Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Role of GI OSTERIX in Gut and Bone Biology

Award Number: R21AR079195
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/28/2021
PERIOD OF PERFORMANCE END DATE: 08/31/2025

Group Awards By:

View Award Description

Role of GI OSTERIX in Gut and Bone Biology - 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = -$4,354 )
2026	2021	RHODE ISLAND HOSPITAL	593 EDDY ST	PROVIDENCE	RI	02903	PROVIDENCE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	2/25/2026	NEW	-$4,354
														Subtotal = -$4,354

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2021	RHODE ISLAND HOSPITAL	593 EDDY ST	PROVIDENCE	RI	02903	PROVIDENCE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	1	8/20/2024	NEW	$0
2024	2021	RHODE ISLAND HOSPITAL	593 EDDY ST	PROVIDENCE	RI	02903	PROVIDENCE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	10/23/2023	NEW	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $394,064 )
2021	2021	RHODE ISLAND HOSPITAL	593 EDDY ST	PROVIDENCE	RI	02903	PROVIDENCE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	9/28/2021	NEW	$394,064
														Subtotal = $394,064

Grand Total All Awards = $389,710

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Role of GI OSTERIX in Gut and Bone Biology

Award Number: R21AR079195

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/28/2021

PERIOD OF PERFORMANCE END DATE: 08/31/2025

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer