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

Adrenergic receptors in osteoarthritis

Award Number: R21AR085845
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: 06/01/2026
PERIOD OF PERFORMANCE END DATE: 05/31/2028

Group Awards By:

View Award Description

Adrenergic receptors in osteoarthritis - Abstract Osteoarthritis (OA) is a debilitating disease of the joints involving progressive cartilage degeneration, with no disease modifying therapy available. therefore, it is important to identify novel molecular pathways that can be targeted for OA drug therapy. Sympathetic innervation and receptors characterize OA joint tissues. Although the importance of sympathetic signaling through AR is characterized in skeletal homeostasis, its cartilage-specific role in OA development and progression is largely unknown. Adrenergic receptors are G protein-coupled receptors, their signaling is regulated by the kinase GRK2. We recently demonstrated a key role for GRK2 in diminishing the homeostatic G-protein signal through receptor desensitization in chondrocytes leading to their pathologic differentiation, cartilage degeneration and OA progression. Importantly, we showed that inhibiting GRK2, by genetic deletion or by inhibitory drugs, reverses this process and recovers the homeostatic G-protein signal. However, specific receptors that are desensitized by GRK2 during OA pathogenesis are unknown. Our preliminary data showed decreased b2-AR expression and signaling in OA human and mouse cartilage, with opposite effects of b2-AR stimulation in early and late OA. Altogether, this supports our overarching hypothesis that b2-AR signaling is altered in OA cartilage through GRK2-mediated desensitization, and that correcting this alteration can be a novel therapeutic strategy for OA. To validate our hypothesis, in the first aim we use genetic and pharmacologic manipulations of AR in chondrocytes of DMM mice at early and late phases of OA to determine its role in OA development and progression. In the second aim, we use similar manipulations to determine the role of GRK2- mediated b2-AR desensitization in OA development and progression in OA mice and study the role of b2-AR resensitization in human normal and OA cartilage. These studies will fill a gap in the literature by defining b2-AR regulatory and signaling changes in the joint cartilage during OA, it will enable us to discover a novel therapeutic strategy and targets for OA.


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 = $366,053 )
2026	2026	PENNSYLVANIA STATE UNIVERSITY	500 UNIVERSITY DRIVE	HERSHEY	PA	17033	DAUPHIN	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	5/13/2026	NEW	$366,053
														Subtotal = $366,053

Grand Total All Awards = $366,053

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Adrenergic receptors in osteoarthritis

Award Number: R21AR085845

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: 06/01/2026

PERIOD OF PERFORMANCE END DATE: 05/31/2028

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer