Review

article

Effects of aging and physical activity on articular cartilage:

a literature review

Novelli, C., Costa, JBV. and Souza, RR.*

Laboratory of Morphoquantitative Studies, São Judas Tadeu University – USJT,

Rua Taquari, 546, São Paulo, Brazil
*E-mail: [email protected]

Abstract
The overall aim of this literature review is, by making use of major databases, to introduce the concepts
about the articular cartilage structure and the effects of aging on articular cartilage. The effects of physical
exercises on those cartilages are also discussed. The most important observations found are: cartilage thickness
decreases gradually with age as well the content of proteoglycans and water, and there is an increase and the
collagen fibrils, which may be associated with the increased rigidity and fragility of the articular cartilage. When
properly done, physical activities produce compressive stimuli which enhance the activity of chondrocytes
increasing its nuclear volume density per area, as well as the width of the layers leading to greater resistance to
compression. Another consequence is extracellular matrix hydration resulting in greater mechanical resistance
and elasticity and a consequent increase the number of collagen fibrils which generates greater resistance to
deformation and implies less rigidity. These facts reduce the risk of breakdown of cartilage when it is subjected
to high mechanical demand.
Keywords: articular cartilage, exercise.

1 Introduction
Articular cartilage is a connective tissue that covers the and MUIR, 1988; GOMES, 2001). The interaction between
articulating surfaces of bones within synovial joints. Its aggrecan and hyaluronic acid is responsible for retaining
primary function is to absorb the mechanical shock and water in the cartilage (CARNEY and MUIR, 1988). The
distribute the weight having a minimum coefficient of interaction between collagen fibrils and aggrecan makes
friction (LEVANON and STEIN, 1991; HARDINGHAM, the extracellular matrix of cartilage highly hydrophilic,
FOSANG and DUDHIA, 1992; HEISE and TOLEDO, which leads to high resistance to compressive mechanical
1993; TRATTNIG, 1997; ALBERTS, BRAY, LEWIS et al., loads in addition to regulating the movement of molecules
1999; HUBER, TRATTNIG and LINTNER, 2000). in the extracellular medium (MAROUDAS, 1976;
Articular cartilage is composed of two different elements: PALMOSKI, COLYER and BRANDT, 1981; MUIR, 1983,
cells called chondrocytes and an extracellular matrix O’CONNOR, ORFORD, and GARDNER, 1988; WIGHT,
(BURSTEIN, BASHIR and GRAY, 2000). HEINEGARD and HASCALL, 1991; HARDINGHAM,
Chondrocytes regulate the metabolism of extracellular MUIR, KWAN  et  al., 1987; SÄÄMÄMEN, KIVIRANTA,
matrix through mechanical, physicochemical, and JURVELIN et al., 1994; ALBERTS, BRAY, LEWIS et al.,
electrical stimuli (TRATTNIG, 1997; POOLE, KOJIMA, 1999; CULAV, CLARK and MERRILEES, 1999; HUBER,
YASUDA  et  al., 2001) whose intensity modulates cellular TRATTNIG and LINTNER, 2000).
responses (SMITH, LIN, TRINDADE et al., 2000). Collagen, together with the PGs, is also responsible
The extracellular matrix is composed of a network of for resisting the deformations to which the cartilage is
collagen fibrils, water, and large amounts of proteoglycans subjected (ROUGHLEY and WHITE, 1980; SCHMIDT,
(HARDINGHAM, FOSANG and DUDHIA, 1992, MOW, CHUN  et  al., 1990). During the aging process,
VOGEL, 1994; TRATTNIG, 1997; HUBER, TRATTNIG there are changes in the structure of the extracellular matrix
and LINTNER, 2000). Proteoglycans (PGs) are (ROUGHLEY, 2001) resulting in a tissue with reduced
molecules that are made up of a core protein attached ability to absorb mechanical stress (LOESER, 2000;
to glycosaminoglycan (GAG) chains (HASCALL and HULDELMAIER, GLASER, ENGLMEIER  et  al., 2001)
HASCALL, 1981; HASCALL and KIMURA, 1982; and more susceptible to degenerative diseases.
VAN  KUPPEVELT, DOMEN, CREMERS  et  al., Osteoarthritis is a degenerative joint disease, which is
1984; WIGHT, HEINEGARD and HASCALL, 1991; associated with aging and mainly affects the articular cartilage.
RUOSLAHTI and YAMAGUCHI, 1991; YANAGISHITA, It is one of the most common causes of pain, disability,
1993; BRANDAN, 1994, NISHIMURA, HATTORI, and and decreased quality of life among middle-aged and older
TAKAHASHI, 1996; MICHELACCI, 1996, HUBER, adults (ATRA, 1995; NEWTON, MOW, GARDNER et al.,
TRATTNIG and LINTNER, 2000; GOMES, 2001). 1997). Excessive loading, anatomical abnormalities, injuries,
Aggrecan is the main PG in the articular cartilage repetitive use, and decreased weight bearing in the joint
composed of the following GAGs: chondroitin, sulfate, and are triggers of this disease (KIVIRANTA, JURVELIN,
keratan sulfate (HASCALL and HASCALL, 1981; CARNEY TAMMI  et  al., 1987; AROKOSKI, KIVIRANTA,

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 Novelli, C., Costa, JBV. and Souza, RR.

JURVELIN  et  al., 1993; WALKER, 1996; NEWTON, Collagen fibrils are composed of protein macromolecules
MOW, GARDNER  et  al., 1997; JORTIKKA, INKINEN and provide articular cartilage with resistance to tension
and TAMMI, 1997). However, it is worth mentioning that (BURSTEIN, BASHIR and GRAY, 2000). Collagen type
osteoarthritis is not necessarily caused only by aging itself II constitutes  85% the  total collagen  content of the total
(NEWTON, MOW, GARDNER et al., 1997). of articular cartilage, and collagen types VI, IX, and XI
Numerous studies have focused on the prevention of constitute the remaining 15% (RIVERO, TEODORO,
osteoarthritis in the elderly, especially because the incidence VELOSA et al., 2000), which are essential for the survival of
of osteoarthritis is expected to increases in the coming decades chondrocytes (KIM, SUH and SONG, 2001).
causing social and economic problems (WALKER, 1996). PGs are macromolecules of high molecular weight
One way to avoid or minimize the effects of osteoarthritis is that consist of a protein covalently attached to one or
through appropriate physical activities. more glycosaminoglycan (GAG) side chains (HUBER,
Several studies have been conducted to indentify the TRATTNIG and LINTNER, 2000; GOMES, 2001), which
influence of different types of physical activities that can are sulfated carbohydrate chains (MICHELLACCI, 1996;
STEVENS and LOWE, 1997). Aggrecan is the main PG in
minimize the deleterious effects of aging on articular cartilage
articular cartilage and is covalently attached to chondroitin
(DEGROOT, VERZIJL, BANK  et  al., 1999; JONES,
sulfate and keratan sulfate chains between the collagen fibrils
GLISSON, HYNES  et  al., 2000; HULDELMAIER,
linked with hyaluronic acid. It presents resistance to loads
GLASER, ENGLMEIER  et  al., 2001; AROKOSKI,
with minimal deformation (GOMES, 2001; CHAMBERS,
KIVIRANTA, JURVELIN  et  al., 1993; BUCKWALTER,
COX, CHONG et al., 2001).
1995; PAP, EBERHARDT, STÜRMER  et  al., 1998;
The main GAGs found in mammals are
HÄÄPALA, AROKOSKI, HYTTINEN  et  al., 1999). The chondroitin‑4‑sulfate, chondroitin-6-sulfate, dermatan
purpose of the literature review conducted is to describe and sulfate, keratan sulfate, heparan sulfate, heparin, and
compare the results of studies on the effects of aging and hyaluronic acid (RUOSLAHTI and YAMAGUCHI, 1997;
various types of physical exercises on the articular cartilage STEVENS and LOWE, 1997).
in order to ascertain their applicability to improve health and Chondrocytes regulate the metabolism of extracellular
quality of life for seniors. matrix by mechanical, physicochemical and electrical stimuli
(TRATTNIG, 1997; POOLE, KOJIMA, YASUDA  et  al.,
2 Material and methods 2001), whose intensity modulate the responses of cellular
functions (SMITH, LIN, TRINDADE et al., 2000).
PubMed (www.pubmed.nl) and MEDLINE databases
Removing any of the biological components of articular
were used to the conduct a literature search using keywords
