# Role of GI OSTERIX in Gut and Bone Biology

> **NIH NIH R21** · RHODE ISLAND HOSPITAL · 2021 · $394,064

## Abstract

PROJECT SUMMARY:
 It has been known for decades that the gut profoundly regulates bone mineral homeostasis by influencing
the development and function of bone-forming osteoblasts and bone-degrading osteoclasts. At the cellular
and molecular levels, how the gut affects the bone and whether skeletal and gastrointestinal (GI) epithelium
development is functionally synchronized remains largely unknown. The work outlined in this proposal builds
on our novel and exciting discovery that the zinc finger protein OSTERIX, which to this point has been
considered a bone-specific master transcription factor, is robustly expressed in the intestinal crypts. OSTERIX
expression has not yet been reported in extraskeletal tissues. We discovered OSTERIX in GI epithelium while
examining the role of the phosphatase SHP2 in mouse skeletal development using Osterix-Cre-mediated
deletion of PTPN11 foxed alleles. Subsequently, we confirmed that the OSTERIX promoter is active and
OSTERIX protein is expressed in the GI crypt base stem cells (CBCs). Given OSTERIX’s central role in bone
development, we hypothesize that OSTERIX in the GI crypt cells may participate in GI epithelial development
and bone mineral homeostasis. Building on these novel findings we will take the R21 funding mechanism and
determine how OSTERIX modulates the self-renewal and multiple lineage differentiation of the GI CBCs, and
examine whether and how OSTERIX in the GI epithelium modulates osteoblast and osteoclast function and
bone mineral homeostasis. In Specific Aim #1 we will test the hypothesis that OSX maintains CBC stemness
and regulates multilineage differentiation using genetically modified mice in combination of approaches
including marker colocalization, live cell-lineage tracing, organoid culture, histology, and
immunohistochemical staining. In Specific Aim #2 we will test the hypothesis that GI OSX regulates OB and
osteoclast function and bone mineral homeostasis by modulating the expression of GI epithelial growth factors
and hormones. Approaches including new bone formation assays, RNAScope®, histomorphometry,
immunostaining, and biochemical assays of bone metabolic markers will be applied in this study.

## Key facts

- **NIH application ID:** 10388883
- **Project number:** 1R21AR079195-01A1
- **Recipient organization:** RHODE ISLAND HOSPITAL
- **Principal Investigator:** Wentian Yang
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $394,064
- **Award type:** 1
- **Project period:** 2021-09-28 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10388883

## Citation

> US National Institutes of Health, RePORTER application 10388883, Role of GI OSTERIX in Gut and Bone Biology (1R21AR079195-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10388883. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*