# Roles of SOXC proteins in osteogenic cells

> **NIH NIH R01** · CHILDREN'S HOSP OF PHILADELPHIA · 2020 · $494,509

## Abstract

PROJECT SUMMARY
Congenital and acquired bone diseases constitute a major public health issue. Research conducted in the last
decades has led to improved preventive and therapeutic interventions, but the diseases continue today to
cause disability, morbidity and mortality at a high rate. More research is therefore needed to further decipher
disease mechanisms and develop better interventions. This project is designed to contribute to this effort by
increasing current knowledge of the molecular regulation of skeletal stem cells (SSCs) and their osteoblastic
descendants. We will test the hypothesis that SOXC transcription factors critically control bone formation from
development onwards by directing SSCs and pre-osteoblasts to express a wide array of genes that ensure
their self-renewal and inhibit their osteoblastic differentiation. This hypothesis is supported by preliminary
evidence that the SOXC genes, i.e., Sox4, Sox11, and Sox12, are actively expressed in SSCs and early
osteoblastic cells in the mouse, and that both their specific co-inactivation and the overexpression of SOX11 in
SSCs result in underdeveloped bone in embryos and in low bone mass in adult mice. This hypothesis is also
supported by published evidence that SOX4 is a candidate gene for osteoporosis and low bone mass in
humans and that SOX11 heterozygous mutations cause characteristic dysmorphic features. Two specific aims
are proposed to test this hypothesis. Aim 1 is to use SOXC loss-of-function and gain-of-function mouse models
to definitively assess the importance of SOXC genes in osteogenesis throughout life. Aim 2 is to use cutting-
edge molecular and functional approaches to identify the transcriptional targets of SOXC proteins in SSCs and
pre-osteoblasts, and the importance of these targets in mediating the roles of SOXC proteins in these cells.
Altogether, it is expected that new knowledge acquired upon completion of this project will significantly deepen
current understanding of SSC and skeleton regulation from development to late adulthood and will thereby
spark novel ideas and provide new means to better understand and treat bone diseases.

## Key facts

- **NIH application ID:** 9949649
- **Project number:** 5R01AR068308-05
- **Recipient organization:** CHILDREN'S HOSP OF PHILADELPHIA
- **Principal Investigator:** VERONIQUE M LEFEBVRE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $494,509
- **Award type:** 5
- **Project period:** 2018-07-05 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9949649

## Citation

> US National Institutes of Health, RePORTER application 9949649, Roles of SOXC proteins in osteogenic cells (5R01AR068308-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9949649. Licensed CC0.

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