpart. The recent advances in non-viral BMP-9 delivery have also highlighted the efficacy of the protein molecule at a low dosage. This opens a new horizon as a more efficient and safer alternative to BMP-2, which was prevalent among clinical trials; however, BMP-2 applications have reported its downsides during bone defect healing such as cystic bone formation.

Keywords: Bone morphogenetic protein (BMP); Bone regeneration; Cell signaling; Non-viral delivery; Scaffold; Smad.

Publication types

  • Review

MeSH terms

  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins
  • Bone Regeneration
  • Cell Differentiation
  • Cues
  • Growth Differentiation Factor 2*
  • Osteoblasts
  • Osteogenesis*


  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins
  • Growth Differentiation Factor 2