Accelerated Healing of Traumatic Fractures and Nonunion
Abstract
Our goals are to determine the mechanisms for rapid bone formation observed in DT/DTRADQ mice wherein adiponectin expressing cells are ablated, and to harness this knowledge to test new strategies for promoting osteogenesis to treat fracture nonunion. Contrary to our initial hypothesis, we find that osteoblasts stimulated by DT/DTRADQ are not derived from adiponectin-lineage cells. Rather, adiponectin expressing CAR cells in the bone marrow express BMP receptor inhibitors, and ablation of these cells in DT/DTRADQ promotes BMP signaling and osteogenesis by activating Col1a1-3.6 kB expressing osteoprogenitors lining the marrow cavity, which then differentiate into non-proliferative, mature Col1a1-2.3 kB osteoblasts. We are testing whether delivery of these primed DT/DTRADQ bone cells via a polymer scaffold accelerates segmental defect non-union healing in WT mice. Relevant to the identification of 3.6Col1a1 cells as essential to DT/DTRADQ intramedullary osteogenesis, we find that the proliferation of these cells is also essential to periosteal callus formation after fracture. Single-cell RNAseq analysis of periosteal callus from healing and non-healing bones has been completed, and examination of the3.6Col1a1 expressing cells is ongoing with the goal of determining which subpopulation of osteoprogenitors is responsible for callus formation. Finally, we have completed a study showing that driving BMP2 expression in cells delivered in a polymer scaffold can enhance osteogenesis in non-healing fractures.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2022
- Accession Number
- AD1190504
Entities
People
- Matthew Silva
- Steven Teitelbaum
Organizations
- Washington University in St. Louis