# Identifying Approaches to Enhance Bone and Cartilage Regeneration

> **NIH VA I01** · BIRMINGHAM VA MEDICAL CENTER · 2021 · —

## Abstract

Failure to properly heal bone fractures is associated with significant morbidity and mortality. Additionally, the
need to properly form bone is vital to successful outcomes from surgeries ranging from joint replacement to
spinal fusion to dental implants. In an aging population, the biomedical need is even greater. The recent
identification of skeletal progenitor cells, composed of 8 subpopulations, capable of forming all three
components of the skeleton, bone, cartilage and stroma, promises to have a major impact on improving the
outcomes for these therapies. A key question that remains is what are the factors affecting eventual cell fate of
these skeletal progenitor cells. Our data on the matricellular protein DEL1 have shown it has an impact on
skeletal repair. We have preliminary data indicating that it has a direct effect on skeletal progenitor cell biology
and we propose that DEL1 plays an important role in their biology.
 Prior to this, our data had shown DEL1 had a biological effect on chondrocytes, but not on osteoblasts. We
demonstrated decreased numbers of mouse skeletal stem cells (mSSCs), and bone, cartilage, stroma
progenitors (BCSPs), the skeletal progenitor most important in fracture healing in the fracture callus, and we
propose the mechanism for decreased bone formation after fracture is due to an effect on skeletal progenitors
ability to expand after fracture. We plan on examining this first by isolating mSSCs and BCSPs, from knockout
(KO) and wild type (WT) mice and comparing their biology. We will examine the biology of BCSPs using in vitro
assays for cell proliferation, osteogenic and chondrogenic potential. BCSPs develop a different phenotype
termed the fracture BCSP (f-BCSP) that has greater proliferative ability and osteogenic potential after fracture,
and we will test whether the same change occurs in our KO mice. We will perform in vivo assays for
osteogenesis by implanting BCSPs into the renal capsule to examine how well they form bone.
 A key question in understanding how DEL1 affects formation of bone after fracture is to understand what
happens to skeletal progenitors after fracture in WT and KO mice. We will use lineage tracing techniques with
mice currently in our laboratory to examine the fate of daughter cells from individual clones of skeletal
progenitors cells.
 The final series of experiments represent our initial approaches to translating use of DEL1 into potential
therapies. First, we will perform a carefully controlled microarray experiment to identify pathways altered in KO
skeletal progenitors compared to WT. We will examine the ability of exogenous DEL1 to promote viability and
growth of skeletal stem cells grown in vitro. We will test the ability of DEL1 to stimulate bone and cartilage
formation of skeletal progenitor cells implanted into the renal capsule. Finally, we will examine whether
exogenous DEL1 protein placed at a fracture site can enhance normal fracture healing. We will also use a
separate ...

## Key facts

- **NIH application ID:** 10045950
- **Project number:** 5I01BX003754-05
- **Recipient organization:** BIRMINGHAM VA MEDICAL CENTER
- **Principal Investigator:** GEORGE P YANG
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2017-07-01 → 2022-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10045950

## Citation

> US National Institutes of Health, RePORTER application 10045950, Identifying Approaches to Enhance Bone and Cartilage Regeneration (5I01BX003754-05). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10045950. Licensed CC0.

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