Let's learn about the anatomy of articular cartilage and its clinical importance in osteoarthritis. Happy Learning!

1. Anatomy of
ARTICULAR CARTILAGE
& Osteoarthritis

2. Articular cartilage
• Highly specialized connective tissue covering bone
epiphyses in synovial joints
• Found at articulating ends of bones within joints of
body
• Hyaline cartilage and is 2 to 4 mm thick
• Function
 Load-bearing material of the joints
 Provide excellent lubrication & great wear characteristic
• Limited capacity for intrinsic healing and repair
 Limited potential of chondrocytes for replication
 Devoid of blood vessels, lymphatics, nerve (Nutrition ?)

3. Structure of articular cartilage
4 zones of articular cartilage
 Superficial zone
 Middle zone
 Deep zone
 Calcified zone
Within each zone, 3 regions can be identified
 Pericellular region
 Territorial region
 Interterritorial region

9. Take home questions
• How is microanatomy of articular cartilage damaged in OA ?
• Why more in older age group ?
• Is Osteoarthritis only a disease of articular cartilage ?
• Why gender differences in OA ?
• Immobilization Vs OA

10. Why OA ?
• Most common chronic musculoskeletal disorder
• Most prevalent cartilage degenerative disease
• Substantial economic burden
• Leading cause of activity limitation & absenteeism
among working-age adults
• Significant decline in function among older individuals.

11. Age related changes
• Dissipation of chondrocytes in the superficial region,
followed by an increase in number of chondrocytes in the
deep layers.
• Decrease in the proteoglycan aggregate numbers within the
ECM. May be a result of
 Proteolytic damage to link protein & glycosaminoglycan
chains
 Increase in partially degraded hyaluronan without newly
synthesized molecules
• Increased mechanical forces exerted on the tissue further
lead to subchondral tissue calcification

12. Pathogenesis of OA
• Trauma causes a microfracture or inflammation
• Slight increase in enzymatic activity which allow formation
of “ wear” particles, engulfed by resident macrophages.
• Production of “wear” particles overwhelms ability of system
to eliminate & they become mediators of inflammation,
stimulating chondrocyte to release degradative enzymes
• Molecules from breakdown of collagen & proteoglycan, also
taken up by synovial macrophages, cause release of
proinflammatory cytokines, like TNFα, IL-1 and IL-6.
• These cytokines bind to chondrocyte receptors leading to
further release of metalloproteinases & inhibition of type II
collagen production, thus increasing cartilage degradation
• Increased water content & decreased proteoglycan content of
ECM, weakening of the collagen network due to decreased
synthesis of type II collagen & increased breakdown of pre-
existing collagen

13. Females Vs OA
• Anatomical factor
 Decrease articular cartilage volume than male
• Previous history of trauma
 Women more cartilage wear, increase ACL injury
• Hormonal factor
 Estrogen beneficial effect in articular cartilage
 Increase proteoglycan in cartilage
• Social factors
 Present for t/t in more advanced stages of OA, so more
pain & disability
 HCW more likely to recommend total joint arthroplasty
for male patient

14. Is Osteoarthritis only a disease of articular cartilage ?
• Initially, osteoarthritis considered disease of articular
cartilage
• Recent research indicate involvement of entire joint
• subchondral bone
• synovium
• menisci
• ligaments, periarticular muscles and nerves

15. Subchondral bone
• Concomitant increase in levels of cartilage oligomeric matrix
protein (COMP) & bone sialoprotein (BSP) in people with
early osteoarthritis
• progressive increase in subchondral bone plate thickness
• formation of new bone at the joint margins – osteophytes
• In osteoarthritic bone tissue, ratio of α1 & α2 chains of type I
collagen varied between 4:1 & 17:1, and this appears to be
responsible for abnormal mineralization pattern
 In normal bone, type I collagen consist of heterotrimer
of α1 & α2 chains at an average ratio of 2.4:1.

16. • Synovial membrane of osteoarthritic joints commonly
exhibits hyperplasia of lining cell layer occasionally
accompanied by focal infiltration of lymphocytes &
monocytes in sublining layers
• Meniscal degeneration : menisci appear torn, fissured,
fragmented, macerated or completely destroyed

17. • The loss of articular cartilage thought to be primary change,
but a combination of cellular changes & biomechanical
stresses causes several secondary changes, including
 subchondral bone remodeling,
 formation of osteophytes
 development of bone marrow lesions
 change in the synovium, joint capsule, ligaments &
periarticular muscles
 meniscal tears and extrusion

18. Immobility Vs OA
• Mechanical load necessary for cartilage homeostasis.
• Induces fluid movement between cartilage & synovial
fluid, that helps in diffusion of molecules across cartilage
thus facilitating its nutrition
• Decrease protease (MMP-3, ADAMTS-5) expression in
human chondrocytes
• Increases proteoglycan (aggrecan)
• Inhibits IL-1 & TNF-α induced inflammatory &
catabolic responses
• immobilization leads to joint damage

20. Normoxia Vs hyoxia
• Since cartilage is an avascular tissue, chondrocytes live in a
hypoxic environment
• Hypoxia displays a protective effect on cartilage
• Lower basal synthesis & release of MMP-1, MMP-13
• Lower generation of type II collagen cleavage fragments
• HIF-1α promote chondrocyte function and survival
• Gene encoding HIF-1α, Epas1 expressed in cartilage
• Deletion of Epas1 gene in cartilaginous growth plate
associated with chondrocyte apoptosis
• Inhibitor of HIF-1,intraarticular injection promote
cartilage degradation & osteophyte formation

21. References
• Sophia Fox AJ, Bedi A, Rodeo SA. The basic science
of articular cartilage: structure, composition, and
function. Sports Health. 2009;1(6):461-468.
• Houard X, Goldring MB, Berenbaum F. Homeostatic
mechanisms in articular cartilage and role of
inflammation in osteoarthritis. Curr Rheumatol
Rep. 2013;15(11):375.

22. THANK YOU