Involvement of bone morphogenic protein 2 in osteogenesis and angiogenesis during distraction osteogenesis
Embargo Date
2026-02-26
OA Version
Citation
Abstract
Bone is one of the only tissues in the body capable of full regeneration after a post-traumatic fracture. For bone repair to occur, osteogenesis must be coupled to angiogenesis to properly nourish the injured area. Bone morphogenetic protein 2 (BMP2) is a growth factor required for the initiation of bone repair and is synthesized by the vessels. Studying BMP2 may help to better understand how the process of bone repair and vessel proliferation are coupled. In distraction osteogenesis, a surgical ostomy is made and the separation of the bone fragments is mechanically made by the incremental separation of the two bone fragments. The mechanical stimulation primarily drives bone regeneration to use an intramembranous ossification process of direct bone formation without a cartilage intermediary. To study the role of BMP2 in coupling osteogenesis and angiogenesis, transgenic mice were used to express Cre recombinase that was driven from a tamoxifen-inducible smooth muscle actin (SMA) promoter. These mice were crossed with those containing BMP2 floxed genes allowing for the conditional deletion of the BMP2 gene in SMA-expressing cells. The deletion was started six days post-surgery at the beginning of the distraction process and continued throughout the remainder of the regenerative period. Tissue samples within the distraction gap were examined histologically on post-operative days 17 and 31, end of active distraction and end of the consolidation period, respectively. Histological data indicated that the deletion of BMP2 in vascular tissue resulted in a reduction of angiogenesis and subsequent reduction in bone development. H & E stains discovered that knocking out BMP2 will result in a slight decrease in bone development by day 31. Safranin-O with a fast green stain revealed the control group at day 17 had more cartilage formation within the gap compared to the BMP2 knockout. On day 31, the control samples appeared to have cartilage in the center of the distraction gap while the animals where BMP2 was knocked out had cartilage tissue more diffuse throughout the gap. Both respective experimental groups showed a larger number of osteoclasts within the distraction gap at the beginning of the consolidation phase at the end, showing an early remodeling of bone. This study helps to provide a basis for how BMP2 is useful for fracture repair by increasing both osteogenesis and angiogenesis post-fracture in the post-embryotic state.