Accelerated Healing of Traumatic Fractures and Nonunion
Abstract
Depletion of marrow CAR cells, which are early osteoblast progenitors increases bone mass, 10 fold likely by eliminating BMPR inhibitors. Confirming a central role for CAR cells, depleting LepR+ cells in LepR-Cre mice similarly decreases marrow BMPR inhibitors and markedly increases bone mass . Thus, CAR/LepR+ cells are not only osteoblast progenitors, but also the principal source of BMP inhibitors in marrow, negatively regulating bone formation. Using a polymer scaffold to improve toughness and cell infiltration we will assess CAR cell free bone cells as well as viral BMP2 on segmental defect nonunion healing in WT mice . Relevant to our prior identification of 3.6Col1a1 cells as essential for periosteal callus formation the critical window for proliferation of these cells is the first 10-14 days after fracture. Single-cell RNAseq of periosteal callus from 3.6Col1-TK mice shows that nonhealing bones have no deficit in MSCs but are depleted of osteoblasts as well as chondrocytes. Data using Rosa-TK mice shows that proliferation of both early and mature osteoblasts is essential for fracture callus formation, suggesting that the mature osteoblast is a post-mitotic cell in the setting of fracture healing.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2023
- Accession Number
- AD1212468
Entities
People
- Matthew Silva
- Steven Teitelbaum
Organizations
- University of Washington