cartilage can cause damage to it (VASSAN, 1983), movement
without restrictions. In this systematization, papers were
and weight bearing ensure the functionality of the cartilage
searched using the following Keywords: aging, articular
and maintain its cellular properties and mechanical behavior
cartilage, exercise.
(O’CONNOR, ORFORD, and GARDNER, 1988;
BEAUPRÉ, STEVENS, and CARTER, 2000).
3 Results
3.2 Effects of aging
3.1 Structure of articular cartilage The synthetic activity of chondrocytes in all articular
Biochemically, approximately 70% of the articular cartilage cartilage layers declines with age (KARVONEN,
is composed of water and 30% of solids, of which 5-6% are NEGENDANK, TEITGE  et  al., 1994). This decline is
inorganic components (mainly hydroxyapatite), and the essential for maintaining the structure of the extracellular
remaining 25% are organic compounds. Type II collagen matrix and leads to a gradual decrease in its thickness
(KARVONEN, NEGENDANK, TEITGE  et  al., 1994;
constitutes approximately 68% of the organic components,
HULDELMAIER, GLASER, ENGLMEIER et al., 2001).
and the remaining 22% is formed by proteoglycan (KÄÄB,
These variations in the synthesis of cells, which are aging-
GWYN and NÖTZLI, 1998; TRATTNIG, 1997; HUBER,
programmed and beneficial, occur throughout life, and their
TRATTNIG and LINTNER, 2000; BURSTEIN, BASHIR
purpose is to adapt the articular cartilage to mechanical and
and GRAY, 2000; MATYAS, HUANG, CHUNG  et  al.,
chemical needs of the individuals from the fetal period up to
2002). All components of the matrix are continuously
longevity (ROUGHLEY, 2001).
remodeled by the cartilage cells, chondrocytes (WU and The decline in cellular activity in all articular cartilage
HERZOG, 2002). layers can be associated with a decrease in the growth factor
Articular cartilage has three layers: the uppermost (LOESER, 2000; ROUGHLEY, 2001; and apoptosis
superficial layer, with collagen fibrils aligned parallel to the ADAMS and HORTON, 1998), intensified at older age
articular surface, which favors the distribution of pressure; (KARVONEN, NEGENDANK, TEITGE et al., 1994). It is
the middle layer with collagen fibrils oriented perpendicular important to mention that there are variations in the level of
to the articular surface; and the deep layer, also with collagen age-related cartilage degradation, which sets precedents for
fibrils running perpendicular to the articular surface. The histopathologic degeneration (PLAAS, WONG-PALMS and
arrangement of collagen fibrils in the middle and deep layers ROUGHLEY, 1997; ROUGHLEY, 2001; CHAMBERS,
suggests great shock absorbing ability (WALDSCHMIDT, COX, CHONG et al., 2001).
RILLING, KAJDACSY-BALLA  et  al., 1997; WU and Age also produces considerable changes in extracellular
HERZOG, 2002). The chondrocytes are embedded in the matrix components, especially in the amount and structure
matrix in all layers. of PGs (PLAAS, WONG-PALMS and ROUGHLEY, 1997;

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 Aging and physical activity on articular cartilage

