Basic Arthritis

Research
Our lab is interested in
the cytokine, growth
factors, extracellular
matrix proteins and
integrins involved in the
chondrocyte signaling
pathways and molecular
mechanisms that
regulate the biology of
chondrocytes and bone
cells.

Figure 2: Dysregulated gene expression profiling in osteoarthritis cartilage

using Affymetrix microarray. Each column represents one sample and
differentially expressed genes are shown in rows.
[Click on image to see enlargement of figure]

Basic research is also

carried out on the
cellular and molecular
mechanisms underlying
chondrocyte
differentiation and
maturation.

We also study global changes in the gene expression in disease tissues utilizing
microarray and bioinformatics (Figure 2).

This is done with nonarthritic and

osteoarthritic cartilage
tissues (Figure 3). We
are also currently
involved in
characterizing the
promoters of
dysregulated genes in
OA with promoter
analyses software to
characterize and study
the influence of
transcription factors on
these genes.
Figure 3: Histology of normal (top panel) and OA (bottom panel) cartilage. The
normal cartilage has smooth articular surface and OA cartilage shows
fibrillation, fissuring of articular surface and also shows clustering of cells in
superficial zone of the cartilage.
[Click on image to see enlargement of figure]

We have demonstrated
important functions for
nitric oxide (NO) and
prostaglandin E2 in the
activation of MAP kinase
signaling, protease
synthesis and cellular
death in chondrocyte
and synovial fibroblast.
Current projects address
the function of novel
proteins such F-spondin
which are not previously
studied in cartilage
metabolism and the
elucidation of their
mechanisms of action

(such as effects on gene

expression,
differentiation of
The fundamental knowledge obtained from these studies is crucial for understanding the pathogenesis and treatment of diseases
such as osteoarthritis and rheumatoid arthritis

Osteoarthritis is a slowly progressive condition that eventually involves all the tissues of a joint. It may be seen
in any joint, but the knee and the hip, the fingers and the hand, and the spine are most commonly affected.
The earliest stage of osteoarthritis is the roughening and fissuring of the normally very smooth gliding surface
of the articular cartilage of a joint. This may progress to partial or complete destruction of this layer, with bone
surfaces grinding against each other. The debris produced causes thickening and inflammation of the soft
tissues, and the bone itself reacts, often leading to the growth of spurs and ridges at the joint margins which
change its shape.
These changes frequently, but not always, cause pain. At first, pain is felt only when the joint is loaded and
moving, but later it is felt at rest and during the night. Involved joints become stiff and may develop instability.
There is increasing impairment of function, disability and handicap.

Figure 1.
Diagrammatic cross-section of a joint affected by osteoarthritis. Note the loss of cartilage, sclerosis and cyst
formation in the underlying bone, osteophytic lipping at the margin and soft tissue reaction.

Figure 2.
Histology of cartilage in early osteoarthritis showing fine fibrillation.
H & E stain, x 80.

Figure 3.
Histological section from an osteoarthritic femoral head showing four regions: exposed bone (with sclerosis and
marrow fibrosis); shelving 'fibrillated' cartilage; 'residual cartilage', and an osteophyte. H & E stain, x4.

Figure 4.
Histological of cartilage and underlying bone in gross osteoarthritis showing shelving finely fibrillated cartilage,
reduced staining, small clumps of chondrocytes and bone sclerosis little alteration in marrow). H & E stain, x
40.

WHY DOES IT DEVELOP?

The initial causes and the reasons for progression of osteoarthritis are not well understood. The earliest
changes are probably within the articular cartilage, and are influenced by abnormal joint loading, recent or old
injuries, hereditary factors and by ageing. Although ageing is strongly associated with the prevalence of
osteoarthritis, the reasons for this are not clear. Osteoarthritis is NOT a 'normal' consequence of ageing.
The tissues involved in osteoarthritis show changes in the metabolism of cells, leading to a complex process of
degradation and repair. This eventually produces changes in structure that are visible on X-ray films.

WHO GETS IT?

