Studies of Joint Aging and Osteoarthritis

$2,119,925P01FY2010AGNIH

Scripps Research Institute, The, La Jolla CA

Investigators

Linked publications & trials

Paper 34991339 Paper 33744432 Paper 33115953 Paper 32572077 Paper 32339698 Paper 32158932 Paper 31493556 Paper 31028882 Paper 30950316 Paper 30373381 Paper 30111653 Paper 30081074 Paper 30059184 Paper 30031925 Paper 29963746 Paper 29929979 Paper 29914933 Paper 29908335 Paper 29758352 Paper 29678719 Paper 29628132 Paper 29609209 Paper 29457374 Paper 29444976 Paper 29411909 Paper 29301852 Paper 29065924 Paper 29035932 Paper 28957547 Paper 28934880 Paper 28916968 Paper 28801209 Paper 28682003 Paper 28657755 Paper 28621492 Paper 28463545 Paper 28430387 Paper 28334504 Paper 28220902 Paper 27925477 Paper 27884645 Paper 27780308 Paper 27769098 Paper 27729233 Paper 27693501 Paper 27624289 Paper 27582029 Paper 27527664 Paper 27391172 Paper 27370800 Paper 27118398 Paper 26881698 Paper 26842062 Paper 26805019 Paper 26792492 Paper 26773408 Paper 26738900 Paper 26585241 Paper 26527298 Paper 26458773 Paper 25995222 Paper 25940958 Paper 25940564 Paper 25937287 Paper 25914362 Paper 25893917 Paper 25716980 Paper 25708836 Paper 25691232 Paper 25640671 Paper 25605458 Paper 25565047 Paper 25554747 Paper 25530978 Paper 25362043 Paper 25312837 Paper 25266449 Paper 25221786 Paper 25188528 Paper 25186470 Paper 25092378 Paper 25047750 Paper 25035174 Paper 24972006 Paper 24857486 Paper 24594442 Paper 24591481 Paper 24554604 Paper 24530784 Paper 24489999 Paper 24269635 Paper 24225636 Paper 24199634 Paper 24166359 Paper 24028447 Paper 23962090 Paper 23940002 Paper 23883619 Paper 23706035 Paper 23686683

Abstract

DESCRIPTION (provided by applicant): This competing renewal continues to utilize human knee joints from donors across the adult age spectrum to establish phenotypic changes in articular cartilage and chondrocytes that are characteristic of normal joint aging and may predispose to the development of osteoarthritis (OA). The overall goal of this program is to begin with phenotype identification, proceed to elucidation of mechanisms and key cellular and molecular abnormalities in order to provide new directions for correcting aging-associated risk factors for OA and therapeutic interventions for established OA. Access to human tissues provides a unique opportunity to test the human and clinical relevance of novel basic and molecular mechanisms not only through correlative studies but also through an array of comprehensive in vitro studies with cells isolated from human tissues. The overall hypothesis proposes that cartilage aging is associated with loss and dysfunction that differentially affects cartilage cell subpopulations. Chondrocytes are compromised in function by aging-associated changes in signaling mechanisms and the inflammatory milieu of OA. The proposed program will continue the existing cores (A: Administration;B and C now combined into Core B: Tissue Acquisition, Morphology, and Cell Culture). The following 3 projects are proposed: Project 1, "Chondrocyte subpopulations in aging and osteoarthritis" (PI: M. Lotz) will characterize chondrocyte subpopulations and the role of Sox9-dependent activation of chondrocytes in normal and aging cartilage. Project 2, "Dysfunctional chondrocyte differentiation in aging cartilage" (PI: R. Terkeltaub) addresses the regulation of articular chondrocyte hypertrophy by altered Pi and PPi metabolism with focus on specific enzymes (NPP1, TNAP) and transporters (Ank, Pit-1). Project 4, "Mechanobiology of human articular cartilage degeneration: aging and osteoarthritis" (PI: R. Sah) will analyze biomechanical mechanisms of early and advanced cartilage degeneration and determine consequences for chondrocyte function and survival. Collectively, the results from the proposed studies will add important new information on chondrocyte biology, cartilage aging, and osteoarthritis pathophysiology.

View original record on NIH RePORTER →