Personal non-commercial use only

ABSTRACT. Objective. The morphology of articular cartilage (AC) enables painless movement. Aging and mechanical loading are believed to influence development of osteoarthritis (OA), yet the connection remains unclear. Methods. This narrative review describes the current knowledge regarding this area, with the literature search made on PubMed using appropriate keywords regarding AC, age, and mechanical loading. Results. Following skeletal maturation, chondrocyte numbers decline while increasing senescence occurs. Lower cartilage turnover causes diminished maintenance capacity, which produces accumulation of fibrillar crosslinks by advanced glycation end products, resulting in increased stiffness and thereby destruction susceptibility. Articular cartilage (AC) covers bone surfaces and allows for almost friction-free movement. Unfortunately, AC is susceptible to acute injury and degenerative conditions, e.g., osteoarthritis (OA), and because cartilage has very poor healing potential, OA is a considerable medical challenge. OA is no longer solely seen as 1 single disease, instead 5 OA phenotypes have been suggested, i.e., genetic, metabolic, pain, age, and structural/post-traumatic 1 . Our narrative review is meant as a covering overview of the main OA phenotypes (related to aging and mechanical loading), and is aimed to include studies of molecular, biochemical, physiological, and clinical designs. To clarify these OA phenotypes, basic information about AC morphology and key components is provided. This is followed by a review of the effect of age and mechanical influence on the morphology, along with the underlying cell signaling, because, as demonstrated, OA is not merely a mechanical/physical "wear and tear" disease. The literature search was performed on PubMed using appropriate keywords regarding exercise/mechanical load, articular cartilage, metabolism/turnover, OA, extracellular matrix, and cell signaling/transduction. Morphology AC consists of the chondrocyte surrounded by an extracellular matrix (ECM), subdivided into areas in a pericellular matrix (PCM) immediately adjacent to the cell, a territorial matrix farther away, and an interterritorial matrix 2 . ECM contains a fibrillar network of both collagens and noncollagenous matrix components embedded in a viscous gel-like ground/basic substance. The fibers are oriented differently and divide the uncalcified AC into 3 zones: superficial zone (SZ) with parallel fiber orientation, intermediate zone (IZ) with random, and finally deep zone (DZ) with vertical orientation. A tidemark represents the DZ transition into the mineralized/calcified fourth zone followed by the subchondral bone below 3 . The ground/basic substance contains the extra

:4; Personal non-commercial use only

ABSTRACT. Objective. The morphology of articular cartilage (AC) enables painless movement. Aging and mechanical loading are believed to influence development of osteoarthritis (OA), yet the connection remains unclear. Methods. This narrative review describes the current knowledge regarding this area, with the literature search made on PubMed using appropriate keywords regarding AC, age, and mechanical loading. Results. Following skeletal maturation, chondrocyte numbers decline while increasing senescence occurs. Lower cartilage turnover causes diminished maintenance capacity, which produces accumulation of fibrillar crosslinks by advanced glycation end products, resulting in increased stiffness and thereby destruction susceptibility. Articular cartilage (AC) covers bone surfaces and allows for almost friction-free movement. Unfortunately, AC is susceptible to acute injury and degenerative conditions, e.g., osteoarthritis (OA), and because cartilage has very poor healing potential, OA is a considerable medical challenge. OA is no longer solely seen as 1 single disease, instead 5 OA phenotypes have been suggested, i.e., genetic, metabolic, pain, age, and structural/post-traumatic 1 . Our narrative review is meant as a covering overview of the main OA phenotypes (related to aging and mechanical loading), and is aimed to include studies of molecular, biochemical, physiological, and clinical designs. To clarify these OA phenotypes, basic information about AC morphology and key components is provided. This is followed by a review of the effect of age and mechanical influence on the morphology, along with the underlying cell signaling, because, as demonstrated, OA is not merely a mechanical/physical "wear and tear" disease. The literature search was performed on PubMed using appropriate keywords regarding exercise/mechanical load, articular cartilage, metabolism/turnover, OA, extracellular matrix, and cell signaling/transduction. Morphology AC consists of the chondrocyte surrounded by an extracellular matrix (ECM), subdivided into areas in a pericellular matrix (PCM) immediately adjacent to the cell, a territorial matrix farther away, and an interterritorial matrix 2 . ECM contains a fibrillar network of both collagens and noncollagenous matrix components embedded in a viscous gel-like ground/basic substance. The fibers are oriented differently and divide the uncalcified AC into 3 zones: superficial zone (SZ) with parallel fiber orientation, intermediate zone (IZ) with random, and finally deep zone (DZ) with vertical orientation. A tidemark represents the DZ transition into the mineralized/calcified fourth zone followed by the subchondral bone below 3 . The ground/basic substance contains the extra