Age-Related Alterations in Signaling Pathways in Articular Chondrocytes: Implications for the Pathogenesis and Progression of Osteoarthritis - A Mini-Review.
Musculoskeletal conditions are a major burden on individuals, healthcare systems, and social care systems throughout the world, with indirect costs having a predominant economic impact. Aging is a major contributing factor to the development and progression of arthritic and musculoskeletal diseases. Indeed, aging and inflammation (often referred to as 'inflammaging') are critical risk factors for the development of osteoarthritis (OA), which is one of the most common forms of joint disease. The term 'chondrosenescence' has recently been introduced to define the age-dependent deterioration of chondrocyte function and how it undermines cartilage function in OA. An important component of chondrosenescence is the age-related deregulation of subcellular signaling pathways in chondrocytes. This mini-review discusses the role of age-related alterations in chondrocyte signaling pathways. We focus our attention on two major areas: age-dependent alterations in transforming growth factor-β signaling and changes in protein kinase and phosphoprotein phosphatase activities in aging chondrocytes. A better understanding of the basic signaling mechanisms underlying aging in chondrocytes is likely to facilitate the development of new therapeutic and preventive strategies for OA and a range of other age-related osteoarticular disorders.
Department of Rheumatology, Experimental Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands.
Peter
P
van der Kraan
Csaba
C
Matta
Ali
A
Mobasheri
D000368:Aged; D000375:Aging / Q000378:metabolism*; D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism*; D016922:Cellular Senescence / Q000502:physiology; D019902:Chondrocytes / Q000378:metabolism; D018450:Disease Progression; D006801:Humans; D010003:Osteoarthritis / Q000209:etiology* / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism
D016212:Transforming Growth Factor beta; D011494:Protein Kinases; D010749:Phosphoprotein Phosphatases