RESEARCH ARTICLE p16INK4a and its regulator l

by progressive cartilage erosion and lesions2Université de Montpellier-1, UFR de Medecine, F-34000, Montpellier, France Full list of author information is available at the end of the articleIntroduction Tissue loss of function and integrity are inherent to aging and age-related disease onset. Because senescent p16INK4a-positive cells accumulate within numerous tissues through-out life [1], recent strong evidence suggested that these cells contribute to tissue degeneration by sustaining chronic in-flammation and extracellular matrix remodeling [2]. In-deed, p16INK4a-positive cells exhibit a specific secretome called SASP (senescence-associated secretory phenotype) including pro-inflammatory cytokines (such as interleukin-6 (IL-6), IL-8, and IL-1β) and matrix remodeling regulatory metalloproteases (such as MMP1 and MMP13) [2]. Re-markably, specific conditional elimination of these cells in a premature aging murine model has revealed their essen-tial role in the onset of several age-related diseases [3]. Interestingly, Ink4a, which encodes an archetypical cyclin-dependent inhibitor (CKI) associated with senescence, is also known to participate in terminal differentiation onset of several cellular lineages [4,5]. Osteoarthritis (OA) is a chronic degenerative diseas