Chondrosenescence: Definition, hallmarks and potential role in the pathogenesis of osteoarthritis

Abstract

Aging and inflammation are major contributing factors to the development and progression of arthritic and musculoskeletal diseases. "Inflammaging" refers to low-grade inflammation that occurs during physiological aging. In this paper we review the published literature on cartilage aging and propose the term "chondrosenescence" to define the age-dependent deterioration of chondrocyte function and how it undermines cartilage function in osteoarthritis. We propose the concept that a small number of senescent chondrocytes may be able to take advantage of the inflammatory tissue microenvironment and the inflammaging and immunosenescence that is concurrently occurring in the arthritic joint, further contributing to the age-related degradation of articular cartilage, subchondral bone, synovium and other tissues. In this new framework "chondrosenescence" is intimately linked with inflammaging and the disturbed interplay between autophagy and inflammasomes, thus contributing to the age-related increase in the prevalence of osteoarthritis and a decrease in the efficacy of articular cartilage repair. A better understanding of the basic mechanisms underlying chondrosenescence and its modification by drugs, weight loss, improved nutrition and physical exercise could lead to the development of new therapeutic and preventive strategies for osteoarthritis and a range of other age-related inflammatory joint diseases. Aging is inevitable but age-related diseases may be modifiable.

Chondrocyte secretome: a source of novel insights and exploratory biomarkers of osteoarthritis

“…Pro-inflammatory cytokines, prostaglandins and reactive oxygen species (ROS) activate the normally quiescent articular chondrocytes and induce them to undergo a phenotypic shift through a phenomenon recently described as "chondrosenescence", leading to further disruption of homeostasis and metabolism in cartilage [7]. Effectively, chondrosenescence is the term that describes the agedependent deterioration of chondrocyte function and how it undermines cartilage function in OA.…”

“…In the upper zone, cellular proliferation and hypertrophy are observed, whereas the mid and deep zones display increased expression of type II collagen [6]. As OA progresses, cartilage is lost and chondrocytes undergo senescence, due to a combination of replicative exhaustion and oxidative stress [7].…”

An update on the pathophysiology of osteoarthritis

“…We propose that a small number of "senescent chondrocytes" may be able to take advantage of the inflammatory tissue microenvironment and the inflammaging and immunosenescence that is concurrently occurring in the arthritic joint, further contributing to the age-related degradation of articular cartilage, subchondral bone, synovium and other tissues (13). In this framework "chondrosenescence" is intimately linked with obesity, lifestyle choices and inflammaging and at the molecular level with the disturbed interplay between autophagy and inflammasomes, thus contributing to the age-related increase in the prevalence of OA and a decrease in the efficacy of articular cartilage repair (47).…”

“…Cohort studies have demonstrated that after age, obesity and metabolic disease are major risk factors for the development of OA (4,5). OA is now generally accepted to be an inflammatory and biomechanical whole-organ disease that is influenced by a number of factors including joint shape and dysplasia (6), obesity (7), synovitis (8-10), complement proteins (11), systemic inflammatory mediators (1,12), inflammaging (13,14), innate immunity (15), the low-grade inflammation (16) induced by metabolic syndrome (1,17) and diabetes mellitus (18). However, despite the fact that all joint tissues are potentially implicated in disease initiation and progression in OA, it is the articular cartilage component that has received the most attention in the context of aging, injury and disease (2).…”

Sarcopenia and Exercise “The State of the Art”

“…These physiological events are also due to the reduced muscle regeneration ability. Indeed, the unbalanced turnover of muscle protein and tissue remodeling are associated with impaired muscle cell recruitment and cell death [1,2]. Muscle aging is a multifactorial irreversible process associated with significant decline in muscle mass and functions [3].…”