Osteoarthritis is seen more commonly with advancing age, although X-ray studies can give a false impression.
Osteoarthritis of the knee is also seen in younger patients, when it is often secondary to earlier injuries of the
joint surfaces, the meniscal cartilages or the ligaments. All of these are more common in men (see Figure 5).
However, after 50 years of age, osteoarthritis of the knee is twice as common in women as in men, suggesting
that hormonal factors may influence its onset (see Figure 6).
The tissues involved in osteoarthritis show changes in the metabolism of cells, leading to a complex process of
degradation and repair. This eventually produces changes in structure that are visible on X-ray films.
Obesity, especially in women, is associated with an increased risk (see Figure 7). Hereditary factors are linked
with osteoarthritis of the knee, as shown by family studies(see Figure 8), but the precise nature of the
relationship is not yet clear.

Figure 5.

Figure 6.

Figure 7.

Figure 8.

WHAT HAPPENS WITH TIME?

Progression of osteoarthritis is usually slow and intermittent; it may take many years to produce serious
symptoms. The condition may remain relatively stable for years, with little or no increase in joint symptoms or
structural changes, or it may even improve for no very obvious reason.

Figure 2. Human knee histology and magnetic resonance imaging.

(A) Histological
representation
of
cartilage
and
subchondral
bone
in
a
normal
and
osteoarthritic
human
knee.
(B) Representations of bone cysts and edema as seen by magnetic resonance imaging in the human osteoarthritic knee femoral condyle. Red arrows indicate
cysts
and
the
red
circle
the
edema.
Figure 2A: Photos by Dr J. Martel-Pelletier. Figure 2B is adapted from reference 17: Raynauld et al. Ann Rheum Dis. 2008;67:683-688. 2008, BMJ Publishing
Group Ltd.

Osteoporosis vs osteoarthritis
The prevalence of both OP and OA is higher in women than men. Risk factors for OA include age, gender (female), genetic
predisposition, mechanical stress and/or joint trauma, and obesity (high BMI). Some of these risk factors are also associated with
OP, yet the opposite weight conditions in the two diseases and the presence of fractures in OP vs OA are some of the conditions
that distinguish the two diseases (Table I).4

Although it is well established that in OP the low bone mass is due to an imbalance in favor of bone resorption over bone formation
(Figure 3, page 394), new hypotheses about OA pathophysiology have been put forward. Hence, OA was re- cently suggested to be
related to an inappropriate attempt at subchondral bone formation leading to cartilage remodeling/ degeneration and
synovitis.20 Moreover, Aspden21 proposed an alternative theory, in which OA could be a pathological growth, not decay, problem
showing excessive and poorly regulated growth of musculoskeletal tissues, with cells possibly reverting to an abnormal
developmental phenotype with a loss of proper function. Hence, (a) mechanism(s) leading to normal tissue formation could be
altered in such a way that tissue integrity is never attained. However, although the latter hypothesis is very attractive and deserves
consideration, many questions still remain to be answered.

C
Ciri2 Umum
Gejala utama adalah nyeri , menyebabkan hilangnya kemampuan dan sering
kekakuan . " Pain" umumnya digambarkan sebagai sakit tajam atau sensasi
terbakar di otot dan tendon terkait . OA dapat menyebabkan suara berderak
( disebut " krepitus " ) ketika sendi yang terkena digerakkan atau disentuh dan
orang-orang mungkin mengalami kejang dan kontraksi otot pada tendon
OA sering mempengaruhi tangan, kaki , tulang belakang , dan berat bantalan sendi
besar , seperti pinggul dan lutut , meskipun dalam teori , setiap sendi dalam tubuh
dapat terpengaruh
In smaller joints, such as at the fingers, hard bony enlargements, called Heberden's
nodes (on the distal interphalangeal joints) and/or Bouchard's nodes (on the
proximal interphalangeal joints), may form, and though they are not necessarily
painful, they do limit the movement of the fingers significantly. OA at the toes leads
to the formation of bunions, rendering them red or swollen. Some people notice
these physical changes before they experience any pain.
The symptoms of OA vary from person to person. Your symptoms will also depend on which joints are affected. OA tends to come
on slowly, over months or even years. The most common symptoms are pain and stiffness of the joints. These feelings are usually
worst after resting or not moving the joint for a while. These symptoms may affect your ability to do normal daily activities, such
as walking, climbing stairs and opening jars.