The current study aimed at investigating the long-term biological mechanisms governing bone regeneration in osseous defects filled with bovine bone (BB). Tooth extraction sockets were filled with BB or left unfilled for natural healing in a C57BL/6 mouse alveolar regeneration bone model (n = 12). Seven weeks later, the alveolar bone samples were analyzed histologically with hematoxylin/eosin and tartrate-resistant acid phosphatase staining. A separate group (n = 10) was used for RNA sequencing. Osteoclast inhibition was induced by zoledronic acid (ZA) administration at 2 wk postextraction in a third group (n = 28) for examination of osseous changes and cellular functions with micro–computed tomography and quantitative reverse transcription polymerase chain reaction, respectively. Histological and radiological osseous healing was observed in both BB-filled and normal-healing sockets. However, BB regenerated bone showed significant robust expression of genes associated with bone homeostasis and osteoclasts’ function. Osteoclasts’ inhibition in BB-filled sockets led to decreased bone resorption markers and reduced bone formation to a greater extent than that observed in osteoclasts’ inhibition with natural healing. BB displays long-term biologically active properties, despite a naive osseous histological appearance. These include activation of osteoclasts, which in turn promotes osseous remodeling and maturation of ossified bone.
Bibliographical noteFunding Information:
The authors also acknowledge Dr. Abedelmajeed Nasereddin (Genomic Applications Laboratory, Core Research Facility, Faculty of Medicine?Ein Kerem, Hebrew University of Jerusalem, Israel) for his support with mRNA library preparation and Dr. Yuval Nevo, Dr. Shrona Elgavish, and Dr. Hadar Benyamini (Bioinformatics Unit of the I-CORE Computation Center, Hebrew University and Hadassah Medical Center, Jerusalem, Israel) for their help with the bioinformatic analysis.
This work was supported by the Israel Science Foundation and Cabakoff grant foundation.
© International & American Associations for Dental Research 2020.
- bone regeneration
- bone remodeling
- gene expression
- histological healing
- tissue healing