title: An overview of underlying causes and animal models for the study of age-related degenerative disorders of the spine and synovial joints.
abstract: As human lifespan increases so does the incidence of age-associated degenerative joint diseases, resulting in significant negative socioeconomic consequences. Osteoarthritis (OA) and intervertebral disc degeneration (IDD) are the most common underlying causes of joint-related chronic disability and debilitating pain in the elderly. Current treatment methods are generally not effective and involve either symptomatic relief with non-steroidal anti-inflammatory drugs and physical therapy or surgery when conservative treatments fail. The limitation in treatment options is due to our incomplete knowledge of the molecular mechanism of degeneration of articular cartilage and disc tissue. Basic understanding of the age-related changes in joint tissue is thus needed to combat the adverse effects of aging on joint health. Aging is caused at least in part by time-dependent accumulation of damaged organelles and macromolecules, leading to cell death and senescence and the eventual loss of multipotent stem cells and tissue regenerative capacity. Studies over the past decades have uncovered a number of important molecular and cellular changes in joint tissues with age. However, the precise causes of damage, cellular targets of damage, and cellular responses to damage remain poorly understood. The objectives of this review are to provide an overview of the current knowledge about the sources of endogenous and exogenous damaging agents and how they contribute to age-dependent degenerative joint disease, and highlight animal models of accelerated aging that could potentially be useful for identifying causes of and therapies for degenerative joint diseases.
authors.affiliation: Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, 200 Lothrop Street, E1641 Biomedical Science Tower, Pittsburgh, Pennsylvania 15261, USA. von@upmc.edu
authors.forename: Nam
authors.initials: N
authors.lastname: Vo
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Niedernhofer
authors.forename: Luigi Aurelio
authors.initials: LA
authors.lastname: Nasto
authors.forename: Lloydine
authors.initials: L
authors.lastname: Jacobs
authors.forename: Paul D
authors.initials: PD
authors.lastname: Robbins
authors.forename: James
authors.initials: J
authors.lastname: Kang
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Evans
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D002358:Cartilage, Articular / Q000502:physiology; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000235:genetics; D004195:Disease Models, Animal; D004720:Endonucleases / Q000235:genetics; D006801:Humans; D007403:Intervertebral Disc / Q000502:physiology; D007592:Joint Diseases / Q000209:etiology*; D018384:Oxidative Stress; D013122:Spinal Diseases / Q000209:etiology*
chemical_list: D004268:DNA-Binding Proteins; D004720:Endonucleases; C499360:Ercc1 protein, mouse