Osteoarthritis in the context of ageing and evolution: Loss of chondrocyte differentiation block during ageing

doi:10.1016/j.arr.2007.10.001

Ageing Research Reviews

Volume 7, Issue 2, April 2008, Pages 106-113

https://doi.org/10.1016/j.arr.2007.10.001 Get rights and content

Abstract

Ageing is the main risk factor of primary osteoarthritis (OA) and OA is the disease most strongly correlated with ageing. Both in humans and other animals OA development appears to be not strictly time-dependent but to hold pace with ageing processes. A characteristic of OA is deviant behaviour of chondrocytes in articular cartilage. These chondrocytes resemble terminal differentiated chondrocytes in growth plates and actively produce matrix degrading enzymes. The latter results in cartilage degeneration and eventually OA. We postulate that at a young age progression of chondrocyte differentiation is actively blocked in articular cartilage. This block declines when the evolutionary pressure to maintain this block, after reproductive life, is minimized. The loss of this differentiation block, maybe as a result of changes in chondrocyte TGF beta signalling, results in combination with normal joint loading in cartilage degeneration and OA.

Introduction

The only way to prevent ageing is an early death. With regard to ageing one has to separate theoretical life span from the actual life expectancy. Human life expectancy has increased tremendously from 20 up to 80 years in the western world but maximal life span has remained stable. The maximal life span of Homo sapiens is about 100–120 years and this has not changed over the years as far as is known. Given that life expectancy for most individuals has been short, age-related diseases were rare in the older days and only nowadays this is an exponentially increasing problem.

Ageing is any time related process. However, just because two processes occur in parallel this not necessarily implies a cause and effect relationship. The process of ageing is time-related and osteoarthritis is also time-related. Ageing is the risk factor most strongly related to osteoarthritis. However, whether ageing processes are responsible for OA development is not elucidated yet.

Section snippets

Evolution of ageing and senescence

Ageing and senescence have been for most individuals in human evolution a bridge to far. The expectation of human life at birth in early human history was only 20 years and in ancient Greece and the Roman Empire this was only 30–35 years, but it was long enough to allow for children to be born and for the populations to expand (Waterlow, 1989). Also many animal species show a short life expectancy in nature. In the wild, over 90% of mice die within their first year of life (Phelan and Austad,

Ageing and osteoarthritis

OA incidence appears to hold pace with life expectancy. Not only humans develop OA but many other animals have been reported to develop OA. OA has been reported in terrestrial mammalian species, such as elephants, dogs, mice but also in water-bound species like whales. Birds develop OA irrespective of their size and posture and also in reptiles, such as turtles, OA has been observed (Rothschild and Panza, 2006, Kessler et al., 1986, Harcourt, 1971). Animals with a long life expectancy (humans)

Ageing and maintenance of articular cartilage

Cartilage can be divided in temporary and permanent cartilage. Temporary cartilage is replaced by bone while permanent cartilage is inhibited to take this route under normal conditions. The default route of chondrocyte differentiation appears to be terminal differentiation ending with endochondral ossification (Szuts et al., 1998, Pacifici et al., 1990). In vitro chondrogenic differentiation of mesenchymal stem cells and chondrocytes precursors results in terminal differentiation as

Concluding remarks

Osteoarthritis has been termed Alzheimer of articular cartilage (Aigner et al., 2004). Both OA and Alzheimer's disease (AD) are highly age-associated diseases occurring in tissues with little repair capacity. Interesting, a remarkable relationship between reduced TGF-beta signaling and AD has been demonstrated (Tesseur and Wyss-Coray, 2006, Luo et al., 2006, Tesseur et al., 2006, Wyss-Coray, 2006, Das and Golde, 2006). Alzheimer's disease, characterized by progressive neurodegeneration, showed

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ReviewOsteoarthritis in the context of ageing and evolution: Loss of chondrocyte differentiation block during ageing

Abstract

Introduction

Section snippets

Evolution of ageing and senescence

Ageing and osteoarthritis

Ageing and maintenance of articular cartilage

Concluding remarks

Osteoarthritis Cartilage

Exp. Gerontol.

Curr. Opin. Pharmacol.

Osteoarthritis Cartilage

Osteoarthritis Cartilage

Mech. Ageing Dev.

J. Biol. Chem.

Osteoarthritis Cartilage

Exp. Cell Res.

Mech. Ageing Dev.

Osteoarthritis Cartilage

Matrix Biol.

Am. J. Pathol.

Osteoarthritis Cartilage

Matrix Biol.

Osteoarthritis Cartilage

Gene expression and proliferation analysis in young, aged, and osteoarthritic sheep chondrocytes effect of growth factor treatment

J. Orthop. Res.

Apoptosis and cellular vitality: issues in osteoarthritic cartilage degeneration

Arthritis Rheum.

Roles of chondrocytes in the pathogenesis of osteoarthritis

Curr. Opin. Rheumatol.

Aging theories of primary osteoarthritis: from epidemiology to molecular biology

Rejuvenation Res.

Ageing and zonal variation in post-translational modification of collagen in normal human articular cartilage. The age-related increase in non-enzymatic glycation affects biomechanical properties of cartilage

Biochem. J.

Changes in the cartilage proteoglycans in relation to age and osteoarthrosis

Acta Biol. Hung.

Osteoarthritis chondrocytes die by apoptosis. A possible pathway for osteoarthritis pathology

Arthritis Rheum.

Reduced transforming growth factor-beta signaling in cartilage of old mice: role in impaired repair capacity

Arthritis Res. Ther.

Articular cartilage: degeneration and osteoarthritis, repair, regeneration, and transplantation

Instr. Course Lect.

Bone abnormalities in latent TGF-[beta] binding protein (Ltbp)-3-null mice indicate a role for Ltbp-3 in modulating TGF-[beta] bioavailability

J. Cell Biol.

Dysfunction of TGF-beta signaling in Alzheimer's disease

J. Clin. Invest.

Accumulation of advanced glycation end products as a molecular mechanism for aging as a risk factor in osteoarthritis

Arthritis Rheum.

Increased matrix metalloproteinase-13 production with aging by human articular chondrocytes in response to catabolic stimuli

J. Gerontol. A Biol. Sci. Med. Sci.

Signaling through the small G-protein Cdc42 is involved in insulin-like growth factor-I resistance in aging articular chondrocytes

J. Orthop. Res.

Growth factor responsiveness of human articular chondrocytes in aging and development

Arthritis Rheum.

The palaeopathology of animal skeletal remains

Vet. Rec.

Linkage of chondrocyte apoptosis and cartilage degradation in human osteoarthritis

Arthritis Rheum.

Critical roles for collagenase-3 (Mmp13) in development of growth plate cartilage and in endochondral ossification

Proc. Natl. Acad. Sci. U.S.A.

Mitochondrial oxidative phosphorylation is a downstream regulator of nitric oxide effects on chondrocyte matrix synthesis and mineralization

Arthritis Rheum.

Review
Osteoarthritis in the context of ageing and evolution: Loss of chondrocyte differentiation block during ageing