ROUGHLEY, 2001). The major mechanical unloading adverse effects and no acceleration in the development of
areas of the articular cartilage undergo an increase in the degenerative joint disease (BUCKWALTER, 1995).
roughness with increasing age (LOESER, 2000) since the With regard to immobilization, its duration and the
content and size of the subunits of PGs (ROUGHLEY amount of weight bearing on the resumption of mobilization
and WHITE, 1980), as well as their synthesis and water are important to determine the response of articular
content (DEGROOT, VERZIJL, BANK  et  al., 1999), are cartilage. According to Hääpala, Arokoski, Hyttinen  et  al.
reduced. Thus, both the hyaluronic acid molecule and the (1999), the loss of GAGs in the uppermost superficial layer
aggrecan molecule reduce in size with age due to proteolytic of articular cartilage in young adult animals does not alter
modifications in the main chain. There is a reduction in the the physiological compressive strength of this material
amount of GAG bound to aggrecan, which explains the during physical exercises after immobilization.
decrease in the hydration of articular cartilage (LOESER, Exercises that excessively compress the articular cartilage
2000) and its lower ability to respond to mechanical loading may bring adverse effects by increasing the internal flow of
Loeser (2000), Huldelmaier, Glaser, Englmeier et al. (2001). water leading to the disruption of the matrix and susceptibility
Aging and a sedentary lifestyle conspire to reduce to degenerative changes (SAH, GRODZINSKY,
mechanical stimulus, which in turn decreases the synthesis PLASS  et  al., 1992; BUCKWALTER, 1995) in addition
of PGs in articular cartilage (DEGROOT, VERZIJL, to the reduction of their PGs in young adult animals
BANK  et  al., 1999). In addition, the ability to repair (AROKOSKI, KIVIRANTA, JURVELIN et al., 1993).
damaged matrix is reduced (LOESER, 2000; ROUGHLEY, A positive response of articular cartilage is mainly
2001). associated to a large extent with the intensity and frequency
With respect to the collagen network of cartilage, there of compressive stimuli inducing increased activity of
is an increase in the number of bonds between collagen chondrocytes, which is identified by its increased nuclear
fibrils (LOESER, 2000), which is possibly associated with volume density per area and thickness of the layers,
increased stiffness and brittleness of the articular cartilage which leads to greater resistance to compression. Another
with aging (BANK, BAYLISS, LAFEBER et al., 1998). consequence is extracellular matrix hydration resulting in
All of these age-related changes that occur in the greater mechanical resistance and elasticity and a consequent
cartilage increase the risk of cartilage damage, but they increase in the number of collagen fibrils which generates
do not necessarily lead to osteoarthritis (KARVONEN, greater resistance to deformation and implies less rigidity.
NEGENDANK, TEITGE  et  al., 1994) because the cell These facts reduce the risk of breakdown of cartilage when it
synthesis is generally able to maintain the morphofunctional is subjected to high mechanical demand.
integrity of cartilage (ADAMS and HORTON, 1998;
HULDELMAIER, GLASER, ENGLMEIER et al., 2001). 4 Discussion
The appreciation of physical activity as a significant health
3.3 Effects of exercises
factor in improvement of quality of life and to promote health
Several studies have shown that the application of has been growing rapidly in recent years, particularly among
constant compressive loading is important to maintain people aging. This is due to the fact that there are many well-
the normal structure of articular cartilage (KIM, SAN, known beneficial effects of exercises on the body. This study
GRODZINSKY  et  al., 1994; BUCKWALTER, 1995; also focused on taking those effects on articular cartilage into
MATYAS, HUANG, CHUNG et al., 2002). consideration, especially in older age groups in which there
It  has  already been  proved  that regular moderate is increased incidence of diseases such as osteoarthritis. It is
physical activity leads to improvements in the known that osteoarthritis is a disease of the musculoskeletal
biomechanical and biological properties of articular system associated with a sedentary lifestyle.
cartilage (KIVIRANTA, TAMMI, JURVELIN  et  al., These statements were corroborated by a similar study
1988) by acting as a chondroprotective (OTTERNESS, that reported a thinning of articular cartilage in aging
ESKRA, BLIVEN  et  al., 1998) increasing the synthesis animals (KARVONEN, NEGENDANK, TEITGE  et  al.,
and concentration of PGs and GAGs (KIVIRANTA, 1994; HULDELMAIER, GLASER, ENGLMEIER  et  al.,
JURVELIN, TAMMI  et  al., 1987; KIVIRANTA, 2001) suggesting that this fact occurs due to the decrease in
TAMMI, JURVELIN et al., 1988; LAMMI, HÄKKINEN, cell activity over time.
PARKKINEN  et  al., 1993; VAN  DEN  HOOGEN, Since osteoarthritis is associated with aging, increasing
VAN DE LEST, VAN WEEREN et al., 1998) and the other life expectancy is a global trend, and urban populations lead
components of cartilage matrix (VISSER, VAKAMOEN, a more sedentary lifestyle, it can be said that osteoarthritis
DEKONING  et  al., 1994; EGRI, BATTISTELLA and can affect large segments of the population influencing the
YOSHINARI, 1999). It also increases cartilage thickness cost of health services and quality of life.
(LAMMI, HÄKKINEN, PARKKINEN  et  al., 1993; Regular physical exercises is an alternative to reverse this
ESPANHA, LAMMI, HYTTINEN et al., 2001). situation since in physical activities with high compressive
Kiviranta, Tammi, Jurvelin  et  al. (1992); Lane and unloading on intra-articular structures, such as running
Buckwalter (1993), Visser, Koning, Lammi  et  al. (1998) (VASSAN, 1983; BIHARI-VARGA, FRAKAS and BIRÓ,
observed changes in the articular cartilage with progressive 1984; VISSER, VAKAMOEN, DEKONING  et  al.,
exercises in young adult animals. They noted an increase in 1994; OTTERNESS, ESKRA, BLIVEN  et  al., 1998;
the concentration and thickness of PGs without changes in PAP, EBERHARDT, STÜRMER  et  al., 1998; EGRI,
its integrity. Subjects of various ages without joint pathology BATTISTELLA and YOSHINARI, 1999), there is an
showed tolerance to prolonged physical training without increase in the synthetic activity of chondrocytes.

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 Novelli, C., Costa, JBV. and Souza, RR.

These results are consistent with previous studies that running, are habits that can prevent or delay the onset of
show that there is a large number of aggrecan molecules in osteoarthritis, which may contribute to the reduction of
areas of higher compressive unloading on weight-bearing public health costs and to the maintenance and improvement
joints, such as those conducted by Wight, Heinegard and and of quality of life.
Hascall (1991), Hardingham, Fosang and Dudhia (1992), Further in vivo experiments with humans are necessary
Yanagishita (1993) and Chambers, Cox, Chong  et  al. since nearly all the studies reviewed were based on animal
(2001). models. Therefore, the findings may not apply to an adequate
In some types of physical activities in which there is total or prescription of physical training loads for humans, as well
partial support in the middle of the body, such as swimming, as determining the optimum frequency in terms of volume,
there is less impact and overload on intra-articular structures intensity, or programming macro, meso, and microcycles
(HARRINSON, HILLMAN and BULSTRODE, 1992; training sessions.
DOWZER, REILLY and CABLE, 1998). In these types of It is known that strength physical activities, such as weight
exercises, great part of the overload is dissipated throughout training, are essential to increase the shock absorption
the limb muscles keeping the joints in constant motion, with by the musculoskeletal system, as well as to stabilize the
no specific points of weight bearing, unlike what occurs joints and allow proper implementation of cyclic or acyclic
during physical activities under gravitational action (KÄÄB, aerobic activities. This issue also deserves further in vivo
GWYN and NÖTZLI, 1998). investigation in humans, especially on aging, considering
It is assumed that the intra-articular overload generated articular cartilage.
by this type of physical activity is mild to moderate and
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Received January 20, 2011

Accepted March 5, 2012

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