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 10-14days after fracture. Single-cell RNA seq 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
- AD1212464
Entities
People
- Matthew Silva
- Steven Teitelbaum
Organizations
- Washington University in St. Louis