Local clearance of senescent cells attenuates the development of post-traumatic osteoarthritis and creates a pro-regenerative environment

Nature Medicine 23, 775 (2017). doi:10.1038/nm.4324 Authors: Ok Hee Jeon, Chaekyu Kim, Remi-Martin Laberge, Marco Demaria, Sona Rathod, Alain P Vasserot, Jae Wook Chung, Do Hun Kim, Yan Poon, Nathaniel David, Darren J Baker, Jan M van Deursen, Judith Campisi & Jennifer H Elisseeff Senescent cells (SnCs) accumulate in many vertebrate tissues with age and contribute to age-related pathologies, presumably through their secretion of factors contributing to the senescence-associated secretory phenotype (SASP). Removal of SnCs delays several pathologies and increases healthy lifespan. Aging and trauma are risk factors for the development of osteoarthritis (OA), a chronic disease characterized by degeneration of articular cartilage leading to pain and physical disability. Senescent chondrocytes are found in cartilage tissue isolated from patients undergoing joint replacement surgery, yet their role in disease pathogenesis is unknown. To test the idea that SnCs might play a causative role in OA, we used the p16-3MR transgenic mouse, which harbors a p16INK4a (Cdkn2a) promoter driving the expression of a fusion protein containing synthetic Renilla luciferase and monomeric red fluorescent protein domains, as well as a truncated form of herpes simplex virus 1 thymidine kinase (HSV-TK). This mouse strain allowed us to selectively follow and remove SnCs after anterior cruciate ligament transection (ACLT). We found that SnCs accumulated in the articular cartilage and synovium af...
Source: Nature Medicine - Category: General Medicine Authors: Tags: Letter Source Type: research