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Microvascular integrity and its role in osteoarthritis

Award Number: R01AR087964
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: 09/01/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2031

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Microvascular integrity and its role in osteoarthritis - Osteoarthritis (OA) is a degenerative joint disease affecting more than 630 million adults worldwide and more than 32.5 million patients in the USA, and 12% of all OA is trauma induced OA. OA is characterized by cartilage destruction, local inflammation, joint stiffness and pain, leading to a loss of joint function. In addition to aging and obesity, the athletes, military service members, law enforcement personnel, and fire fighters are exposed to significant risk factors for OA. Currently, OA treatments are restricted to decreasing pain and inflammation, and at advanced stages joint replacement surgery. Articular cartilage is an avascular tissue; but highly vascularized synovial space providing nutrient and oxygen supply to chondrocytes. In OA, subchondral bone thickens, with blood vessel infiltrating at subchondral sites of articular cartilage, synovitis and angiogenesis occurring within the synovial membrane. It is not clear what occurs with the microvasculature within the synovial and subchondral bone in initial stages of OA, why articular cartilage gets vascularized and whether the microvascular damage post trauma leads to OA. Structural changes of articular cartilage with blood vessel infiltration and increased vascularity of subchondral bone are present in advanced OA. Damage to synovial blood vessels as a contributory cause of OA has not been explored. Our proposal aims to evaluate the role of the synovial and subchondral bone microvasculature in the development of OA. We hypothesize that loss of microvascular integrity within the joint is a triggering factor for OA. We propose to examine how damage to the vasculature within the joint affects articular cartilage and leads to OA. Our specific questions are: 1) Does mechanical stress induced injury affects knee microcirculation leading to articular cartilage damage; 2) Is it OA pathology initiated by damage to the joint microvasculature; 3) Will instability and increased permeability of blood vessel lead to accelerated OA development upon joint trauma, and 4) Can we by increasing endothelial cell tight junctions and decreasing blood vessel permeability prevent and/or delay OA? In the Aim 1 we will evaluate the role of blood vessel integrity within the synovial space in the development of osteoarthritis. We hypothesize that microvasculature damage in initial stage or the induction of synovial angiogenesis at later stage are underlying mechanisms for OA development. In the Aim 2, we will determine if increased blood vessel permeability leads to OA development in animals with previously intact knee joints; and evaluate if the instable and permeable blood vessels will increase progression of OA. In Aim 3 we will examine whether blood vessel stabilization by pharmacologic or genetic means can prevent OA development and/or alleviate OA progression. Evaluating direct role of vasculature and its integrity within knee joint we will determine whether vascular changes noticed within the OA joint are the consequence of an osteoarthritis or the cause. Evaluation of these mechanisms can lead to novel therapeutic approaches in osteoarthritis treatment.


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 = $421,367 )
2026	2026	UNIVERSITY OF ARKANSAS FOR MEDICAL SCIENCES	4301 W MARKHAM ST	LITTLE ROCK	AR	72205	PULASKI	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	8/28/2026	NEW	$421,367
														Subtotal = $421,367

Grand Total All Awards = $421,367

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Microvascular integrity and its role in osteoarthritis

Award Number: R01AR087964

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: 09/01/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2031

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