Roles of articular cartilage aging and chondrocyte senescence in the pathogenesis of osteoarthritis

Abstract

Osteoarthritis (OA), the disease characterized by joint pain and loss of joint form and function due to articular cartilage degeneration, is not an inevitable consequence of aging, but a strong association exists between age and increasing evidence of OA. Aging changes in articular cartilage that increase the risk of articular cartilage degeneration include fibrillation of the articular surface, decrease in the size and aggregation of proteoglycan aggrecans, increased collagen cross-linking and loss of tensile strength and stiffness. These alterations are most likely primarily the result of aging changes in chondrocyte function that decrease the ability of the cells to maintain the tissue including decreased synthetic activity, synthesis of smaller less uniform aggrecans and less functional link proteins and decreased responsiveness to anabolic growth factors. Our recent work suggests that the cause of the age-related loss of chondrocyte function may be progressive senescence of articular cartilage chondrocytes marked by a decline in mitotic activity, increased expression of the senescence-associated enzyme beta-galactosidase and erosion of telomere length. New efforts to prevent the development or progression of OA might include strategies that delay the onset of chondrocyte senescence or replace senescent cells.

Figure 1. Incidence of Symptomatic Knee Osteoarthritis vs Age

Histogram showing that the incidence of knee osteoarthritis increases with age in men and women

Figure 2. Prevalence of Humeral and Patellar Articular Surface Fibrillation versus Age

Prevalence of humeral and patellar articular surface fibrillation determined at autopsy. (This histogram was developed from data originally published by Collins and Meachim [1961] and reported by Freeman in Freeman MAR: Adult Articular Cartilage. 2nd ed. 1979, Tunbridge Wells: Pitman Medical Publishing. pp. 560

Figure 3. Prevalence of Ankle and Knee Articular Surface Fibrillation and Degeneration versus Age

Prevalence of ankle and knee articular surface fibrillation determined at autopsy. (This histogram was developed from data reported by Koepp et al.21)

Figure 4

Electron micrographs of bovine articular cartilage proteoglycan aggregates

Figure 5

Histogram showing the decrease in human proteoglycan aggrecan length with age

Figure 6

Graph showing how the incidence of knee osteoarthritis and erosion of articular cartilage chondrocyte telomere length (a marker of cell senescence) increase with age,