# Trap+ Mononuclear Cells in Periosteal Bone Formation

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $360,250

## Abstract

Project Summary/ Abstract
Periosteal bone growth and modeling take place in the periosteum at the outer surface of cortical bones.
The perioseum, which covers the entire bone surface except the portion of bones that contains articular
cartilage, is one of the most osteogenic tissues in the body and plays a critical role in cortical expansion
during growth. Periosteal bone formation has different mechanisms from other areas of bone surface such
as endosteum, secondary spongiosa and trabecular bone remodeling, etc. Despite its physiological
significance, the periosteum is often overlooked when it comes to processes that occur in the underlying
cortical bone. Periosteal biology remains little investigated and poorly understood. Structurally, the
periosteum is composed of two layers; adjacent to the periosteal bone surface is a layer of loosely packed
cells essential for growth and repair of the underlying bone. Further outward is a layer of densely packed
periosteum derived stem cells (PDSCs) interspersed with lymphatics, blood vessels and nerve endings. The
microenvironment of the outer layer serves as a niche to maintain the PDSCs whilst the inner layer provides
an osteogenic microenvironment for periosteal bone formation. We have shown that there are no osteal
macrophages and Trap+ mononuclear cells in CSF-1 op/op mice (CSF-1-/-), and interestingly, no obvious
cortical bone formation. A single injection of rhM-CSF is sufficient for rescue of osteoclast recruitment and
survival in CSF-1-/- mice. These results suggest that periosteal macrophages are essential in maintenance
of periosteum microenvironment for periosteal bone formation. Moreover, we have shown that Trap+
mononuclear cells derived from wild WT mice secrete PDGF-BB to induce migration of mesenchymal
stromal/stem cells. Knockout of PDGF-BB in the Trap+ cell lineage reduces periosteal angiogenesis and
bone formation but PDSCs and matrix proteins are still present in the periosteum, suggesting periosteal
macrophages play more important role in maintenance of periosteum homeostasis. In addition, we have
found mechanical stress induces periosteal TRAP+ mononuclear cells to secrete PDGF-BB for angiogenesis
and bone formation in our preliminary data. Thus, we hypothesize that periosteal macrophages maintain
homeostasis of the periosteum and TRAP+ mononuclear cells recruit PDSCs from outward layer to
the periosteal surface for angiogenesis and bone formation. In this proposal, we will first determine the
role of periosteal macrophages in periosteum homeostasis. We will then determine the function of Trap+
mononuclear cells, specifically, the mechanisms by which PDSCs are recruited by Trap+ mononuclear cells
for periosteal bone formation. Finally, we will validate the role of TRAP+ mononuclear cells in mechanical
stress-induced periosteal bone formation.

## Key facts

- **NIH application ID:** 9902330
- **Project number:** 5R01AR071432-04
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Xu Cao
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $360,250
- **Award type:** 5
- **Project period:** 2017-04-14 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9902330

## Citation

> US National Institutes of Health, RePORTER application 9902330, Trap+ Mononuclear Cells in Periosteal Bone Formation (5R01AR071432-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9902330. Licensed CC0.

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