Potential Role of BMP7 in Regenerative Dentistry

Abstract

In recent years, the field of regenerative dentistry has garnered considerable attention for its focus on restoring and renewing damaged dental tissue. This narrative review explores the potential of bone morphogenetic protein 7 (BMP7) and its diverse applications in the regeneration of dental tissue. Recently, significant efforts have been made to understand BMP7's role in advancing regenerative dentistry. Amongst the various signalling molecules investigated for their regenerative capabilities, BMP7 emerges as a pivotal candidate, demonstrating the ability to stimulate the regeneration of dental pulp, periodontal, craniofacial, and alveolar bone tissues for dental implant placement. Whilst BMP7 exhibits significant promise as a therapeutic agent in regenerative dentistry, further research and clinical trials are necessary to fully unlock its potential and optimise its clinical effectiveness in addressing diverse dental and craniofacial conditions. This review highlights BMP7's substantial potential and emphasises the ongoing need for continued research to effectively harness its clinical utility in diverse dental and craniofacial contexts.

Keywords: BMP7; Bone morphogenetic protein 7; Bone regeneration; Oral tissue regeneration; Pulp regeneration; Regenerative dentistry.

Fig. 1

Structure of BMP7. The BMP7 protein is composed of 431 amino acids and consists of an N-terminal 29–amino acid signal peptide, a 263–amino acid propeptide for folding and secretion, and a 139–amino acid C-terminal mature peptide that contains the 7-cysteine domain of the transforming growth factor–beta protein family.

Fig. 2

BMP7 signalling pathway. BMP7 signalling is initiated in the target cells by binding to the specific type 2 BMP receptors on the cell membrane, forming a heterotetrameric complex, which then phosphorylates type I BMP receptors and initiates both the canonical and noncanonical signalling pathways. In the canonical pathway, BMPR2 activation triggers the phosphorylation of Smad-1/5/8, forming a complex with Smad-4, which then translocates the signal into the cell and regulates gene expression. In the noncanonical pathway or Smad-independent signalling pathway, several signalling pathways (such as MAP kinase pathways) are activated. Ultimately, these pathways collectively affect different transcription factors and contribute to regulating gene expression.

Fig. 3

Significance of BMP7 during tooth development. This figure illustrates the pivotal role of BMP7 in the process of tooth development. The main stages of tooth development, including the initiation, bud, cap, and bell stages, are highlighted. During the cap stage, BMP7 is expressed in the epithelium and the mesenchyme. In the early bell stage, BMP7 expression decreases and is primarily localised in the dental papilla. BMP7 plays an important role in determining tooth morphology and controlling the differentiation of dental tissues. At P0, during the initiation of molar tooth mineralisation, BMP7 signalling in the odontoblast, independently of BMP2 signalling, regulates the balance between the canonical and noncanonical Wnt signalling pathways, thereby initiating tooth mineralisation.

Fig. 4

The role of BMP7 in endogenous pulp regeneration. This figure provides a schematic representation of the multifaceted role of BMP7 in endogenous pulp regeneration. The regenerative process initiates when the dental pulp undergoes damage due to external factors, trauma, or infection. In response to these triggers, cells within the damaged pulp release BMP7, a signalling protein, which in turn activates the resident dental stem cells. These activated stem cells under the influence of BMP7 exhibit increased adhesion, spreading, and migration capabilities, leading to their differentiation into odontoblasts. These newly formed odontoblasts play an important role in the formation of dentin, the hard tissue within the tooth. Concurrently, BMP7 also stimulates the migration of endothelial cells within the dental pulp, facilitating the process of vascularisation.

Fig. 5

The function of BMP7 in periodontal tissue regeneration. This figure illustrates the communal regenerative effects of BMP7 and bone marrow–derived mesenchymal stem cells (BMSCs) in periodontal tissue repair. In diseased tooth, the periodontal pocket BMSCs treated with BMP7 stimulate the osteogenic differentiation of the BMSCs, thereby promoting the formation of new bone and periodontal tissues. This dynamic interaction between BMP7 and BMSCs enhances periodontal tissue regeneration, promoting promising directions for periodontal therapy.

Fig. 6

The role of BMP7 in alveolar bone regeneration. This figure illustrates the role of BMP7 in the alveolar bone regeneration process. BMP7, a potent osteogenic growth factor, is depicted as a signalling molecule released in response to bone injury or remodelling stimulus. BMP7 activates the osteoprogenitor cells, promoting them to differentiate into osteoblasts (bone-forming cells). Osteoblasts are cells responsible for creating and depositing bone matrix, resulting in the formation of new bone tissue. Over time, the newly formed bone matrix undergoes mineralisation. BMP7 also has a complex interaction with osteoclasts (bone-resorbing cells). BMP7 can indirectly stimulate osteoclast activity through various mechanisms. The equilibrium between osteogenesis and osteoclast-derived bone resorption results in the fine-tuned remodelling of the alveolar bone. In summary, BMP7 plays a pivotal role in alveolar bone regeneration, making it a promising candidate for therapeutic strategies aimed at enhancing the success of dental implants and treating bone defects in the oral and maxillofacial region.