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Curriculum Vitae

Name :
Andri Reza Rahmadi, MD, Internist & Rheumatologist , M.Med

Education :
Medical Doctor graduated 1997 F.Med UNPAD Bandung
Master of Medicine graduated 2003 UGM Yogyakarta
Internal Medicine specialist graduated 2008 F.Med UNPAD
Bandung
Rheumatology consultant graduated 2013 F.Med UNPAD/RSHS
Bandung

Fellow :
IDI, PAPDI, IRA
PATHOPHYSIOLOGY OF OSTEOARTHRITIS

Andri Reza Rahmadi, MD, Internist & Rheumatologist, M.Med


Introduction
Definition :

Osteoarthritis (OA) is a degenerative disease of


diarthrodial (synovial) joints, characterized by

Breakdown of articular cartilage

and proliferative changes of surrounding bones


Osteoarthritis : Degenerative Disease
Osteoarthritis
Past and New

Past :
Non Inflamation
Wear and Tear

New :
Mediator inflamation
Multifactorial etiology
Epidemiology
Hasan Sadikin Hospital
Bandung

2007 in Rheumatology Clinic


1297 patients, 74,48% OA

2012 in Rheumatology Clinic


3986 patients, 64,91% OA
Up to Date

Until late 20th century 21st century


A passive consequence A cell-driven mechanism
of tear and wear based on soluble mediators

A pro-inflammatory
A degenerative disease disease

A cartilage disease A multiple-tissue disease

A biological challenge open


An inevitable fate to therapeutic intervention
Normal Cartilage Matrix
Cartilage

Avascular
Low Oxigen
Metabolism : glycolysis anaerob, lactic acid
Ph : 7,1 7,2
Nutrition and Water : from Synovium and
Subchondran bone
Difusion process
Cartilage Component

Chondrocyte, produce :
Collagen
Proteoglycan

Matrix exracellular :
Water 65%
Colagen type II, IV, IX, XVI and Proteoglycan 15-
25%
Proteoglycan = Agrecan

Glucosaminoglycan

Chondroitin sulfate

Ceratan sulfate

Hyaluronic acid
Turnover :

Collagen : half life 100 year

Agrecan : half life 3-24 year


Osteoarthritis Cartilage
Clasification

PRIMARY
Unknown etiology
Degenerative
Genetic

SECONDARY
Known etiology
Trauma
Overuse
Genetic

Scientist have discovered 11 pieces of genetic


code linked

Half OA patient have it

The one with the strongest effect was


situated in the region GNL 3 gene which
produces a protein with an important role in
cell maintenance
Mechanical Aspect

Obese
Over use
Weight forcess
Stairs
Climb
Sport
Accident
Trauma
Mechanical Aspect
Pathophysiology OA
Interaction

Chondrocyte and Matrix Intracelular


Mediated by Integrin in cell surface
Normal Condition : homeostatis
Abnormal condition : more deragradation
Abnormal signaling by Integrin
Produce degradative enzyme : chondrocyte
Dominant enzyme : metaloproteinase (MMP)
Proteinase Enzyme

Metallo proteinase (Dominant in OA)

Serine proteinase

Cystein proteinase

Aspartat proteinase.
Metaloproteinase :

Collagenase
Gelatinase
Stromeolysine

Other : A Disintegrin and metaloproteinase


with Trombospondin Motifs type-1 (ADAMTs)
Process

Trauma Cell collagen damage


Stimuli for macrophage in synovial line cell
Active macrophage in synovial line
Produce inflamation mediators :
IL 1
IL 6
IL 17
TNF -
Cytokine pro inflamation

IL-1 : damage chondrocyte

IL-1 receptor in cell surface in chondrocyte

IL -1 receptor antagonist (IL-1 ra) produced


from synovial tissue to inhibit this reacti0n

Balance chondrogenesis homeostasis


Pathology : Inflamation
Inhibitor Mechanism

New cell for regeneration : Chondroblast


Proliferation to chondrocyte
Condroblast produce inhibitory enzyme :
Tissue inhibitor of metalloproteinase (TIMPs) :
TIMP-1, TIMP-2, TIMP-3, and TIMP-4.
In OA patients : Low TIMP level
Growth Factor in OA

Produced by Cell Synovium + Chondrocyte


Compensation : active if protease enzyme
Help proliferation of chondroblast
Side effect : subchondral bone growth
Produce Osteophyte
Enhtesytis
Inflamation Pain
Growth Factor :

Transforming Growth Factor (TGF)

Insuline Growth Factor (IGF)

Fibroblast Growth Factor (FGF)


Free Radical in OA

Stress Oxidative from Super Oxyde reaction


Go direct to the Inside to the chondrocyte cell
Damage mithochodrial cell
Faster Apoptosis process
Ageing
Damage chondrocyte cell OA
Activate inflamation cascade
Summary

Osteoarthritis is adisease with low level


inflamation
Until now it is not known mechanism
OA have some Multifactorial Risk Factors
It s need further research in OA to find other
mechanism

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