Friday, April 26, 2024 4/26/2024

The tendon cell is a robust alternative lineage for bone repair upon trauma or inflammation

Award Number: R01DE030643
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By Issue Date FY or Funding FY:

View Award Abstract

Regeneration of bone lost to injury or disease is a major health challenge. Most efforts toward bone regeneration center around the manipulation of exogenous cells from bone stem cell niches, which cannot provide sufficient cell numbers plus poor function, survival and integration of the injected cells with host tissues (cited from “RFA- DE-20-006”). In search for endogenous sources, we have studied potential roles of tendon as an alternative lineage for craniofacial bone growth and bone repairs (beyond its classic role: connecting muscles and bones for joint movement) as most bones of the skull below the calvaria are sheathed in the fibrous. Our unexpected and striking findings are a. The bone cell in bone ridges attached by tendon are Scx+ (a gene highly expressed in tendon); b. Tendon-formed bone (TFB) (similar to alveolar bone) is rich with a mixture of matrix components (such as tendon, cartilage and bone markers) that is distinct from conventional bone; c. TFB is built on the existing bone, and continuously expands, leading to more prominent bone ridges with aging; d. Tendon is not simply connected to bone but rather grows into and merges with the existing bone, making bone-tendon interface a mineralized continuum rather than a simple attachment; e. TFB varies depending on tensile forces with some transdifferentiating into chondrocytes while others directly entering into fibrogenesis and then osteogenesis, as well as on the location (such as zygomatic-temporal suture); and f. Tendon cells rapidly and robustly reprogram into bone-generating cells upon trauma or inflammation, leading to new long lasting large TFB. In response to this RFA (that requests an alternative lineage to promote endogenous healing and regeneration of craniofacial bones, and avoid injection of exogenous cells) we propose that the tendon cell, a natural but overlooked precursor for normal craniofacial bone growth, is a robust alternative lineage for bone regeneration in trauma or inflammation. We will achieve our objective by pursuing the following two highly related but independent specific aims: Aim 1: To define the plasticity of tendon cells in formation of craniofacial bone during development using mandible and temporal bones as testing models; Aim 2: To comprehensively study how an adult tendon cell, as an alternative lineage, switches its natural tendon program to an osteogenic program during trauma or inflammation. By virtue of our exciting discoveries, we are uniquely well positioned for this study. We have developed powerful and proven cell lineage tracing techniques with state of the art imaging and single cell RNA- seq methods to analyze cell plasticity in health and reprogramming in trauma. Upon completion of the proposed work, we expect to fill a glaring gap in our knowledge of craniofacial osteogenesis derived from tendon, and lay the foundation for establish tendon as an alternative lineage cell source for bone augmentation and bone regeneration in trauma and diseases.


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: 2023 ( Subtotal = -$121,902 )
2023	2022	TEXAS A & M UNIVERSITY SYSTEM HEALTH SCIENCE CENTER	6003 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Oral Diseases and Disorders Research	001	2	4/25/2023	NON-COMPETING CONTINUATION	-$1
2023	2021	TEXAS A & M UNIVERSITY SYSTEM HEALTH SCIENCE CENTER	6003 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Oral Diseases and Disorders Research	000	1	4/25/2023	NEW	-$121,901
														Subtotal = -$121,902

Issue Date FY: 2022 ( Subtotal = $1 )
2022	2022	TEXAS A&M UNIVERSITY SYSTEM, THE	8441 RIVERSIDE PARKWAY BLDG 1 STE 3100	BRYAN	TX	77807	BRAZOS	USA	Oral Diseases and Disorders Research	000	2	2/24/2022	NON-COMPETING CONTINUATION	$304,258
2022	2022	TEXAS A&M UNIVERSITY SYSTEM, THE	8441 RIVERSIDE PARKWAY BLDG 1 STE 3100	BRYAN	TX	77807	BRAZOS	USA	Oral Diseases and Disorders Research	002	2	5/13/2022	NON-COMPETING CONTINUATION	-$334,684
2022	2022	TEXAS A&M UNIVERSITY SYSTEM, THE	8441 RIVERSIDE PARKWAY BLDG 1 STE 3100	BRYAN	TX	77807	BRAZOS	USA	Oral Diseases and Disorders Research	001	2	4/21/2022	NON-COMPETING CONTINUATION	$30,427
														Subtotal = $1

Issue Date FY: 2021 ( Subtotal = $368,621 )
2021	2021	TEXAS A&M UNIVERSITY SYSTEM, THE	8441 RIVERSIDE PARKWAY BLDG 1 STE 3100	BRYAN	TX	77807	BRAZOS	USA	Oral Diseases and Disorders Research	000	1	2/8/2021	NEW	$368,621
														Subtotal = $368,621

Grand Total All Awards = $246,720

Top

All Categories

About

Search

Reports

Data Submission

Award Information

The tendon cell is a robust alternative lineage for bone repair upon trauma or inflammation

Award Number: R01DE030643

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer